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Sample records for system atrophy diagnosed

  1. [Value of anal sphincter electromyography, orthostatic hypotension and dizziness in diagnosing multiple system atrophy].

    PubMed

    Wang, Han; Cui, Li-Ying; Du, Hua; Li, Ben-Hong; Liu, Ming-Sheng; Guan, Yu-Zhou

    2008-12-01

    To explore the value of anal sphincter electromyography (ASEMG), orthostatic hypotension (OH), and dizziness in diagnosing multiple system atrophy (MSA). The characteristics of ASEMG and OH were compared among patients with dizziness (MSA and non-MSA), patients without OH (MSA and non-MSA), and patients with probable MSA (OH and non-OH). Totally 476 patients underwent ASEMG examinations. Dizziness was the onset symptom in 69 patients. Between the MSA group and non-MSA group, the mean duration of dizziness [(14.6 +/- 2.1) vs. (12.8 +/- 2.0) ms, P < 0.01] and satellite potential occurrence rate [(22.7 +/- 11.8)% vs. (12.2 +/- 8.9)% , P < 0.01] were significantly different, while the OH rate (84.6% vs. 55.2% ) and the difference of the blood pressure between standing and supine positions were not significantly different. In 162 patients with symptom of dizziness, the mean duration of dizziness [(15.3 +/- 2.7) vs. (12.8 +/- 1.9) ms, P < 0.001], satellite potential occurrence rate [(25.4 +/- 12.8)% vs. (13.5 +/- 10.4)%, P < 0.001] , and difference of the diastolic blood pressure [(18.5 +/- 17.0) vs. (11.7 +/- 12.7) mmHg, P < 0.05] were significantly different between the MSA group and non-MSA group, while the normal rate of blood pressure at standing position (60% vs. 41.9%) and the difference of systolic blood pressure were not significantly different. In 146 patients with abnormal blood pressure at standing and supine positions, the mean duration of dizziness [(15.0 +/- 2.4) vs. (12.8 +/- 1.7) ms, P < 0.001] and satellite potential occurrence rate [(22.0 +/- 12.2)% vs. (10.6 +/- 8.5)%, P < 0.001] were significantly different between the MSA group (n = 61) and non-MSA group (n = 85). In 125 patients with probable MSA, the mean duration of dizziness [(15.5 +/- 2.4) vs. (15.9 +/- 2.2) ms, P > 0.05] and satellite potential occurrence rate [(24.3 +/- 12.6)% vs. (22.7 +/- 12.4)%, P > 0.05] were not significantly different between those with OH and those without OH. The

  2. Multiple System Atrophy (MSA)

    MedlinePlus

    Multiple system atrophy (MSA) Overview By Mayo Clinic Staff Multiple system atrophy (MSA) is a rare, degenerative neurological disorder ... progresses gradually and eventually leads to death. Multiple system atrophy care at Mayo Clinic . Mayo Clinic Footer ...

  3. Multiple System Atrophy (MSA)

    MedlinePlus

    ... to-day activities Vocal cord paralysis, which makes speech and breathing difficult Increased difficulty swallowing People typically live about seven to 10 years after multiple system atrophy symptoms first appear. However, the ...

  4. Mortality and differential diagnoses of villous atrophy without coeliac antibodies.

    PubMed

    Schiepatti, Annalisa; Biagi, Federico; Fraternale, Giacomo; Vattiato, Claudia; Balduzzi, Davide; Agazzi, Simona; Alpini, Claudia; Klersy, Catherine; Corazza, Gino R

    2017-01-11

    Villous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies. Clinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed. Between September 1999 and June 2015, 274 patients were diagnosed with VA. A total of 260 patients were also positive to coeliac antibodies; the other 14 had VA, but no IgA endomysial antibodies: five had common variable immunodeficiency, three had dermatitis herpetiformis, two had IgA deficiency associated with CD, one had abdominal lymphoma, one had unclassified sprue, one had olmesartan-associated enteropathy and one had seronegative CD. Mortality was 6.0 deaths per 100 person years (95% confidence interval: 2.2-16) in patients with VA but negative coeliac antibodies, whereas only 0.2 deaths per 100 person years (95% confidence interval: 0.1-0.6) occurred in coeliac patients. Patients with VA and negative endomysial antibodies are rare. However, these forms of VA identify specific causes that can be diagnosed. These patients are affected by a very high mortality.

  5. Genetics Home Reference: multiple system atrophy

    MedlinePlus

    ... Management Genetic Testing (1 link) Genetic Testing Registry: Shy-Drager syndrome Other Diagnosis and Management Resources (1 ... progressive autonomic failure with multiple system atrophy SDS Shy-Drager syndrome sporadic olivopontocerebellar atrophy Related Information How ...

  6. Multiple system atrophy

    MedlinePlus

    ... nervous system that controls important functions such as heart rate, blood pressure, and sweating. ... A pacemaker that is programmed to stimulate the heart to beat at ... blood pressure for some people. Constipation can be treated with ...

  7. [Evaluation of Gastric Atrophy. Comparison between Sidney and OLGA Systems].

    PubMed

    Ramírez-Mendoza, Pablo; González-Angulo, Jorge; Angeles-Garay, Ulises; Segovia-Cueva, Gustavo Adolfo

    2008-01-01

    histopathologic identification of atrophy and metaplasia is decisive to stop the way of gastritis?carcinoma in patients with chronic gastritis. to compare diagnostic concordance between Sidney system and the operative Link on Gastritis Assessment (OLGA) system. 120 consecutive biopsies were analyzed by general pathologists according to the Sidney system. All of them were evaluated by a second pathologist who used OLGA System. We employed kappa index to evaluate diagnostic concordance between the classifications. the clinical picture includes dyspepsia (94 %), abdominal pain (50 %), gastroesophageal reflux (30 %), bleed of the upper digestive system (24 %), and presence of Helicobacter pylori (47.5 %). Four were diagnosed as atrophy by Sidney system and 26 cases with atrophy by OLGA system. The concordance between two classifications systems was too low (p = 0.05). the atrophy diagnosis, between systems, had low concordance. The description of metaplastic atrophy in the OLGA system represents the only one difference. The non-metaplastic atrophy is the same for both classifications. Therefore, the general pathologist should include this evaluation more consistently using OLGA system.

  8. Models of Multiple System Atrophy

    PubMed Central

    Fellner, Lisa; Wenning, Gregor K.; Stefanova, Nadia

    2016-01-01

    Multiple system atrophy (MSA) is a predominantly sporadic, adult-onset, fatal neurodegenerative disease of unknown etiology. MSA is characterized by autonomic failure, levodopa-unresponsive parkinsonism, cerebellar ataxia and pyramidal signs in any combination. MSA belongs to a group of neurodegenerative disorders termed α-synucleinopathies, which also include Parkinson’s disease and dementia with Lewy bodies. Their common pathological feature is the occurrence of abnormal α-synuclein positive inclusions in neurons or glial cells. In MSA, the main cell type presenting aggregates composed of α-synuclein are oligodendroglial cells. This pathological hallmark, also called glial cytoplasmic inclusions (GCIs), is associated with progressive and profound neuronal loss in various regions of the brain. The development of animal models of MSA is justified by the limited understanding of the mechanisms of neurodegeneration and GCIs formation, which is paralleled by a lack of therapeutic strategies. Two main types of rodent models have been generated to replicate different features of MSA neuropathology. On one hand, neurotoxin-based models have been produced to reproduce neuronal loss in substantia nigra pars compacta and striatum. On the other hand, transgenic mouse models with overexpression of α-synuclein in oligodendroglia have been used to reproduce GCIs-related pathology. This chapter gives an overview of the atypical Parkinson’s syndrome MSA and summarizes the currently available MSA animal models and their relevance for pre-clinical testing of disease-modifying therapies. PMID:24338664

  9. Cognitive impairment in multiple system atrophy

    PubMed Central

    Stankovic, Iva; Krismer, Florian; Jesic, Aleksandar; Antonini, Angelo; Benke, Thomas; Brown, Richard G.; Burn, David J.; Holton, Janice L.; Kaufmann, Horacio; Kostic, Vladimir S.; Ling, Helen; Meissner, Wassilios G.; Poewe, Werner; Semnic, Marija; Seppi, Klaus; Takeda, Atsushi; Weintraub, Daniel; Wenning, Gregor K.

    2014-01-01

    Consensus diagnostic criteria for multiple system atrophy consider dementia as a non-supporting feature, despite emerging evidence demonstrating that cognitive impairments are an integral part of the disease. Cognitive disturbances in multiple system atrophy occur across a wide spectrum from mild single domain deficits to impairments in multiple domains and even to frank dementia in some cases. Frontal-executive dysfunction is the most common presentation, while memory and visuospatial functions may also be impaired. Imaging and neuropathological findings support the concept that cognitive impairments in MSA originate from striatofrontal deafferentation with additional contributions from intrinsic cortical degeneration and cerebellar pathology. Based on a comprehensive evidence-based review we here propose future avenues of research that may ultimately lead to diagnostic criteria for cognitive impairment and dementia associated with multiple system atrophy. PMID:24753321

  10. Restless legs syndrome in multiple system atrophy.

    PubMed

    Ghorayeb, Imad; Dupouy, Sandrine; Tison, François; Meissner, Wassilios G

    2014-12-01

    The purpose of the study was to evaluate the frequency of restless legs syndrome in 30 patients with multiple system atrophy. Eight patients complained from restless legs syndrome, their severity score was 19.4 ± 4.1. Pittsburgh Sleep Quality Index scores were significantly higher in patients with restless legs syndrome than those without (9.3 ± 3.7 vs. 4.8 ± 2.9, p = 0.00165). Periodic limb movements were found in 75% of patients with restless legs syndrome. Restless legs syndrome is more prevalent in multiple system atrophy as compared to the acknowledged prevalence in the general population.

  11. MAPT haplotype diversity in multiple system atrophy

    PubMed Central

    Labbé, Catherine; Heckman, Michael G.; Lorenzo-Betancor, Oswaldo; Murray, Melissa E.; Ogaki, Kotaro; Soto-Ortolaza, Alexandra I.; Walton, Ronald L.; Fujioka, Shinsuke; Koga, Shunsuke; Uitti, Ryan J.; van Gerpen, Jay A.; Petersen, Ronald C.; Graff-Radford, Neill R.; Younkin, Steven G.; Boeve, Bradley F.; Cheshire, William P.; Low, Phillip A.; Sandroni, Paola; Coon, Elizabeth A.; Singer, Wolfgang; Wszolek, Zbigniew K.; Dickson, Dennis W.; Ross, Owen A.

    2016-01-01

    Introduction Multiple system atrophy (MSA) is a rare progressive neurodegenerative disorder. MSA was originally considered exclusively sporadic but reports of association with genes such as SNCA, COQ2 and LRRK2 have demonstrated that there is a genetic contribution to the disease. MAPT has been associated with several neurodegenerative diseases and we previously reported a protective association of the MAPT H2 haplotype with MSA in 61 pathologically confirmed cases. Methods In the present study, we assessed the full MAPT haplotype diversity in MSA patients using six MAPT tagging SNPs. We genotyped a total of 127 pathologically confirmed MSA cases, 86 patients with clinically diagnosed MSA and 1312 controls. Results We identified four significant association signals in our pathologically confirmed cases, two from the protective haplotypes H2 (MSA:16.2%, Controls:22.7%, p=0.024) and H1E (MSA:3.0%, Controls:9.0%, p=0.014), and two from the rare risk haplotypes H1x (MSA:3.7%, Controls:1.3%, p=0.030) and H1J (MSA:3.0%, Controls:0.9%, p=0.021). We evaluated the association of MSA subtypes with the common protective H2 haplotype and found a significant difference with controls for MSA patients with some degree of MSA-C (MSA-C or MSA-mixed), for whom H2 occurred in only 8.6% of patients in our pathologically confirmed series (P<0.0001). Conclusions Our findings provide further evidence that MAPT variation is associated with risk of MSA. Interestingly, our results suggest a greater effect size in the MSA-C compared to MSA-P for H2. Additional genetic studies in larger pathologically confirmed MSA series and meta-analytic studies will be needed to fully assess the role of MAPT and other genes in MSA. PMID:27374978

  12. [Susceptibility gene in multiple system atrophy (MSA)].

    PubMed

    Tsuji, Shoji

    2014-01-01

    To elucidate molecular bases of multiple system atrophy (MSA), we first focused on recently identified MSA multiplex families. Though linkage analyses followed by whole genome resequencing, we have identified a causative gene, COQ2, for MSA. We then conducted comprehensive nucleotide sequence analysis of COQ2 of sporadic MSA cases and controls, and found that functionally deleterious COQ2 variants confer a strong risk for developing MSA. COQ2 encodes an enzyme in the biosynthetic pathway of coenzyme Q10. Decreased synthesis of coenzyme Q10 is considered to be involved in the pathogenesis of MSA through decreased electron transport in mitochondria and increased vulnerability to oxidative stress.

  13. Multiple System Atrophy: Genetic or Epigenetic?

    PubMed Central

    Sturm, Edith

    2014-01-01

    Multiple system atrophy (MSA) is a rare, late-onset and fatal neurodegenerative disease including multisystem neurodegeneration and the formation of α-synuclein containing oligodendroglial cytoplasmic inclusions (GCIs), which present the hallmark of the disease. MSA is considered to be a sporadic disease; however certain genetic aspects have been studied during the last years in order to shed light on the largely unknown etiology and pathogenesis of the disease. Epidemiological studies focused on the possible impact of environmental factors on MSA disease development. This article gives an overview on the findings from genetic and epigenetic studies on MSA and discusses the role of genetic or epigenetic factors in disease pathogenesis. PMID:25548529

  14. Diagnosable systems for intermittent faults

    NASA Technical Reports Server (NTRS)

    Mallela, S.; Masson, G. M.

    1978-01-01

    The fault diagnosis capabilities of systems composed of interconnected units capable of testing each other are studied for the case of systems with intermittent faults. A central role is played by the concept of t(i)-fault diagnosability. A system is said to be t(i)-fault diagnosable when it is such that if no more than t(i) units are intermittently faulty then a fault-free unit will never be diagnosed as faulty and the diagnosis at any time is at worst incomplete. Necessary and sufficient conditions for t(i)-fault diagnosability are proved, and bounds for t(i) are established. The conditions are in general more restrictive than those for permanent-fault diagnosability. For intermittent faults there is only one testing strategy (repetitive testing), and consequently only one type of intermittent-fault diagnosable system.

  15. Role of the "immersion technique" in diagnosing celiac disease with villous atrophy limited to the duodenal bulb.

    PubMed

    Cammarota, Giovanni; Cesaro, Paola; La Mura, Rossella; Martino, Antonio; Cazzato, Alessia; Miele, Luca; Lupascu, Andrea; Vecchio, Fabio M; Larocca, Luigi M; Grieco, Antonio; Gasbarrini, Giovanni

    2007-07-01

    To investigate if the so-called immersion technique during upper endoscopy may be helpful to predict patterns of villous atrophy restricted to the duodenal bulb. Patients with celiac disease may have a patchy distribution of duodenal villous atrophy. In some cases, mucosa of duodenal bulb may be the only intestinal area involved. The immersion technique is a novel procedure that allows visualizing duodenal villi directly during endoscopy. With this prospective study, the immersion duodenoscopy was performed in 67 celiac subjects to investigate their duodenal villous pattern. Villi were evaluated both in the first and in the second duodenal segment and judged as present or absent (flat mucosa). Results were compared with histology as reference. Among celiac subjects, 49 were newly diagnosed and 18 previously diagnosed celiac patients. Four (8%) newly diagnosed and 7 (39%) previously diagnosed celiac subjects had an extension of the villous atrophy (flat mucosa) limited to the duodenal bulb. The sensitivity, specificity, and positive and negative predictive values of the immersion-based duodenal investigation in predicting areas of duodenal villous atrophy was always 100%. Immersion technique may be useful for directing duodenal biopsies in celiac subjects with a patchy distribution of villous atrophy. This procedure can avoid blinded sampling of the duodenal mucosa and enhance the diagnostic yield.

  16. Short article: Mortality and differential diagnoses of villous atrophy without coeliac antibodies.

    PubMed

    Schiepatti, Annalisa; Biagi, Federico; Fraternale, Giacomo; Vattiato, Claudia; Balduzzi, Davide; Agazzi, Simona; Alpini, Claudia; Klersy, Catherine; Corazza, Gino R

    2017-05-01

    Villous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies. Clinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed. Between September 1999 and June 2015, 274 patients were diagnosed with VA. A total of 260 patients were also positive to coeliac antibodies; the other 14 had VA, but no IgA endomysial antibodies: five had common variable immunodeficiency, three had dermatitis herpetiformis, two had IgA deficiency associated with CD, one had abdominal lymphoma, one had unclassified sprue, one had olmesartan-associated enteropathy and one had seronegative CD. Mortality was 6.0 deaths per 100 person years (95% confidence interval: 2.2-16) in patients with VA but negative coeliac antibodies, whereas only 0.2 deaths per 100 person years (95% confidence interval: 0.1-0.6) occurred in coeliac patients. Patients with VA and negative endomysial antibodies are rare. However, these forms of VA identify specific causes that can be diagnosed. These patients are affected by a very high mortality.

  17. In vitro models of multiple system atrophy.

    PubMed

    Stefanova, Nadia; Reindl, Markus; Poewe, Werner; Wenning, Gregor K

    2005-08-01

    alpha-Synuclein represents the major constituent of oligodendroglial cytoplasmic inclusions, the hallmark lesion of multiple system atrophy (MSA), a progressive disorder that is associated with selective degenerative cell loss in basal ganglia, cerebellum, brainstem, and spinal cord. The role of abnormal alpha-synuclein aggregation in oligodendroglial cells is still obscure, in particular, whether alpha-synuclein might impair oligodendroglial and, secondarily, neuronal integrity of those cells in the diseased brain. In an attempt to answer some of these questions, we have developed an "in vitro model of MSA" by expressing the wild-type or C-terminally truncated form of alpha-synuclein in glial cell cultures. With this simplified system, we have demonstrated that alpha-synuclein significantly affects the survival of glia and its vulnerability to environmental stress, which might represent a major step in the pathogenesis of MSA.

  18. Anhidrosis in multiple system atrophy: a preganglionic sudomotor dysfunction?

    PubMed

    Donadio, Vincenzo; Nolano, Maria; Elam, Mikael; Montagna, Pasquale; Provitera, Vincenzo; Bugiardini, Enrico; Baruzzi, Agostino; Santoro, Lucio; Liguori, Rocco

    2008-04-30

    Anhidrosis occurs in the majority of multiple system atrophy (MSA) patients but the underlying site of lesion is not well established. We describe three patients with long-standing MSA and anhidrosis diagnosed on the basis of a thermoregulatory sweating test. In biopsies of anhidrotic skin, immunofluorescence analysis disclosed a well preserved postganglionic sudomotor innervation in all three patients supporting the hypothesis of a preganglionic nerve fiber lesion underlying their anhidrosis. Postganglionic sudomotor fiber integrity was also confirmed by normal electrodermal responses in one patient, whereas such responses and microneurographically detectable skin sympathetic nerve activity were absent in the other two MSA patients, suggesting a functional inactivity of structurally intact postganglionic sympathetic skin fibers.

  19. Towards translational therapies for multiple system atrophy

    PubMed Central

    Kuzdas-Wood, Daniela; Stefanova, Nadia; Jellinger, Kurt A.; Seppi, Klaus; Schlossmacher, Michael G.; Poewe, Werner; Wenning, Gregor K.

    2014-01-01

    Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disorder of uncertain etiopathogenesis manifesting with autonomic failure, parkinsonism, and ataxia in any combination. The underlying neuropathology affects central autonomic, striatonigral and olivopontocerebellar pathways and it is associated with distinctive glial cytoplasmic inclusions (GCIs, Papp-Lantos bodies) that contain aggregates of α-synuclein. Current treatment options are very limited and mainly focused on symptomatic relief, whereas disease modifying options are lacking. Despite extensive testing, no neuroprotective drug treatment has been identified up to now; however, a neurorestorative approach utilizing autologous mesenchymal stem cells has shown remarkable beneficial effects in the cerebellar variant of MSA. Here, we review the progress made over the last decade in defining pathogenic targets in MSA and summarize insights gained from candidate disease-modifying interventions that have utilized a variety of well-established preclinical MSA models. We also discuss the current limitations that our field faces and suggest solutions for possible approaches in cause-directed therapies of MSA. PMID:24598411

  20. Novel Therapeutic Approaches in Multiple System Atrophy

    PubMed Central

    Palma, Jose-Alberto; Kaufmann, Horacio

    2014-01-01

    Multiple system atrophy (MSA) is a sporadic, adult onset, relentlessly, progressive neurodegenerative disease characterized by autonomic abnormalities associated with parkinsonism, cerebellar dysfunction, pyramidal signs, or combinations thereof. Treatments that can halt or reverse the progression of MSA have not yet been identified. MSA is neuropathologically defined by the presence of α-synuclein–containing inclusions, particularly in the cytoplasm of oligodendrocytes (glial cytoplasmic inclusions, GCIs), which are associated with neurodegeneration. The mechanisms by which oligodendrocytic α-synuclein inclusions cause neuronal death in MSA are not completely understood. The MSA neurodegenerative process likely comprise cell-to-cell transmission of α-synuclein in a prion-like manner, α-synuclein aggregation, increased oxidative stress, abnormal expression of tubulin proteins, decreased expression of neurotrophic factors, excitotoxicity and microglial activation, and neuroinflammation. In an attempt to block each of these pathogenic mechanisms, several pharmacologic approaches have been tried and shown to exert neuroprotective effects in transgenic mouse or cellular models of MSA. These include sertraline, paroxetine, and lithium, which hamper arrival of α-synuclein to oligodendroglia; rifampicin, lithium, and non-steroidal anti-inflamatory drugs, which inhibit α-synuclein aggregation in oligodendrocytes; riluzole, rasagiline, fluoxetine and mesenchimal stem cells, which exert neuroprotective actions; and minocycline and intravenous immunoglobulins, which reduce neuroinflammation and microglial activation. These and other potential therapeutic strategies for MSA are summarized in this review. PMID:24928797

  1. System diagnosability using triplet assertion

    SciTech Connect

    Lombardi, F.

    1982-01-01

    A new technique for system diagnosability is presented. It is based on a triplet assertion strategy to overcome the asymmetric invalidation and the requirement of a central test controller. The basic characteristics of the triplet assertion are generalized to higher networks. The application of this technique to parallel processing is outlined. 24 references.

  2. Diagnosability issues in multiprocessor systems

    SciTech Connect

    Raghavan, V.

    1989-01-01

    In a seminal paper on fault diagnosis, Preparata, Metze, and Chien introduced a graph-theoretical model. Barsi, Grandoni, and Maestrini relaxed some constraints in this model to create a different model for fault diagnosis. Both these models have become the subject of intense research in the past two decades. A major open problem for these models is the question of sequential t-diagnosability-Given an arbitrary system of units and that there are no more than t faulty units in it, can we always identify at least one faulty unit The author shows that this problem is co-NP complete in both models. Recent research has shown that there are polynomial time algorithms to find the maximum number of faulty units a system can withstand and still identify all of them from a single collection of test results. He presents improved algorithms to solve this problem in both models. Using the letters n,m, and {tau} to denote the number of units, the number of tests, and the maximum number of faulty units respectively, our results can be summarized as follows: in the model of Barsi, Grandoni, and Maestrini, the algorithm has a time complexity of O(n{tau}{sup 2}/log{tau}) improving on the currently known O(n{tau}{sup 2}); in the model of Preparata, Metze, and Chien, the algorithm has a complexity of O(n{tau}{sup 2.5}) improving on the currently known O(mn{sup 1.5}). He also presents related results in the latter model, which suggest the possibility of reducing the complexity even further. Finally, he develops a general scheme for characterizing diagnosable systems. Using this scheme, he solves the open problem of characterizing t/s and sequentially t-diagnosable systems. The characterizations are then used to rederive some known results.

  3. Progressive Retinal Structure Abnormalities in Multiple System Atrophy

    PubMed Central

    Mendoza-Santiesteban, Carlos E.; Palma, Jose-Alberto; Martinez, Jose; Norcliffe-Kaufmann, Lucy; Hedges, Thomas R.; Kaufmann, Horacio

    2015-01-01

    Background Objective measures of disease progression that can be used as end-points in clinical trials of multiple system atrophy are necessary. We studied retinal thickness in patients with multiple system atrophy, and assessed changes over time to determine its usefulness as imaging biomarker of disease progression. Methods Cross sectional study including 24 patients with multiple system atrophy, 20 patients with Parkinson disease (PD) and 35 controls; followed by a longitudinal study of 13 multiple system atrophy (MSA) patients. Patients were evaluated with high definition-optical coherence tomography and the Unified Multiple System Atrophy Rating Scale. Evaluations were performed at baseline and at consecutive follow-up visits for up to 26 months. Results MSA subjects had normal visual acuity and color discrimination. Compared to controls, retinal nerve fiber layer (p=0.008 and p=0.001) and ganglion cell complex (p=0.013 and p=0.001) thicknesses were reduced in multiple system atrophy and in PD. No significant differences between MSA and PD were found. Over time, in patients with MSA, there was a significant reduction of the retinal nerve fiber layer and ganglion cell complex thicknesses, with estimated annual average losses of 3.7 μm and 1.8 μm respectively. Conclusions Visually asymptomatic MSA patients exhibit progressive reductions in the thickness of the retinal nerve fiber layer and, to a lesser extent, in the macular ganglion cell complex, which can be quantified by high-definition optical coherence tomography. Specific patterns of retinal nerve fiber damage could be a useful imaging biomarker of disease progression in future clinical trials. PMID:26359930

  4. Optical coherence tomography in pediatric patients: a feasible technique for diagnosing celiac disease in children with villous atrophy.

    PubMed

    Masci, E; Mangiavillano, B; Barera, G; Parma, B; Albarello, L; Mariani, A; Doglioni, C; Testoni, P A

    2009-09-01

    Celiac disease is a common condition with many atypical manifestations, where histology serves as the "gold standard" for diagnosis. A useful new technique, optical coherence tomography, can depict villous morphology in detail, using light waves. This study examined the correlation between the sensitivity and specificity of optical coherence tomography in pediatric patients undergoing esophago-gastro-duodenoscopy for the diagnosis of celiac disease. A total of 134 children were prospectively enrolled, 67 with a serological suspicion of celiac disease (group 1) and 67 with negative histology for celiac disease (group 2). During a diagnostic esophago-gastro-duodenoscopy we acquired multiple images and films in the four quadrants of the second part of the duodenum, and biopsies were taken in the area where optical coherence tomography had been done. Three patterns of villous morphology were considered: pattern 1=no atrophy (types 0, 1 or 2 of the Marsh classification); pattern 2=mild atrophy (type 3a or 3b); pattern 3=marked atrophy (type 3c). The diagnosis of celiac disease was histologically confirmed in all 67 children with positive antiendomysium and/or antitransglutaminase antibodies. Optical coherence tomography correlated with pattern 1 histology in 11/11 cases, pattern 2 in 30/32 (93.8%) and pattern 3 in 22/24 (91.6%). Sensitivity and specificity were 82% and 100%. In the control group there was 100% concordance between optical coherence tomography and histology. The overall concordance between optical coherence tomography and histology in determining patchy lesions was 75%. Optical coherence tomography could be a helpful diagnostic tool in children with mild or marked villous atrophy for diagnosing celiac disease during upper gastrointestinal (GI) endoscopy, avoiding biopsies. However, duodenal biopsies are mandatory if the optical coherence tomography shows normal villous morphology in patients with positive antibodies.

  5. Using visual rating to diagnose dementia: a critical evaluation of MRI atrophy scales.

    PubMed

    Harper, Lorna; Barkhof, Frederik; Fox, Nick C; Schott, Jonathan M

    2015-11-01

    Visual rating scales, developed to assess atrophy in patients with cognitive impairment, offer a cost-effective diagnostic tool that is ideally suited for implementation in clinical practice. By focusing attention on brain regions susceptible to change in dementia and enforcing structured reporting of these findings, visual rating can improve the sensitivity, reliability and diagnostic value of radiological image interpretation. Brain imaging is recommended in all current diagnostic guidelines relating to dementia, and recent guidelines have also recommended the application of medial temporal lobe atrophy rating. Despite these recommendations, and the ease with which rating scales can be applied, there is still relatively low uptake in routine clinical assessments. Careful consideration of atrophy rating scales is needed to verify their diagnostic potential and encourage uptake among clinicians. Determining the added value of combining scores from visual rating in different brain regions may also increase the diagnostic value of these tools. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Abnormal right hepatic artery injury resulting in right hepatic atrophy: diagnosed by laparoscopic cholecystectomy

    PubMed Central

    Martino, Valter; Ferrarese, Alessia; Bindi, Marco; Marola, Silvia; Gentile, Valentina; Rivelli, Matteo; Ferrara, Yuri; Enrico, Stefano; Berti, Stefano; Solej, Mario

    2015-01-01

    An intact hepatic artery is the gateway to successful hepato-biliary surgery. Introduction of laproscopic cholecystectomy (LC) has stimulated a renewed interest in the anatomy of hepatic artery. In this case report we have highlighted importance of variations of right hepatic artery in terms of origin and course We present a rare asymptomatic case of liver atrophy due to an intraoperative lesion of right hepatic artery. We also performed a literature review about surgical vascular lesions and tried to confirm the right concept behind “non trivial procedure” of the LC. PMID:28352750

  7. Mutations in COQ2 in familial and sporadic multiple-system atrophy.

    PubMed

    2013-07-18

    Multiple-system atrophy is an intractable neurodegenerative disease characterized by autonomic failure in addition to various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. Although multiple-system atrophy is widely considered to be a nongenetic disorder, we previously identified multiplex families with this disease, which indicates the involvement of genetic components. In combination with linkage analysis, we performed whole-genome sequencing of a sample obtained from a member of a multiplex family in whom multiple-system atrophy had been diagnosed on autopsy. We also performed mutational analysis of samples from members of five other multiplex families and from a Japanese series (363 patients and two sets of controls, one of 520 persons and one of 2383 persons), a European series (223 patients and 315 controls), and a North American series (172 patients and 294 controls). On the basis of these analyses, we used a yeast complementation assay and measured enzyme activity of parahydroxybenzoate-polyprenyl transferase. This enzyme is encoded by the gene COQ2 and is essential for the biosynthesis of coenzyme Q10. Levels of coenzyme Q10 in lymphoblastoid cells and brain tissue were measured on high-performance liquid chromatography. We identified a homozygous mutation (M78V-V343A/M78V-V343A) and compound heterozygous mutations (R337X/V343A) in COQ2 in two multiplex families. Furthermore, we found that a common variant (V343A) and multiple rare variants in COQ2, all of which are functionally impaired, are associated with sporadic multiple-system atrophy. The V343A variant was exclusively observed in the Japanese population. Functionally impaired variants of COQ2 were associated with an increased risk of multiple-system atrophy in multiplex families and patients with sporadic disease, providing evidence of a role of impaired COQ2 activities in the pathogenesis of this disease. (Funded by the Japan Society for the Promotion of Science and

  8. Progression of subcortical atrophy and iron deposition in multiple system atrophy: a comparison between clinical subtypes.

    PubMed

    Lee, Jae-Hyeok; Kim, Tae-Hyung; Mun, Chi-Woong; Kim, Tae-Hyoung; Han, Yong-Hee

    2015-08-01

    Magnetic resonance imaging (MRI) can be useful not only for the diagnosis of multiple system atrophy (MSA) itself, but also to distinguish between different clinical subtypes. This study aimed to investigate whether there are differences in the progression of subcortical atrophy and iron deposition between two variants of MSA. Two serial MRIs at baseline and follow-up were analyzed in eight patients with the parkinsonian variant MSA (MSA-P), nine patients with cerebellar variant MSA (MSA-C), and fifteen patients with Parkinson's disease (PD). The R2* values and volumes were calculated for the selected subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) using an automated region-based analysis. In both volume and R2*, a higher rate of progression was identified in MSA-P patients. Volumetric analysis showed significantly more rapid progression of putamen and caudate nucleus in MSA-P than in MSA-C. With regard to R2* changes, a significant increase at follow-up and a higher rate of progression were identified in the putamen of MSA-P group compared to MSA-C and PD groups. This longitudinal study revealed different progression rates of MRI markers between MSA-P and MSA-C. Iron-related degeneration in the putamen may be more specific for MSA-P.

  9. Acoustic Characteristics of Stridor in Multiple System Atrophy

    PubMed Central

    Lee, Jee Young; Joo, Eun Yeon; Nam, Hyunwoo

    2016-01-01

    Nocturnal stridor is a breathing disorder prevalent in patients with multiple system atrophy (MSA). An improved understanding of this breathing disorder is essential since nocturnal stridor carries a poor prognosis (an increased risk of sudden death). In this study, we aimed to classify types of stridor by sound analysis and to reveal their clinical significance. Patients who met the criteria for probable MSA and had undergone polysomnography (PSG) were recruited. Patients were then assessed clinically with sleep questionnaires, including the Pittsburgh Sleep Quality Index, and the Hoehn and Yahr scale. Nocturnal stridor and snoring were analyzed with the Multi-Dimensional Voice Program. Nocturnal stridor was recorded in 22 patients and snoring in 18 patients using the PSG. Waveforms of stridors were classified into rhythmic or semirhythmic after analysis of the oscillogram. Formants and harmonics were observed in both types of stridor, but not in snoring. Of the 22 patients diagnosed with stridor during the present study, fifteen have subsequently died, with the time to death after the PSG study being 1.9 ± 1.4 years (range 0.8 to 5.0 years). The rhythmic waveform group presented higher scores on the Hoehn and Yahr scale and the survival outcome of this group was lower compared to the semirhythmic waveform group (p = 0.030, p = 0.014). In the Kaplan Meier’s survival curve, the outcome of patients with rhythmic waveform was significantly less favorable than the outcome of patients with semirhythmic waveform (log-rank test, p < 0.001). Stridor in MSA can be classified into rhythmic and semirhythmic types and the rhythmic component signifies a poorer outcome. PMID:27093692

  10. A Case of Multiple System Atrophy-Cerebellar Type Preceded by Dementia

    PubMed Central

    Jang, Eun Hye; Lee, Joo Kyung; Jang, Hyun Jung; Kim, Mi-Jung; Chung, Sun Ju

    2012-01-01

    Multiple system atrophy (MSA) is a sporadic, adult-onset disease characterized by progressive degeneration of nervous systems including cerebellar, pyramidal, extrapyramidal, and autonomic system. Although a few recent studies reported that cognitive impairments could occur in patients with MSA, prominent dementia with progressive decline is not a typical clinical manifestation of MSA. In particular, dementia with MSA-cerebellar type is very rare. We have experienced a patient with 2-year history of severe cognitive impairment, who was finally diagnosed as MSA-cerebellar type. PMID:24868414

  11. Expanding the spectrum of neuronal pathology in multiple system atrophy.

    PubMed

    Cykowski, Matthew D; Coon, Elizabeth A; Powell, Suzanne Z; Jenkins, Sarah M; Benarroch, Eduardo E; Low, Phillip A; Schmeichel, Ann M; Parisi, Joseph E

    2015-08-01

    Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients

  12. Expanding the spectrum of neuronal pathology in multiple system atrophy

    PubMed Central

    Cykowski, Matthew D.; Coon, Elizabeth A.; Powell, Suzanne Z.; Jenkins, Sarah M.; Benarroch, Eduardo E.; Low, Phillip A.; Schmeichel, Ann M.

    2015-01-01

    Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients

  13. Multiple system atrophy (MSA) with massive macrophage infiltration in the ponto-cerebellar afferent system.

    PubMed

    Yokoyama, Teruo; Hasegawa, Kazuko; Horiuchi, Emiko; Yagishita, Saburou

    2007-08-01

    Multiple system atrophy (MSA) is characterized pathologically by a systemic degeneration of the olivopontocerebellar (OPC), striatonigral (SN) and autonomic systems. Massive glial cytoplasmic inclusions (GCIs) are specific for this disease. Massive lipid-laden macrophage infiltration in the degenerating tracts has not been described up to now. We here report a case of MSA with this rare event in the ponto-cerebellar (cerebellopetal) fibers. The patient, 54-year-old housewife, developed ataxia. At the age of 55 years, she was diagnosed as having MSA by cerebellar ataxia, extrapyramidal signs, autonomic failure and Horner syndrome. She died from asphyxia at the age of 57. The autopsy revealed OPC and SN system atrophy, degeneration and numerous GCIs, compatible with MSA. Numerous lipid-laden macrophages were seen in the pontine nuclei and its transverse fibers including the white matter of the cerebellum, which has not been reported up to now. There was no macrophage infiltration in the other areas. Transient ischemia, infarction and wallerian degeneration do not account for this rare event. The ponto-cerebellar (cerebellopetal) tract pathology, as observed by postmortem neuropathological study, may occur in the context of MSA.

  14. Can patients without early, prominent visual deficits still be diagnosed of posterior cortical atrophy?

    PubMed Central

    Suárez-González, A.; Crutch, S.J.; Roldán Lora, F.; Franco-Macías, E.; Gil-Néciga, E.

    2016-01-01

    Background Early and progressive disabling visual impairment is a core feature for the diagnosis of posterior cortical atrophy (PCA). However, some individuals that fulfil criteria over time might initially present with an onset of prominent posterior dysfunction other than visuoperceptual. Methods The clinical profile of five patients with a predominantly ‘non-visual’ posterior presentation (PCA2) was investigated and compared with sixteen individuals with visually predominant PCA (PCA1) and eighteen with typical amnestic Alzheimer disease (tAD). Results PCA2 patients showed significantly better performance than PCA1 in one visuospatial task and were free of Balint's syndrome and visual agnosia. Compared to tAD, PCA2 showed trends towards significantly lower performance in visuoperceptual tasks, more severe apraxia and more symptoms of Gerstmann's syndrome. Conclusions Our sample of PCA2 patients did not present with clinically prominent visual symptoms but did show visual dysfunction on formal neuropsychological assessment (less pronounced than in PCA1 but more than in tAD) in addition to other posterior deficits. Broadening the definition of PCA to encompass individuals presenting with prominent ‘non-visual’ posterior dysfunction should be potentially considered in clinical and research contexts. PMID:27423559

  15. Whole-Brain Atrophy Rate in Idiopathic Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy

    PubMed Central

    Guevara, C.; Bulatova, K.; Barker, G. J.; Gonzalez, G.; Crossley, N.; Kempton, M. J.

    2016-01-01

    In multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the absence of surrogate endpoints makes clinical trials long and expensive. We aim to determine annualized whole-brain atrophy rates (a-WBAR) in idiopathic Parkinson's disease (IPD), MSA, and PSP. Ten healthy controls, 20 IPD, 12 PSP, and 8 MSA patients were studied using a volumetric MRI technique (SIENA). In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17–0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32–0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.26% ± 0.51 (CI 95%: 0.95–1.58). In MSA, a-WBAR was 1.65% ± 1.12 (CI 95%: 0.71–2.59). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in the IPD group (p = 0.004 and p < 0.001, resp.). In PSP, the use of a-WBAR required one-half of the patients needed for clinical scales to detect a 50% reduction in their progression. In MSA, one-quarter of the patients would be needed to detect the same effect. a-WBAR is a reasonable candidate to consider as a surrogate endpoint in short clinical trials using smaller sample sizes. The confidence intervals for a-WBAR may add a potential retrospective application for a-WBAR to improve the diagnostic accuracy of MSA and PSP versus IPD. PMID:27190673

  16. Differentiation of Parkinsonism-Predominant Multiple System Atrophy from Idiopathic Parkinson Disease Using 3T Susceptibility-Weighted MR Imaging, Focusing on Putaminal Change and Lesion Asymmetry.

    PubMed

    Hwang, I; Sohn, C-H; Kang, K M; Jeon, B S; Kim, H-J; Choi, S H; Yun, T J; Kim, J-H

    2015-12-01

    Asymmetric presentation of clinical feature in parkinsonism is common, but correlatable radiologic feature is not clearly defined. Our aim was to evaluate 3T susceptibility-weighted imaging findings for differentiating parkinsonism-predominant multiple system atrophy from idiopathic Parkinson disease, focusing on putaminal changes and lesion asymmetry. This retrospective cohort study included 27 patients with parkinsonism-predominant multiple system atrophy and 50 patients with idiopathic Parkinson disease diagnosed clinically. Twenty-seven age-matched subjects without evidence of movement disorders who underwent SWI were included as the control group. A consensus was reached by 2 radiologists who visually assessed SWI for the presence of putaminal atrophy and marked signal hypointensity on each side of the posterolateral putamen. We also quantitatively measured putaminal width and phase-shift values. The mean disease duration was 4.7 years for the patients with parkinsonism-predominant multiple system atrophy and 7.8 years for the patients with idiopathic Parkinson disease. In the patients with parkinsonism-predominant multiple system atrophy, putaminal atrophy was frequently observed (14/27, 51.9%) and was most commonly found in the unilateral putamen (13/14). Marked signal hypointensity was observed in 12 patients with parkinsonism-predominant multiple system atrophy (44.4%). No patients with idiopathic Parkinson disease or healthy controls showed putaminal atrophy or marked signal hypointensity. Quantitatively measured putaminal width, phase-shift values, and the ratio of mean phase-shift values for the dominant and nondominant sides were significantly different between the parkinsonism-predominant multiple system atrophy group and the idiopathic Parkinson disease and healthy control groups (P < .001). 3T SWI can visualize putaminal atrophy and marked signal hypointensity in patients with parkinsonism-predominant multiple system atrophy with high specificity

  17. Counteracting Muscle Atrophy using Galvanic Stimulation of the Vestibular System

    NASA Technical Reports Server (NTRS)

    Fox, Robert A.; Polyakov, Igor

    1999-01-01

    The unloading of weight bearing from antigravity muscles during space flight produces significant muscle atrophy and is one of the most serious health problems facing the space program. Various exercise regimens have been developed and used either alone or in combination with pharmacological techniques to ameliorate this atrophy, but no effective countermeasure exists for this problem. The research in this project was conducted to evaluate the potential use of vestibular galvanic stimulation (VGS) to prevent muscle atrophy resulting from unloading of weight bearing from antigravity muscles. This approach was developed based on two concepts related to the process of maintaining the status of the anti-gravity neuromuscular system. These two premises are: (1) The "tone," or bias on spinal motorneurons is affected by vestibular projections that contribute importantly to maintaining muscle health and status. (2) VGS can be used to modify the excitability, or 'tone' of motorneuron of antigravity muscles. Thus, the strategy is to use VGS to modify the gain of vestibular projections to antigravity muscles and thereby change the general status of these muscles.

  18. Counteracting Muscle Atrophy using Galvanic Stimulation of the Vestibular System

    NASA Technical Reports Server (NTRS)

    Fox, Robert A.; Polyakov, Igor

    1999-01-01

    The unloading of weight bearing from antigravity muscles during space flight produces significant muscle atrophy and is one of the most serious health problems facing the space program. Various exercise regimens have been developed and used either alone or in combination with pharmacological techniques to ameliorate this atrophy, but no effective countermeasure exists for this problem. The research in this project was conducted to evaluate the potential use of vestibular galvanic stimulation (VGS) to prevent muscle atrophy resulting from unloading of weight bearing from antigravity muscles. This approach was developed based on two concepts related to the process of maintaining the status of the anti-gravity neuromuscular system. These two premises are: (1) The "tone," or bias on spinal motorneurons is affected by vestibular projections that contribute importantly to maintaining muscle health and status. (2) VGS can be used to modify the excitability, or 'tone' of motorneuron of antigravity muscles. Thus, the strategy is to use VGS to modify the gain of vestibular projections to antigravity muscles and thereby change the general status of these muscles.

  19. Significance and usefulness of heart rate variability in patients with multiple system atrophy.

    PubMed

    Furushima, Hiroshi; Shimohata, Takayoshi; Nakayama, Hideaki; Ozawa, Tetsutaro; Chinushi, Masaomi; Aizawa, Yoshifusa; Nishizawa, Masatoyo

    2012-04-01

    The purpose of this study was to investigate whether heart rate variability parameters can be useful for evaluating cardiac autonomic dysfunction in multiple system atrophy patients. Both the time and frequency domains of heart rate variability were investigated among 17 multiple system atrophy patients and 27 normal control subjects. All time- and frequency-domain measures, except the low- to high-frequency ratio, were significantly lower in multiple system atrophy patients than in controls. In multiple system atrophy patients, there were significant inverse correlations between heart rate variability parameters and disease duration, as well as disease severity, but heart rate variability parameters were not affected by other autonomic dysfunctions. The cardiac autonomic state of multiple system atrophy was characterized by decreases in both sympathetic and parasympathetic tones. Because heart rate variability parameters were not affected by other autonomic dysfunctions, this may be a useful method for evaluating cardiac autonomic dysfunction in multiple system atrophy. Copyright © 2012 Movement Disorder Society.

  20. Involvement of medullary serotonergic groups in multiple system atrophy.

    PubMed

    Benarroch, Eduardo E; Schmeichel, Ann M; Low, Phillip A; Parisi, Joseph E

    2004-03-01

    We sought to determine whether medullary serotonergic neurons were affected in multiple system atrophy (MSA). Immunostaining for tryptophan hydroxylase was performed on serial 50 microm sections of the medulla of brains obtained at autopsy from six control subjects, eight subjects with clinical diagnosis of MSA, and four with Parkinson's disease. There was a severe depletion of serotonergic neurons in the nucleus raphe magnus, raphe obscurus, raphe pallidus, and ventrolateral medulla in MSA. Depletion of serotonergic neurons may contribute to impaired control of sympathetic outflow and other abnormalities in MSA.

  1. Instrumentation System Diagnoses a Thermocouple

    NASA Technical Reports Server (NTRS)

    Perotti, Jose; Santiago, Josephine; Mata, Carlos; Vokrot, Peter; Zavala, Carlos; Burns, Bradley

    2008-01-01

    An improved self-validating thermocouple (SVT) instrumentation system not only acquires readings from a thermocouple but is also capable of detecting deterioration and a variety of discrete faults in the thermocouple and its lead wires. Prime examples of detectable discrete faults and deterioration include open- and short-circuit conditions and debonding of the thermocouple junction from the object, the temperature of which one seeks to measure. Debonding is the most common cause of errors in thermocouple measurements, but most prior SVT instrumentation systems have not been capable of detecting debonding. The improved SVT instrumentation system includes power circuitry, a cold-junction compensator, signal-conditioning circuitry, pulse-width-modulation (PWM) thermocouple-excitation circuitry, an analog-to-digital converter (ADC), a digital data processor, and a universal serial bus (USB) interface. The system can operate in any of the following three modes: temperature measurement, thermocouple validation, and bonding/debonding detection. The software running in the processor includes components that implement statistical algorithms to evaluate the state of the thermocouple and the instrumentation system. When the power is first turned on, the user can elect to start a diagnosis/ monitoring sequence, in which the PWM is used to estimate the characteristic times corresponding to the correct configuration. The user also has the option of using previous diagnostic values, which are stored in an electrically erasable, programmable read-only memory so that they are available every time the power is turned on.

  2. Diagnose

    NASA Astrophysics Data System (ADS)

    Schauer, Wolfgang

    Die Zunahme der Elektronik im Kraftfahrzeug, die Nutzung von Software zur Steuerung des Fahrzeugs und die erhöhte Komplexität moderner Einspritzsysteme stellen hohe Anforderungen an das Diagnosekonzept, die Überwachung im Fahrbetrieb (On-Board-Diagnose) und die Werkstattdiagnose (Bild 1). Basis der Werkstattdiagnose ist die geführte Fehlersuche, die verschiedene Möglichkeiten von Onboard- und Offboard-Prüfmethoden und Prüfgeräten verknüpft. Im Zuge der Verschärfung der Abgasgesetzgebung und der Forderung nach laufender Überwachung hat auch der Gesetzgeber die On-Board-Diagnose als Hilfsmittel zur Abgasüberwachung erkannt und eine herstellerunabhängige Standardisierung geschaffen. Dieses zusätzlich installierte System wird OBD-System (On Board Diagnostic System) genannt.

  3. Multiple system atrophy: clinicopathological characteristics in Japanese patients

    PubMed Central

    OZAWA, Tetsutaro; ONODERA, Osamu

    2017-01-01

    Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that has both clinical and pathological variants. Clinical examples include MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA-P), whereas olivopontocerebellar atrophy and striatonigral degeneration represent pathological variants. We performed systematic reviews of studies that addressed the relative frequencies of clinical or pathological variants of MSA in various populations to determine the clinicopathological characteristics in Japanese MSA. The results revealed that the majority of Japanese patients have MSA-C, while the majority of patients in Europe and North America have MSA-P. A comparative study of MSA pathology showed that the olivopontocerebellar-predominant pathology was more frequent in Japanese MSA than in British MSA. Demonstrated differences in pathological subtype thus appear consistent with differences in the clinical subtype of MSA demonstrated between Japan and European populations. We concluded that olivopontocerebellar-predominant pathology and MSA-C may represent clinicopathological characteristics in Japanese MSA. Factors determining predominant involvement of olivopontocerebellar regions in MSA should therefore be explored. PMID:28496050

  4. The nature of the autonomic dysfunction in multiple system atrophy

    NASA Technical Reports Server (NTRS)

    Parikh, Samir M.; Diedrich, Andre; Biaggioni, Italo; Robertson, David

    2002-01-01

    The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

  5. The nature of the autonomic dysfunction in multiple system atrophy

    NASA Technical Reports Server (NTRS)

    Parikh, Samir M.; Diedrich, Andre; Biaggioni, Italo; Robertson, David

    2002-01-01

    The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

  6. Systems-based discovery of tomatidine as a natural small molecule inhibitor of skeletal muscle atrophy.

    PubMed

    Dyle, Michael C; Ebert, Scott M; Cook, Daniel P; Kunkel, Steven D; Fox, Daniel K; Bongers, Kale S; Bullard, Steven A; Dierdorff, Jason M; Adams, Christopher M

    2014-05-23

    Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy.

  7. Systems-based Discovery of Tomatidine as a Natural Small Molecule Inhibitor of Skeletal Muscle Atrophy*

    PubMed Central

    Dyle, Michael C.; Ebert, Scott M.; Cook, Daniel P.; Kunkel, Steven D.; Fox, Daniel K.; Bongers, Kale S.; Bullard, Steven A.; Dierdorff, Jason M.; Adams, Christopher M.

    2014-01-01

    Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy. PMID:24719321

  8. Multiple system atrophy--the nature of the beast.

    PubMed Central

    Quinn, N

    1989-01-01

    Multiple system atrophy (MSA) is generally considered a rare disease, but may account for up to 10% of patients with Parkinsonism. The profusion of names for this disease, which may present to general physicians, psychiatrists, cardiologists, autonomic specialists, general neurologists and those with a special interest in Parkinsonism (this author's own perspective) or cerebellar disorders, together with ignorance of its protean manifestations, may account for its underrecognition and misdiagnosis. In this article, the history and nosology of the condition are considered, and provisional diagnostic criteria are advanced. The usefulness (or otherwise) of ancillary investigations is addressed, and the shortcomings of current methods of treatment are stressed. As with idiopathic Parkinson's disease, the ultimate goal of eradicating the disease entails better diagnosis in order to establish the cause, and thence to develop a radical treatment capable of preventing or arresting the disease process. PMID:2666581

  9. Multiple system atrophy: current and future approaches to management

    PubMed Central

    Flabeau, Olivier; Meissner, Wassilios G.; Tison, François

    2010-01-01

    Multiple system atrophy (MSA) is a rare neurodegenerative disorder without any effective treatment in slowing or stopping disease progression. It is characterized by poor levodopa responsive Parkinsonism, cerebellar ataxia, pyramidal signs and autonomic failure in any combination. Current therapeutic strategies are primarily based on dopamine replacement and improvement of autonomic failure. However, symptomatic management remains disappointing and no curative treatment is yet available. Recent experimental evidence has confirmed the key role of alpha-synuclein aggregation in the pathogenesis of MSA. Referring to this hypothesis, transgenic and toxic animal models have been developed to assess candidate drugs for MSA. The standardization of diagnosis criteria and assessment procedures will allow large multicentre clinical trials to be conducted. In this article we review the available symptomatic treatment, recent results of studies investigating potential neuroprotective drugs, and future approaches for the management in MSA. PMID:21179616

  10. Multiple System Atrophy: A Clinical and Neuropathological Perspective

    PubMed Central

    Ubhi, Kiren; Low, Phillip; Masliah, Eliezer

    2011-01-01

    Multiple System Atrophy (MSA) is a neurodegenerative disease presenting with motor abnormalities including akinesia, rigidity and postural instability. Whilst improved diagnostic criteria have aided accurate diagnosis of MSA, understanding of neuropathological aspects underlying MSA was bolstered by the identification of alpha-synuclein (α-syn) as the primary constituent of the abnormal protein aggregations observed in the brains of MSA patients. The generation of transgenic animal models of MSA coupled with an increasing understanding of the biochemical structure and function of α-syn has highlighted a number of key pathological pathways thought to underlie the neurodegeneration observed in MSA. This review will summarize key findings in the field, discuss current areas of debate and describe current experimental approaches towards disease-modifying therapies. PMID:21962754

  11. Pan-American Consortium of Multiple System Atrophy (PANMSA). A Pan-American multicentre cohort study of multiple system atrophy.

    PubMed

    Gatto, Emilia; Rodríguez-Violante, Mayela; Cosentino, Carlos; Chana-Cuevas, Pedro; Miranda, Marcelo; Gallin, Ellin; Etcheverry, Jose L; Nuñez, Yesenia; Parisi, Virginia; Persi, Gabriel; Vecchi, Celeste; Sanguinetti, Ana; Alleva, Alejandro; Aparcana, Juliana; Torres, Luis; Litvan, Irene

    2014-01-01

    Multiple system atrophy (MSA) is an adult-onset and rapidly progressive, neurodegenerative condition that presents with autonomic dysfunction, parkinsonism, cerebellar ataxia and corticospinal deficits. Clinical, demographic and epidemiological data from different regions have provided valuable information concerning the natural history of MSA. There are no published data of Multiple System Atrophy (MSA) in Latin American countries. To describe clinical and epidemiological data of patients with "possible" MSA from seven referral movement disorders centers from Argentina, Chile, Mexico, Peru and United States. We conducted a retrospective, observational, cross-sectional Pan-American multicentre cohort study of MSA. The sample was composed of 82 females and 77 men with the diagnosis of "possible" MSA with a mean age at onset of 65 ± 10 years. 67.29% of the individuals had a MSA-P variant with a mean age at onset of 61.47 ± 10.28 years, whereas the mean age at onset in the MSA-C patients was 57.44 ± 10.58 years. Interestingly, MSA-C-was more prevalent in Non-Caucasian (50-Mestizo and 2 Asian patients) than Caucasians (51.92% vs. 20.79%, p = 0.0001). Dysautonomic symptoms were present in 95.6% of the patients, parkinsonism in 85.5%, pyramidal signs in 25.8% and depression in 48.4% of the patients. Our epidemiological and clinical data appears to be similar to other Western international series, however, of note, the MSA-C phenotype was predominant in Non-Caucasians, more specifically the Mestizo population. This observation opens a new path to explore. Larger prospective epidemiologic studies in Latin America may provide valuable information concerning MSA in the region.

  12. Fuzzy expert system for diagnosing diabetic neuropathy.

    PubMed

    Rahmani Katigari, Meysam; Ayatollahi, Haleh; Malek, Mojtaba; Kamkar Haghighi, Mehran

    2017-02-15

    To design a fuzzy expert system to help detect and diagnose the severity of diabetic neuropathy. The research was completed in 2014 and consisted of two main phases. In the first phase, the diagnostic parameters were determined based on the literature review and by investigating specialists' perspectives (n = 8). In the second phase, 244 medical records related to the patients who were visited in an endocrinology and metabolism research centre during the first six months of 2014 and were primarily diagnosed with diabetic neuropathy, were used to test the sensitivity, specificity, and accuracy of the fuzzy expert system. The final diagnostic parameters included the duration of diabetes, the score of a symptom examination based on the Michigan questionnaire, the score of a sign examination based on the Michigan questionnaire, the glycolysis haemoglobin level, fasting blood sugar, blood creatinine, and albuminuria. The output variable was the severity of diabetic neuropathy which was shown as a number between zero and 10, had been divided into four categories: absence of the disease, (the degree of severity) mild, moderate, and severe. The interface of the system was designed by ASP.Net (Active Server Pages Network Enabled Technology) and the system function was tested in terms of sensitivity (true positive rate) (89%), specificity (true negative rate) (98%), and accuracy (a proportion of true results, both positive and negative) (93%). The system designed in this study can help specialists and general practitioners to diagnose the disease more quickly to improve the quality of care for patients.

  13. Clinicopathological study of 35 cases of multiple system atrophy.

    PubMed Central

    Wenning, G K; Ben-Shlomo, Y; Magalhães, M; Daniel, S E; Quinn, N P

    1995-01-01

    The clinical and pathological features of 35 cases with multiple system atrophy collected in the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) between 1985 and 1992 have been analysed. The median age of onset was 55 (range 33.3-75.8) years and median survival was 7.3 (range 2.1-11.5) years. Parkinsonism, usually asymmetric, occurred in all, and autonomic failure in all but one case. Cerebellar signs were noted in 34% and pyramidal features in 54% of the cases. Glial cytoplasmic inclusions were found in all cases with adequate fixation. Lewy bodies were detected in three cases. The substantia nigra was (usually severely) depleted of cells in all cases. With two exceptions the putamen was atrophic; the caudate and pallidum were less commonly and less severely affected. Overall nigrostriatal cell loss correlated with severity of disease at the time of death. The latest, but not the best, recorded levodopa response tended to be inversely related to the degree of putaminal degeneration. The olivopontocerebellar system was involved in 88% of the cases, the cerebellar vermis usually being more severely affected than the hemispheres. The presence of associated cerebellar pathology was, however, unrelated to the presence of cerebellar signs in life. PMID:7876845

  14. Olivopontocerebellar Atrophy

    MedlinePlus

    ... and inferior olives. OPCA is present in several neurodegenerative syndromes, including inherited and non-inherited forms of ataxia (such as the hereditary spinocerebellar ataxia known as Machado-Joseph disease) and multiple system atrophy (MSA), with which it ...

  15. Convenient diagnosis of spinal and bulbar muscular atrophy using a microchip electrophoresis system.

    PubMed

    Maruyama, Hirofumi; Morino, Hiroyuki; Izumi, Yuishin; Noda, Kouichi; Kawakami, Hideshi

    2013-01-01

    Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive motor neuron disease. Lower and primary sensory neuronopathy is one of the major neuropathological changes that occurs in SBMA. However, many sings are common to SBMA and amyotrophic lateral sclerosis (ALS), and SBMA patients are sometimes diagnosed with ALS. Leuprorelin may be used to treat SBMA, but an accurate diagnosis is necessary for treatment and care. Genetic diagnosis can be performed to detect the expansion of a CAG repeat in the androgen receptor gene in SBMA patients. To screen for this expansion, we used a microchip electrophoresis system. The discrepancy between the actual repeat length and that found by the microchip electrophoresis system was roughly dependent on the repeat length. The mean difference was -6.8 base pairs (bp) in SBMA patients, -0.30 bp in controls. The microchip electrophoresis results were approximately 2 CAG repeats shorter than the actual repeat length in SBMA patients. Using this method, we screened our ALS samples (31 were familial, 271 were sporadic): 4 subjects were diagnosed with SBMA; 2 had familial ALS, and 2 had sporadic ALS (0.7%). The microchip electrophoresis system is semi-quantitative, convenient and useful for screening a large number of samples.

  16. Diagnosing Parkinson's Diseases Using Fuzzy Neural System

    PubMed Central

    Abiyev, Rahib H.; Abizade, Sanan

    2016-01-01

    This study presents the design of the recognition system that will discriminate between healthy people and people with Parkinson's disease. A diagnosing of Parkinson's diseases is performed using fusion of the fuzzy system and neural networks. The structure and learning algorithms of the proposed fuzzy neural system (FNS) are presented. The approach described in this paper allows enhancing the capability of the designed system and efficiently distinguishing healthy individuals. It was proved through simulation of the system that has been performed using data obtained from UCI machine learning repository. A comparative study was carried out and the simulation results demonstrated that the proposed fuzzy neural system improves the recognition rate of the designed system. PMID:26881009

  17. A genome-wide association study in multiple system atrophy

    PubMed Central

    Sailer, Anna; Nalls, Michael A.; Schulte, Claudia; Federoff, Monica; Price, T. Ryan; Lees, Andrew; Ross, Owen A.; Dickson, Dennis W.; Mok, Kin; Mencacci, Niccolo E.; Schottlaender, Lucia; Chelban, Viorica; Ling, Helen; O'Sullivan, Sean S.; Wood, Nicholas W.; Traynor, Bryan J.; Ferrucci, Luigi; Federoff, Howard J.; Mhyre, Timothy R.; Morris, Huw R.; Deuschl, Günther; Quinn, Niall; Widner, Hakan; Albanese, Alberto; Infante, Jon; Bhatia, Kailash P.; Poewe, Werner; Oertel, Wolfgang; Höglinger, Günter U.; Wüllner, Ullrich; Goldwurm, Stefano; Pellecchia, Maria Teresa; Ferreira, Joaquim; Tolosa, Eduardo; Bloem, Bastiaan R.; Rascol, Olivier; Meissner, Wassilios G.; Hardy, John A.; Revesz, Tamas; Holton, Janice L.; Gasser, Thomas; Wenning, Gregor K.; Singleton, Andrew B.

    2016-01-01

    Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). Methods: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. Results: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10−6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. Conclusions: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps. PMID:27629089

  18. Animal modeling an oligodendrogliopathy--multiple system atrophy.

    PubMed

    Bleasel, Jonathan M; Halliday, Glenda M; Kim, Woojin Scott

    2016-02-09

    Multiple system atrophy (MSA) is a rare, yet rapidly-progressive neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. The definitive neuropathology differentiating MSA from Lewy body diseases is the presence of α-synuclein aggregates in oligodendrocytes (called glial cytoplasmic inclusion or GCI) rather than the fibrillar aggregates in neurons (called Lewy bodies). This makes the pathological pathway(s) in MSA unique in that oligodendrocytes are involved rather than predominantly neurons, as is most other neurodegenerative disorders. MSA is therefore regarded as an oligodendrogliopathy. The etiology of MSA is unknown. No definitive risk factors have been identified, although α-synuclein and other genes have been variably linked to MSA risk. Utilization of postmortem brain tissues has greatly advanced our understanding of GCI pathology and the subsequent neurodegeneration. However, extrapolating the early pathogenesis of MSA from such resource has been difficult and limiting. In recent years, cell and animal models developed for MSA have been instrumental in delineating unique MSA pathological pathways, as well as aiding in clinical phenotyping. The purpose of this review is to bring together and discuss various animal models that have been developed for MSA and how they have advanced our understanding of MSA pathogenesis, particularly the dynamics of α-synuclein aggregation. This review will also discuss how animal models have been used to explore potential therapeutic avenues for MSA, and future directions of MSA modeling.

  19. Chronic Traumatic Encephalopathy Pathology in Multiple System Atrophy

    PubMed Central

    Koga, Shunsuke; Dickson, Dennis W.

    2016-01-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder associated with repetitive traumatic brain injury. Multiple system atrophy (MSA) is a Parkinsonian disorder that can result in repetitive falls with associated head trauma. We hypothesized that patients with neurodegenerative disorders like MSA could develop CTE pathology. Therefore, we assessed CTE pathology in 139 MSA cases in our brain bank. Sections from convexity cerebral cortices were screened by immunohistochemistry with anti-phospho-tau antibody. For cases with suggestive CTE pathology, further sections of basal forebrain and hippocampus were immunostained. Consensus criteria were used to make the diagnosis of CTE and aging-related tau astrogliopathy (ARTAG) was differentiated from CTE pathology. Pertinent clinical information was derived from the available records and online searches. Of the 139 MSA cases, 8 (6%) had CTE pathology and 10 (8%) had ARTAG pathology. All 8 cases with CTE were male and 4 of them had a documented history of contact sports. The median age at death in MSA with CTE was younger than in MSA without CTE or MSA with ARTAG (60, 67, and 74 years, respectively; p = 0.002). Even without a known history of contact sports or head trauma, a small subset of cases with MSA had CTE pathology. PMID:27543120

  20. Urinary and erectile dysfunction in multiple system atrophy (MSA).

    PubMed

    Papatsoris, A G; Papapetropoulos, S; Singer, C; Deliveliotis, C

    2008-01-01

    Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined etiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar, and pyramidal signs. Despite the lack of effective therapies, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Urinary and erectile dysfunction (ED) symptoms are prominent early features in male MSA patients. Lower urinary tract infections (UTIs) are a major cause of morbidity and mortality in this disorder. More than 50% of MSA patients suffer from recurrent lower UTIs and a significant number (approximately 25%) die of complications related to them. Urogenital symptoms in MSA are usually due to a complex mixture of central and peripheral nervous abnormalities, sometimes superimposed on previous local pathological conditions such as benign prostatic hyperplasia and perineal laxity. There have been instances were MSA-related urological symptoms were confused with symptoms of benign prostatic hyperplasia, leading to unnecessary urological surgery. In this review, we present the phenotypic range and therapeutic approaches for common storage and voiding urological symptoms and ED, in patients with MSA.

  1. Therapeutic advances in multiple system atrophy and progressive supranuclear palsy.

    PubMed

    Poewe, Werner; Mahlknecht, Philipp; Krismer, Florian

    2015-09-15

    Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these diseases and in the search for biomarkers have paved the way for the first large and well-designed clinical trials aiming at disease modification. Targets of intervention in these trials have included α-synuclein inclusion pathology in the case of MSA and tau-related mechanisms in PSP. Since 2013, four large randomized, placebo-controlled, double-blind disease-modification trials have been completed and published, using rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), or davunetide (PSP). All of these failed to demonstrate signal efficacy with regard to the primary outcome measures. In addition, two randomized, placebo-controlled, double-blind trials have studied the efficacy of droxidopa in the symptomatic treatment of neurogenic orthostatic hypotension, including patients with MSA, with positive results in one trial. This review summarizes the design and the outcomes of these and other smaller trials published since 2013 and attempts to highlight priority areas of future therapeutic research in MSA and PSP. © 2015 International Parkinson and Movement Disorder Society.

  2. Diffusion tensor imaging in the characterization of multiple system atrophy

    PubMed Central

    Rulseh, Aaron Michael; Keller, Jiri; Rusz, Jan; Syka, Michael; Brozova, Hana; Rusina, Robert; Havrankova, Petra; Zarubova, Katerina; Malikova, Hana; Jech, Robert; Vymazal, Josef

    2016-01-01

    Purpose Multiple system atrophy (MSA) is a rare neurodegenerative disease that remains poorly understood, and the diagnosis of MSA continues to be challenging. We endeavored to improve the diagnostic process and understanding of in vivo characteristics of MSA by diffusion tensor imaging (DTI). Materials and methods Twenty MSA subjects, ten parkinsonian dominant (MSA-P), ten cerebellar dominant (MSA-C), and 20 healthy volunteer subjects were recruited. Fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity maps were processed using tract-based spatial statistics. Diffusion data were additionally evaluated in the basal ganglia. A support vector machine was used to assess diagnostic utility, leave-one-out cross-validation in the evaluation of classification schemes, and receiver operating characteristic analyses to determine cutoff values. Results We detected widespread changes in the brain white matter of MSA subjects; however, no group-wise differences were found between MSA-C and MSA-P subgroups. Altered DTI metrics in the putamen and middle cerebellar peduncles were associated with a positive parkinsonian and cerebellar phenotype, respectively. Concerning clinical applicability, we achieved high classification performance on mean diffusivity data in the combined bilateral putamen and middle cerebellar peduncle (accuracy 90.3%±9%, sensitivity 86.5%±11%, and specificity 99.3%±4%). Conclusion DTI in the middle cerebellar peduncle and putamen may be used in the diagnosis of MSA with a high degree of accuracy. PMID:27616888

  3. Transmission of multiple system atrophy prions to transgenic mice

    PubMed Central

    Watts, Joel C.; Giles, Kurt; Oehler, Abby; Middleton, Lefkos; Dexter, David T.; Gentleman, Steve M.; DeArmond, Stephen J.; Prusiner, Stanley B.

    2013-01-01

    Prions are proteins that adopt alternative conformations, which become self-propagating. Increasing evidence argues that prions feature in the synucleinopathies that include Parkinson’s disease, Lewy body dementia, and multiple system atrophy (MSA). Although TgM83+/+ mice homozygous for a mutant A53T α-synuclein transgene begin developing CNS dysfunction spontaneously at ∼10 mo of age, uninoculated TgM83+/− mice (hemizygous for the transgene) remain healthy. To determine whether MSA brains contain α-synuclein prions, we inoculated the TgM83+/− mice with brain homogenates from two pathologically confirmed MSA cases. Inoculated TgM83+/− mice developed progressive signs of neurologic disease with an incubation period of ∼100 d, whereas the same mice inoculated with brain homogenates from spontaneously ill TgM83+/+ mice developed neurologic dysfunction in ∼210 d. Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and microglial activation as well as widespread deposits of phosphorylated α-synuclein that were proteinase K sensitive, detergent insoluble, and formic acid extractable. Our results provide compelling evidence that α-synuclein aggregates formed in the brains of MSA patients are transmissible and, as such, are prions. The MSA prion represents a unique human pathogen that is lethal upon transmission to Tg mice and as such, is reminiscent of the prion causing kuru, which was transmitted to chimpanzees nearly 5 decades ago. PMID:24218576

  4. Pathogenesis of laryngeal narrowing in patients with multiple system atrophy

    PubMed Central

    Isono, Shiroh; Shiba, Keisuke; Yamaguchi, Mika; Tanaka, Atsuko; Hattori, Takamichi; Konno, Akiyoshi; Nishino, Takashi

    2001-01-01

    We do not fully understand the pathogenesis of nocturnal laryngeal stridor in patients with multiple system atrophy (MSA). Recent studies suggest that inspiratory thyroarytenoid (TA) muscle activation has a role in the development of the stridor.The breathing pattern and firing timing of TA muscle activation were determined in ten MSA patients, anaesthetized with propofol and breathing through the laryngeal mask airway, while the behaviour of the laryngeal aperture was being observed endoscopically.Two distinct breathing patterns, i.e. no inspiratory flow limitation (no-IFL) and IFL, were identified during the measurements. During IFL, significant laryngeal narrowing was observed leading to an increase in laryngeal resistance and end-tidal carbon dioxide concentration. Development of IFL was significantly associated with the presence of phasic inspiratory activation of TA muscle. Application of continuous positive airway pressure suppressed the TA muscle activation.The results indicate that contraction of laryngeal adductors during inspiration narrows the larynx leading to development of inspiratory flow limitation accompanied by stridor in patients with MSA under general anaesthesia. PMID:11579172

  5. Analysis of the prion protein gene in multiple system atrophy.

    PubMed

    Chelban, Viorica; Manole, Andreea; Pihlstrøm, Lasse; Schottlaender, Lucia; Efthymiou, Stephanie; OConnor, Emer; Meissner, Wassilios G; Holton, Janice L; Houlden, Henry

    2017-01-01

    Neurodegenerative diseases are a very diverse group of disorders but they share some common mechanisms such as abnormally misfolded proteins with prion-like propagation and aggregation. Creutzfeldt-Jakob disease (CJD) is the most prevalent prion disease in humans. In the sporadic form of CJD the only known risk factor is the codon 129 polymorphism. Recent reports suggested that α-synuclein in multiple system atrophy (MSA) has similar pathogenic mechanisms as the prion protein. Here we present 1 Italian family with MSA and prion disease. Also, cases of concurrent MSA and prion pathology in the same individual or family suggest the possibility of molecular interaction between prion protein and α-synuclein in the process of protein accumulation and neurodegeneration, warranting further investigations. We assessed the PRNP gene by whole-exome sequencing in 264 pathologically confirmed MSA cases and 462 healthy controls to determine whether the 2 diseases share similar risk factors. We then analyzed codon 129 polymorphism by Sanger sequencing and compared with previously published results in sporadic CJD. Homozygosity at codon 129 was present in 50% of pathologically confirmed MSA cases and in 58% of normal controls (odds ratio, 0.7 (95% confidence interval of 0.5-0.9)) compared with 88.2% in sporadic CJD. Our data show that the homozygous state of position 129 in the PRNP is not a risk factor for MSA. No other variants in the PRNP gene were associated with increased risk for MSA.

  6. Skin vasodilator response to local heating in multiple system atrophy.

    PubMed

    Yamanaka, Yoshitaka; Asahina, Masato; Mathias, Christopher J; Akaogi, Yuichi; Koyama, Yu; Hattori, Takamichi

    2007-12-01

    Local heating of nonglabrous skin increases skin blood flow (SkBF) in two phases. The initial peak (P1) is mediated by a sensory-axon reflex and the plateau phase (P2) by local production of substances such as nitric oxide. We evaluated the SkBF response to local heating in 15 multiple system atrophy (MSA) patients with autonomic failure and 12 age-matched healthy controls. The mean ratio of SkBF at P1 to that at baseline (SkBF(P1)/SkBF(base) ratio) in MSA was significantly lower than that in controls (P < 0.01). The mean ratio of SkBF at P2 seemed to be slightly reduced in the MSA patients, compared with controls, although there was no significant difference. The P1 phase is thought to be mediated by a sensory-axon reflex modulated by sympathetic nerve activity. These findings are indicative of the skin sympathetic vasomotor dysfunction in MSA.

  7. Management of multiple system atrophy: state of the art.

    PubMed

    Colosimo, C; Tiple, D; Wenning, G K

    2005-12-01

    Multiple system atrophy (MSA) is a sporadic neurodegenerative disease of undetermined aetiology presenting with parkinsonian, autonomic, cerebellar, and pyramidal signs. Despite the lack of any effective therapy to reverse MSA, some of the symptoms may be improved with adequate symptomatic therapies. Medical treatment is largely aimed at mitigating the parkinsonian and autonomic features. The therapeutic results of levodopa therapy in cases of MSA are difficult to interpret because of their variability. Nevertheless, the simple statement that patients with MSA do not respond to levodopa is false. Clinical and pathologically proven series document levodopa efficacy in about 40-60% of patients with MSA and predominant parkinsonian features. Other antiparkinsonian compounds (dopamine agonists, amantadine) may also be employed, but they are not more effective than levodopa. Orthostatic hypotension (OH) can be suspected from the patient s history and subsequently documented in the clinic by measuring lying and standing blood pressure. The diagnosis ideally should be confirmed with additional laboratory tests to determine the cause and evaluate the functional deficit, so as to aid treatment. A number of pharmacological agents with different mechanisms of action have been used in MSA to reduce OH when this is symptomatic. OH can also be alleviated by avoiding aggravating factors, such as the effects of food, micturition, exposure to a warm environment, and physiological diurnal changes, and by using other non-pharmacological strategies. The treatment of the very common genitourinary symptoms (incontinence, retention, impotence) should also be considered in order to improve the quality of life of these patients.

  8. Chronic Traumatic Encephalopathy Pathology in Multiple System Atrophy.

    PubMed

    Koga, Shunsuke; Dickson, Dennis W; Bieniek, Kevin F

    2016-10-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder associated with repetitive traumatic brain injury. Multiple system atrophy (MSA) is a Parkinsonian disorder that can result in repetitive falls with associated head trauma. We hypothesized that patients with neurodegenerative disorders like MSA could develop CTE pathology. Therefore, we assessed CTE pathology in 139 MSA cases in our brain bank. Sections from convexity cerebral cortices were screened by immunohistochemistry with anti-phospho-tau antibody. For cases with suggestive CTE pathology, further sections of basal forebrain and hippocampus were immunostained. Consensus criteria were used to make the diagnosis of CTE and aging-related tau astrogliopathy (ARTAG) was differentiated from CTE pathology. Pertinent clinical information was derived from the available records and online searches. Of the 139 MSA cases, 8 (6%) had CTE pathology and 10 (8%) had ARTAG pathology. All 8 cases with CTE were male and 4 of them had a documented history of contact sports. The median age at death in MSA with CTE was younger than in MSA without CTE or MSA with ARTAG (60, 67, and 74 years, respectively; p = 0.002). Even without a known history of contact sports or head trauma, a small subset of cases with MSA had CTE pathology.

  9. Fuzzy expert system for diagnosing diabetic neuropathy

    PubMed Central

    Rahmani Katigari, Meysam; Ayatollahi, Haleh; Malek, Mojtaba; Kamkar Haghighi, Mehran

    2017-01-01

    AIM To design a fuzzy expert system to help detect and diagnose the severity of diabetic neuropathy. METHODS The research was completed in 2014 and consisted of two main phases. In the first phase, the diagnostic parameters were determined based on the literature review and by investigating specialists’ perspectives (n = 8). In the second phase, 244 medical records related to the patients who were visited in an endocrinology and metabolism research centre during the first six months of 2014 and were primarily diagnosed with diabetic neuropathy, were used to test the sensitivity, specificity, and accuracy of the fuzzy expert system. RESULTS The final diagnostic parameters included the duration of diabetes, the score of a symptom examination based on the Michigan questionnaire, the score of a sign examination based on the Michigan questionnaire, the glycolysis haemoglobin level, fasting blood sugar, blood creatinine, and albuminuria. The output variable was the severity of diabetic neuropathy which was shown as a number between zero and 10, had been divided into four categories: absence of the disease, (the degree of severity) mild, moderate, and severe. The interface of the system was designed by ASP.Net (Active Server Pages Network Enabled Technology) and the system function was tested in terms of sensitivity (true positive rate) (89%), specificity (true negative rate) (98%), and accuracy (a proportion of true results, both positive and negative) (93%). CONCLUSION The system designed in this study can help specialists and general practitioners to diagnose the disease more quickly to improve the quality of care for patients. PMID:28265346

  10. Microglial activation in multiple system atrophy: a potential role for NF-kappaB/rel proteins.

    PubMed

    Schwarz, S C; Seufferlein, T; Liptay, S; Schmid, R M; Kasischke, K; Foster, O J; Daniel, S; Schwarz, J

    1998-09-14

    Microglial activation is a prominent feature of affected brain areas in multiple system atrophy. Microglia express proinflammatory peptides, which may be a result of activation of nuclear factor-KB. We investigated the nuclear presence of RelA, the 65 kDa subunit of the NF-KB/RelA family in striatum and brain stem of patients with multiple system atrophy. Affected brain areas of patients with multiple system atrophy showed a marked immunoreactivity for nuclear Rel A p65, which was almost exclusively localized in activated microglia. Interestingly nuclear translocation of Rel A was not detected in striatal tissue of controls and Parkinson disease patients. Thus, NF-kappaB/Rel A complexes may play a role in mediating microglial activation in multiple system atrophy.

  11. Treatment of multiple system atrophy using intravenous immunoglobulin.

    PubMed

    Novak, Peter; Williams, Arlene; Ravin, Paula; Zurkiya, Omar; Abduljalil, Amir; Novak, Vera

    2012-11-01

    Multiple system atrophy (MSA) is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG) in MSA. This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS) was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment. Nine subjects were enrolled, and seven (2 women and 5 men, age range 55-64 years) completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p<0.05). Two participants dropped out from the study because of a non-threatening skin rash. The UMSARS-I (activities of daily living) and USMARS-II (motor functions) improved significantly post-treatment. UMSARS-I improved in all subjects (pre-treatment 23.9 ± 6.0 vs. post-treatment 19.0±5.9 (p=0.01). UMSARS-II improved in 5 subjects, was unchanged in 1 and worsened in 1 (pre-treatment 26.1±7.5 vs. post-treatment 23.3±7.3 (p=0.025). The MR imaging results were not different comparing pre- to post-treatment. Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed.

  12. Variants associated with Gaucher disease in multiple system atrophy

    PubMed Central

    Mitsui, Jun; Matsukawa, Takashi; Sasaki, Hidenao; Yabe, Ichiro; Matsushima, Masaaki; Dürr, Alexandra; Brice, Alexis; Takashima, Hiroshi; Kikuchi, Akio; Aoki, Masashi; Ishiura, Hiroyuki; Yasuda, Tsutomu; Date, Hidetoshi; Ahsan, Budrul; Iwata, Atsushi; Goto, Jun; Ichikawa, Yaeko; Nakahara, Yasuo; Momose, Yoshio; Takahashi, Yuji; Hara, Kenju; Kakita, Akiyoshi; Yamada, Mitsunori; Takahashi, Hitoshi; Onodera, Osamu; Nishizawa, Masatoyo; Watanabe, Hirohisa; Ito, Mizuki; Sobue, Gen; Ishikawa, Kinya; Mizusawa, Hidehiro; Kanai, Kazuaki; Hattori, Takamichi; Kuwabara, Satoshi; Arai, Kimihito; Koyano, Shigeru; Kuroiwa, Yoshiyuki; Hasegawa, Kazuko; Yuasa, Tatsuhiko; Yasui, Kenichi; Nakashima, Kenji; Ito, Hijiri; Izumi, Yuishin; Kaji, Ryuji; Kato, Takeo; Kusunoki, Susumu; Osaki, Yasushi; Horiuchi, Masahiro; Kondo, Tomoyoshi; Murayama, Shigeo; Hattori, Nobutaka; Yamamoto, Mitsutoshi; Murata, Miho; Satake, Wataru; Toda, Tatsushi; Filla, Alessandro; Klockgether, Thomas; Wüllner, Ullrich; Nicholson, Garth; Gilman, Sid; Tanner, Caroline M; Kukull, Walter A; Stern, Mathew B; Lee, Virginia M-Y; Trojanowski, John Q; Masliah, Eliezer; Low, Phillip A; Sandroni, Paola; Ozelius, Laurie J; Foroud, Tatiana; Tsuji, Shoji

    2015-01-01

    Objective Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case–control series. Methods We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants. Results In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel–Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14–5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15–5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10−3). Interpretation The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA. PMID:25909086

  13. Comparison of Different Symptom Assessment Scales for Multiple System Atrophy.

    PubMed

    Matsushima, Masaaki; Yabe, Ichiro; Oba, Koji; Sakushima, Ken; Mito, Yasunori; Takei, Asako; Houzen, Hideki; Tsuzaka, Kazufumi; Yoshida, Kazuto; Maruo, Yasunori; Sasaki, Hidenao

    2016-04-01

    To identify the most sensitive scale for use in clinical trials on multiple system atrophy (MSA), a short and sensitive scale is needed for MSA clinical trials. Potential candidates are the Unified MSA Rating Scale (UMSARS), Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), MSA Health-Related Quality of Life scale (MSA-QoL), and Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT). We enrolled patients with MSA from eight hospitals in Hokkaido, Japan. Board-certified neurologists assessed each patient at 6-month intervals and scored them on the UMSARS, SARA, BBS, MSA-QoL, and SCOPA-AUT. Score changes were evaluated using the standardized response mean (SRM). The correlation between disease duration and each score was examined. The first evaluation was conducted on 85 patients (60 patients with MSA cerebellar ataxia dominant subtype [MSA-C] and 25 patients with MSA Parkinsonism-dominant subtype [MSA-P]). Sixty-nine patients were examined after 6 months and 63 patients after 12 months. The UMSARS Part 4 had the largest SRM after 6 months and the SARA after 12 months. SRMs for MSA-P, the shorter duration group, and the early-onset group were larger than were those for MSA-C, the longer duration group, and the late-onset group. SRMs for items regarding skilled hand activities, walking, and standing were relatively large. Our study indicates that the UMSARS (parts 2 and 4), SARA, and BBS are sensitive scales for evaluating MSA progression over 12 months. Items with large SRMs effectively evaluated short-term changes.

  14. Health-related quality of life in multiple system atrophy.

    PubMed

    Schrag, Anette; Geser, Felix; Stampfer-Kountchev, Michaela; Seppi, Klaus; Sawires, Martin; Köllensperger, Martin; Scherfler, Christoph; Quinn, Niall; Pellecchia, Maria T; Barone, Paolo; Del Sorbo, Francesca; Albanese, Alberto; Ostergaard, Karen; Dupont, Erik; Cardozo, Adriana; Tolosa, Eduardo; Nilsson, Christer F; Widner, Håkan; Lindvall, Olle; Giladi, Nir; Gurevich, Tanya; Daniels, Christine; Deuschl, Günther; Coelho, Miguel; Sampaio, Cristina; Abele, Michael; Klockgether, Thomas; Schimke, Nicole; Eggert, Karla M; Oertel, Wolfgang; Djaldetti, Ruth; Colosimo, Carlo; Meco, Giuseppe; Poewe, Werner; Wenning, Gregor K

    2006-06-01

    Although multiple system atrophy (MSA) is a neurodegenerative disorder leading to progressive disability and decreased life expectancy, little is known about patients' own evaluation of their illness and factors associated with poor health-related quality of life (Hr-QoL). We, therefore, assessed Hr-QoL and its determinants in MSA. The following scales were applied to 115 patients in the European MSA-Study Group (EMSA-SG) Natural History Study: Medical Outcome Study Short Form (SF-36), EQ-5D, Beck Depression Inventory (BDI), Mini-Mental state examination (MMSE), Unified MSA Rating Scale (UMSARS), Hoehn & Yahr (H&Y) Parkinson's disease staging scale, Composite Autonomic Symptom Scale (COMPASS), and Parkinson's Disease Sleep Scale (PDSS). Forty-six percent of patients had moderate to severe depression (BDI > or = 17); Hr-QoL scores on the SF-36 and EQ-5D were significantly impaired. Pain, the only domain with similar scores in MSA and published PD patients, was reported more frequently in patients with MSA-P (predominantly parkinsonian motor subtype) than MSA-C (predominantly cerebellar motor subtype; 76% vs. 50%; P = 0.005). Hr-QoL scores correlated most strongly with UMSARS motor, COMPASS, and BDI scores but not with MMSE scores, age at onset, or disease duration. The COMPASS and UMSARS activities of daily living scores were moderate-to-strong predictors for the SF-36 physical summary score and the BDI and UMSARS motor scores for the SF-36 mental summary score. This report is the first study to show that Hr-QoL is significantly impaired in MSA. Although not all possible factors related to impaired Hr-QoL in MSA could be assessed, autonomic dysfunction, motor impairment, and depression were most closely associated with poor Hr-QoL, and therapeutic management, therefore, should concentrate upon these aspects of the disease.

  15. Tremor in Multiple System Atrophy – a review

    PubMed Central

    Kaindlstorfer, Christine; Granata, Roberta; Wenning, Gregor Karl

    2013-01-01

    Background Multiple system atrophy (MSA) is a rare neurodegenerative movement disorder characterized by a rapidly progressive course. The clinical presentation can include autonomic failure, parkinsonism, and cerebellar signs. Differentiation from Parkinson’s disease (PD) is difficult if there is levodopa-responsive parkinsonism, rest tremor, lack of cerebellar ataxia, or mild/delayed autonomic failure. Little is known about tremor prevalence and features in MSA. Methods We performed a PubMed search to collect the literature on tremor in MSA and considered reports published between 1900 and 2013. Results Tremor is a common feature among MSA patients. Up to 80% of MSA patients show tremor, and patients with the parkinsonian variant of MSA are more commonly affected. Postural tremor has been documented in about half of the MSA population and is frequently referred to as jerky postural tremor with evidence of minipolymyoclonus on neurophysiological examination. Resting tremor has been reported in about one-third of patients but, in contrast to PD, only 10% show typical parkinsonian “pill-rolling” rest tremor. Some patients exhibit intention tremor associated with cerebellar dysmetria. In general, MSA patients can have more than one tremor type owing to a complex neuropathology that includes both the basal ganglia and pontocerebellar circuits. Discussion Tremor is not rare in MSA and might be underrecognized. Rest, postural, action and intention tremor can all be present, with jerky tremulous movements of the outstretched hands being the most characteristic. However, reviewing the data on tremor in MSA suggests that not every shaky movement satisfies tremor criteria; therefore, further studies are needed. PMID:24116345

  16. Multiple system atrophy: the application of genetics in understanding etiology

    PubMed Central

    Federoff, Monica; Schottlaender, Lucia V; Houlden, Henry; Singleton, Andrew

    2016-01-01

    Classically defined phenotypically by a triad of cerebellar ataxia, parkinsonism and autonomic dysfunction in conjunction with pyramidal signs, multiple system atrophy (MSA) is a rare and progressive neurodegenerative disease affecting an estimated 3-4 per every 100,000 individuals among adults 50-99 years of age. With a pathological hallmark of alpha-synuclein-immunoreactive glial cytoplasmic inclusions (GCIs; Papp-Lantos inclusions), MSA patients exhibit marked neurodegenerative changes in the striatonigral and/or olivopontocerebellar structures of the brain. As a member of the alpha-synucleinopathy family, which is defined by its well-demarcated alpha-synuclein-immunoreactive inclusions and aggregation, MSA’s clinical presentation exhibits several overlapping features with other members including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Given the extensive fund of knowledge regarding the genetic etiology of PD revealed within the past several years, a genetic investigation of MSA is warranted. While a current genome wide association (GWA) study is underway for MSA to further clarify the role of associated genetic loci and single nucleotide polymorphisms (SNPs), several cases have presented solid preliminary evidence of a genetic etiology. Naturally, genes and variants manifesting known associations with PD (and other phenotypically similar neurodegenerative disorders), including SNCA and MAPT, have been comprehensively investigated in MSA patient cohorts. More recently variants in COQ2 have been linked to MSA in the Japanese population although this finding awaits replication. Nonetheless, significant positive associations with subsequent independent replication studies have been scarce. With very limited information regarding genetic mutations or alterations in gene dosage as a cause of MSA, the search for novel risk genes, which may be in the form of common variants or rare variants, is the logical nexus for MSA research. We believe

  17. SHC2 gene copy number in multiple system atrophy (MSA).

    PubMed

    Ferguson, Marcus C; Garland, Emily M; Hedges, Lora; Womack-Nunley, Bethany; Hamid, Rizwan; Phillips, John A; Shibao, Cyndya A; Raj, Satish R; Biaggioni, Italo; Robertson, David

    2014-02-01

    Multiple system atrophy (MSA) is a sporadic, late onset, rapidly progressing neurodegenerative disorder, which is characterized by autonomic failure, together with Parkinsonian, cerebellar, and pyramidal motor symptoms. The pathologic hallmark is the glial cytoplasmic inclusion with α-synuclein aggregates. MSA is thus an α-synucleinopathy. Recently, Sasaki et al. reported that heterozygosity for copy number loss of Src homology 2 domain containing-transforming protein 2 (SHC2) genes (heterozygous SHC2 gene deletions) occurred in DNAs from many Japanese individuals with MSA. Because background copy number variation can be distinct in different human populations, we assessed SHC2 allele copy number in DNAs from a US cohort of individuals with MSA, to determine the contribution of SHC2 gene copy number variation in an American cohort followed at a US referral center for MSA. Our cohort included 105 carefully phenotyped individuals with MSA. We studied 105 well-characterized patients with MSA and 5 control subjects with reduced SHC2 gene copy number. We used two TaqMan Gene Copy Number Assays, to determine the copy number of two segments of the SHC2 gene that are separated by 27 kb. Assay results of DNAs from all of our 105 subjects with MSA showed 2 copies of both segments of their SHC2 genes. Our results indicate that SHC2 gene deletions underlie few, if any, cases of well-characterized MSA in the US population. This is in contrast to the Japanese experience reported by Sasaki et al., likely reflecting heterogeneity of the disease in different genetic backgrounds.

  18. Differential involvement of hypothalamic vasopressin neurons in multiple system atrophy.

    PubMed

    Benarroch, Eduardo E; Schmeichel, Ann M; Sandroni, Paola; Low, Phillip A; Parisi, Joseph E

    2006-10-01

    We sought to determine whether there is differential involvement of different groups of hypothalamic arginine-vasopressin (AVP) synthesizing neurons in multiple system atrophy (MSA). Hypothalamus was obtained from five subjects with clinical diagnosis of MSA confirmed neuropathologically and five age-matched controls. Sections were immunostained for AVP, and cells with visible nuclei were counted in the posterior portion of the paraventricular nucleus (PVNp), supraoptic nucleus (SON), magnocellular PVN and suprachiasmatic nucleus (SCN). Sections of the hypothalamus and medulla were also immunostained for tyrosine hydroxylase (TH). There was a significant loss of AVP neurons in the PVNp in MSA compared with controls (17 +/- 3 versus 59 +/- 10 cells/section, P < 0.01). There was preservation of AVP- and TH-immunoreactive neurons in the SON and magnocellular PVN in all MSA cases. In contrast, there was marked depletion of TH-immunoreactive fibres innervating these magnocellular AVP neurons, coincident with a loss of neurons in the A1 area (6 +/- 1 versus 13 +/- 1 cells/section, P < 0.01). There was loss of AVP neurons in the SCN in MSA compared with control cases (14 +/- 3 versus 71 +/- 16 cells/section, P < 0.02). Our results indicate that, in MSA, loss of AVP neurons in the PVNp may contribute to sympathetic failure, whereas loss of catecholaminergic input from the brainstem to the magnocellular AVP neurons may contribute to impaired AVP secretion in response to orthostatic stress. Loss of AVP neurons in the SCN may contribute to impaired circadian regulation of endocrine and autonomic functions.

  19. Treatment of multiple system atrophy using intravenous immunoglobulin

    PubMed Central

    2012-01-01

    Background Multiple system atrophy (MSA) is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG) in MSA. Methods This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS) was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment. Results Nine subjects were enrolled, and seven (2 women and 5 men, age range 55–64 years) completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p<0.05). Two participants dropped out from the study because of a non-threatening skin rash. The UMSARS-I (activities of daily living) and USMARS-II (motor functions) improved significantly post-treatment. UMSARS-I improved in all subjects (pre-treatment 23.9 ± 6.0 vs. post-treatment 19.0±5.9 (p=0.01). UMSARS-II improved in 5 subjects, was unchanged in 1 and worsened in 1 (pre-treatment 26.1±7.5 vs. post-treatment 23.3±7.3 (p=0.025). The MR imaging results were not different comparing pre- to post-treatment. Conclusions Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed. PMID:23116538

  20. Excessive daytime sleepiness in multiple system atrophy (SLEEMSA study).

    PubMed

    Moreno-López, Claudia; Santamaría, Joan; Salamero, Manuel; Del Sorbo, Francesca; Albanese, Alberto; Pellecchia, Maria Teresa; Barone, Paolo; Overeem, Sebastiaan; Bloem, Bastiaan; Aarden, Willemijn; Canesi, Margherita; Antonini, Angelo; Duerr, Susanne; Wenning, Gregor K; Poewe, Werner; Rubino, Alfonso; Meco, Giuseppe; Schneider, Susanne A; Bhatia, Kailash P; Djaldetti, Ruth; Coelho, Miguel; Sampaio, Cristina; Cochen, Valerie; Hellriegel, Helge; Deuschl, Günther; Colosimo, Carlo; Marsili, Luca; Gasser, Thomas; Tolosa, Eduardo

    2011-02-01

    Sleep disorders are common in multiple system atrophy (MSA), but the prevalence of excessive daytime sleepiness (EDS) is not well known. To assess the frequency and associations of EDS in MSA. Survey of EDS in consecutive patients with MSA and comparison with patients with Parkinson disease (PD) and individuals without known neurologic disease. Twelve tertiary referral centers. Eighty-six consecutive patients with MSA; 86 patients with PD matched for age, sex, and Hoehn and Yahr stage; and 86 healthy subject individuals matched for age and sex. Epworth Sleepiness Scale (ESS), modified ESS, Sudden Onset of Sleep Scale, Tandberg Sleepiness Scale, Pittsburgh Sleep Quality Index, disease severity, dopaminergic treatment amount, and presence of restless legs syndrome. Mean (SD) ESS scores were comparable in MSA (7.72 [5.05]) and PD (8.23 [4.62]) but were higher than in healthy subjects (4.52 [2.98]) (P < .001). Excessive daytime sleepiness (ESS score >10) was present in 28% of patients with MSA, 29% of patients with PD, and 2% of healthy subjects (P < .001). In MSA, in contrast to PD, the amount of dopaminergic treatment was not correlated with EDS. Disease severity was weakly correlated with EDS in MSA and PD. Restless legs syndrome occurred in 28% of patients with MSA, 14% of patients with PD, and 7% of healthy subjects (P < .001). Multiple regression analysis (with 95% confidence intervals obtained using nonparametric bootstrapping) showed that sleep-disordered breathing and sleep efficiency predicted EDS in MSA and amount of dopaminergic treatment and presence of restless legs syndrome in PD. More than one-quarter of patients with MSA experience EDS, a frequency similar to that encountered in PD. In these 2 conditions, EDS seems to be associated with different causes.

  1. Internal anal sphincter atrophy in patients with systemic sclerosis.

    PubMed

    Thoua, Nora M; Schizas, Alexis; Forbes, Alastair; Denton, Christopher P; Emmanuel, Anton V

    2011-09-01

    SSc is a connective tissue, multisystem disorder of unknown aetiology. The gastrointestinal tract (GIT) is affected in up to 90% of patients. The exact pathophysiology of GIT involvement is not known, but it is related to both neurogenic and myogenic abnormalities as well as possible vascular and ischaemic changes. Thinning of the internal anal sphincter (IAS) has been demonstrated in SSc with faecal incontinence. We aimed to investigate anal sphincter structure in patients with SSc. Forty-four SSc patients [24 symptomatic (Sx) and 20 asymptomatic (ASx)] and 20 incontinent controls (ICs) were studied. Patients underwent anorectal manometry and endoanal US. In the ICs, external anal sphincter defects were more common, but the IAS was less atrophic, evident by both atrophy scores and IAS thickness. There was no significant difference in atrophy scores [Sx: 2 (1.5-3) vs ASx: 2 (1-2)] or IAS thickness [Sx: 1.85 (1.5-2.3) vs ASx: 1.8 (1.7-2.25)] between the Sx and ASx SSc patients. Patients with SSc (both Sx and ASx) have thin and atrophic IAS, suggesting that IAS atrophy develops even in ASx patients and this may be amenable to treatment with sacral neuromodulation.

  2. Muscle atrophy

    MedlinePlus

    Muscle wasting; Wasting; Atrophy of the muscles ... There are two types of muscle atrophy: disuse and neurogenic. Disuse atrophy is caused by not using the muscles enough . This type of atrophy can often be ...

  3. [A Patient with Early-Stage Multiple System Atrophy Showing Augmented Nystagmus in Light].

    PubMed

    Oguri, Masayoshi; Nakamura, Yousuke; Hara, Ayako; Kitano, Hiroya; Motokura, Toru

    2015-04-01

    The ability to fix the eyes on a target, visual fixation, is important for the maintenance of equilibrium. The visual suppression (VS) test is one method of measuring the function of visual fixation. The test records caloric nystagmus by electrooculography, and the maximum slow phase velocity of caloric nystagmus in darkness is compared with the slow phase velocity in light with eyes fixed. Lesions of the cerebellum, brain stem, and cerebrum cause abnormalities of VS. We report a patient whose VS became a clue in the diagnosis of a disorder of the central nervous system. A 54-year-old man complained of dizziness, which gradually increased in frequency over 5 months. He visited several clinics, where vestibular neutritis and cervical spondylosis were suspected and treated without improvement. Although a pure-tone auditory test revealed bilateral normal hearing, a caloric test showed a weak response and VS was lost with augmentation of caloric nystagmus in light on both sides. Both eye tracking and optokinetic nystagmus tests were abnormal. Although magnetic resonance imaging showed no abnormalities, single photon emission computed tomography revealed decreased blood flow in the parietal area. VS of caloric nystagmus towards the side of a lesion is reduced or abolished after unilateral flocculus damage, and is abolished bilaterally after bilateral flocculus damage. In the case of a parietal lobe or pontine lesion, VS is strongly abolished, and even augmentation of caloric nystagmus may be observed. In the present case, the patient was diagnosed with multiple-system atrophy after onset of dizziness.

  4. Diagnosing central nervous system vasculitis in children.

    PubMed

    Cellucci, Tania; Benseler, Susanne M

    2010-12-01

    To review the current literature of childhood central nervous system vasculitis, and to discuss a tailored approach to diagnosis and treatment based on recent evidence. Primary angiitis of the central nervous system in children (cPACNS) is an increasingly recognized inflammatory brain disease with potentially devastating neurological consequences. The diagnostic approach should be tailored to the clinical presentation of the child with suspected cPACNS and should address the expanding spectrum of inflammatory and noninflammatory brain diseases with overlapping clinical features. New evidence has confirmed that elective brain biopsies in children have a higher diagnostic yield than in adults and improve our ability to diagnose angiography-negative cPACNS. Finally, observational studies have shown that early diagnosis and aggressive treatment lead to improved neurological outcomes and lower mortality rates in patients with cPACNS. This review summarizes the recent data on diagnosis, classification, treatment, and outcomes in cPACNS. Our improved understanding of cPACNS facilitates a tailored diagnostic approach that results in earlier diagnosis and initiation of therapy for this potentially reversible condition.

  5. [Multiple system atrophy: prognostic factors in the "MSA-Aquitaine" cohort].

    PubMed

    Krim, E; Yekhlef, F; Chrysostome, V; Ghorayeb, I; Tison, F

    2007-01-01

    Multiple system atrophy (MSA) is a common cause of atypical parkinsonism, of poor prognosis. MSA is associated with short survival but data stemming from clinical or pathological studies are sparse and contrasted. Factors predicting survival in MSA are not fully established. We investigated the survival and prognostic factors of MSA in the cohort "MSA-Aquitaine". This was a retrospective study of an unselected cohort of patients included throughout Aquitaine based on the Consensus Conference statement concerning MSA diagnostic criteria, with prospective follow-up on mortality. All patients received a standard clinical examination and disease history was collected through medical records and interviews of patients. Survival was ascertained by telephonic calls. From 1 November 1998 to 1 April 2002, we diagnosed 86 patients (43 men and 43 women) with "probable" or "possible" MSA. Median survival from study inclusion was 2.4 years and was 10.2 years from clinical onset, very similar to the other series. Low age at study, diabetes, dysphagia, Hoehn and Yahr stage 5 can predict shorter survival in patients with MSA. We confirm that the prognosis for MSA patients is poor and that some factors may predict shorter survival.

  6. Atrophy, hypertrophy, and hypoxemia induce transcriptional regulators of the ubiquitin proteasome system in the rat heart.

    PubMed

    Razeghi, Peter; Baskin, Kedryn K; Sharma, Saumya; Young, Martin E; Stepkowski, Stanislaw; Essop, M Faadiel; Taegtmeyer, Heinrich

    2006-04-07

    In skeletal muscle, transcript levels of proteins regulating the ubiquitin proteasome system (UPS) increase with atrophy and decrease with hypertrophy. Whether the same is true for heart muscle is not known. We set out to characterize the transcriptional profile of regulators of the UPS during atrophy-, hypertrophy-, and hypoxia-induced remodeling of the heart. Cardiac atrophy was induced by heterotopic transplantation of the rat heart. Left ventricular hypertrophy was induced by banding of the ascending aorta in rats. To study the effects of hypoxemia on the left ventricle, rats were exposed to hypobaric hypoxia. Transcript levels of six known regulators of the UPS, ubiquitin B (UbB), the ubiquitin conjugating enzymes UbcH2 and E2-14kDa, the ubiquitin ligases Mafbx/Atrogin-1 and MuRF-1, and the proteasomal subunit PSMB4 were measured using quantitative RT-PCR. Unloading-induced atrophy increased mRNA levels of UbB and decreased levels of both ubiquitin ligases. Transcript levels of all UPS genes investigated increased in the hypertrophied and hypoxic heart (with the exception of E2-14kDa). Cardiac atrophy, hypertrophy, and hypoxemia all increase myocardial UbB expression, suggesting that UbB is a transcriptional marker for load-induced and hypoxia-mediated cardiac remodeling.

  7. Atrophy, hypertrophy, and hypoxemia induce transcriptional regulators of the ubiquitin proteasome system in the rat heart

    USDA-ARS?s Scientific Manuscript database

    In skeletal muscle, transcript levels of proteins regulating the ubiquitin proteasome system (UPS) increase with atrophy and decrease with hypertrophy. Whether the same is true for heart muscle is not known. We set out to characterize the transcriptional profile of regulators of the UPS during atrop...

  8. Diagnosing Marital and Family Systems: A Training Model.

    ERIC Educational Resources Information Center

    Cromwell, Ronald E.; Keeney, Bradford P.

    1979-01-01

    A three-part training model in diagnosing marital and family systems is described. The first unit introduced diagnostic tools and techniques. The second focuses on family systems theory and its relation to diagnosis. The third integrates the derived theory of diagnosing marital and family systems with clinical application. (Author)

  9. Vaginal Atrophy

    MedlinePlus

    Vaginal atrophy Overview Vaginal atrophy (atrophic vaginitis) is thinning, drying and inflammation of the vaginal walls due to your body having less estrogen. Vaginal atrophy occurs most often after ...

  10. Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy.

    PubMed

    Brown, Richard G; Lacomblez, Lucette; Landwehrmeyer, Bernard G; Bak, Thomas; Uttner, Ingo; Dubois, Bruno; Agid, Yves; Ludolph, Albert; Bensimon, Gilbert; Payan, Christine; Leigh, Nigel P

    2010-08-01

    This article reports the severity and profile of neuropsychological impairment on a prevalent cohort of patients with a clinical diagnosis of either multiple system atrophy (n=372) or progressive supranuclear palsy (n=311) from the Neuroprotection and Natural History in Parkinson Plus Syndromes cohort. The Dementia Rating Scale and Frontal Assessment Battery were used to assess global cognition and executive dysfunction. For the Dementia Rating Scale impairment was observed in approximately 57% of the progressive supranuclear palsy group and 20% of the multiple system atrophy group. In the former, impairment in a single cognitive domain was observed in 40%, with the same number showing impairment in multiple domains, while in the latter the figures were 28.6 and 13.5%, respectively. On the Frontal Assessment Battery, impairment was observed in 62.0% of patients with progressive supranuclear palsy and 31.8% of those with multiple system atrophy. Although the progressive supranuclear palsy group performed worse overall, the cognitive profiles of the two groups on the Dementia Rating Scale subscales were identical, with the main impairment of the Initiation and Perseveration subscale. The impaired patients in the two groups were largely indistinguishable, qualitatively and quantitatively. Impairment was associated with greater age and clinical disability in both groups and was evident even in the early stages (22% in multiple system atrophy and 50% in progressive supranuclear palsy). Where a pathological diagnosis was available, the original clinical diagnosis was confirmed in the majority of cases, including those with significant cognitive impairment. The rate of impairment in those with a confirmed pathological diagnosis was comparable to that of the sample as a whole. These results demonstrate, in the largest prospectively recruited cohort of patients with progressive supranuclear palsy and multiple system atrophy studied to date, the existence of a cognitive

  11. Obsessive compulsive personality disorder in Progressive Supranuclear Palsy, Multiple System Atrophy and Essential Tremor.

    PubMed

    Nicoletti, A; Luca, A; Luca, M; Donzuso, G; Mostile, G; Raciti, L; Contrafatto, D; Dibilio, V; Sciacca, G; Cicero, C E; Vasta, R; Petralia, A; Zappia, M

    2016-09-01

    aim of the study was to evaluate the presence of the Obsessive Compulsive Personality Disorder (OCPeD) in Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP) and Essential Tremor (ET) and in a group of healthy subjects. patients affected by MSA, PSP and ET diagnosed according to currently accepted diagnostic criteria and a group of healthy controls were enrolled in the study. Patients with cognitive impairment were excluded from the study. The Structured Clinical Interview for Personality Disorders-II (SCID-II) has been performed to evaluate the presence of personality disorders (PeDs). The diagnosis of OCPeD was confirmed by a psychiatric interview. fifteen MSA patients (8 men and 7 women; aged 62.9 ± 7.6 years), 14 PSP patients (8 men and 6 women; aged 69.8 ± 4.4 years), 16 ET patients (10 men and 6 women; aged 70.4 ± 6.4 years) and 20 healthy subjects (10 men and 10 women; aged 65.5 ± 6.0 years) were enrolled. OCPeD was recorded in 5 (35.7%) PSP patients, 2 (13.3%) MSA patients, 2 (12.5%) ET patient and 2 (10%) controls. a low frequency of OCPeD, close to those recorded in healthy subjects, was recorded in both MSA and ET patients. Conversely an higher frequency of OCPeD, similar to PD was found among PSP patients, supporting the possibility of an impairment of common basal ganglia network possibly involving the orbito-frontal circuits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Slowed Prosaccades and Increased Antisaccade Errors As a Potential Behavioral Biomarker of Multiple System Atrophy

    PubMed Central

    Brooks, Sarah H.; Klier, Eliana M.; Red, Stuart D.; Mehta, Neeti D.; Patel, Saumil S.; Chuang, Alice Z.; Suescun, Jessika; Schiess, Mya C.; Sereno, Anne B.

    2017-01-01

    Current clinical diagnostic tools are limited in their ability to accurately differentiate idiopathic Parkinson’s disease (PD) from multiple system atrophy (MSA) and other parkinsonian disorders early in the disease course, but eye movements may stand as objective and sensitive markers of disease differentiation and progression. To assess the use of eye movement performance for uniquely characterizing PD and MSA, subjects diagnosed with PD (N = 21), MSA (N = 11), and age-matched controls (C, N = 20) were tested on the prosaccade and antisaccade tasks using an infrared eye tracker. Twenty of these subjects were retested ~7 months later. Saccade latencies, error rates, and longitudinal changes in saccade latencies were measured. Both PD and MSA patients had greater antisaccade error rates than C subjects, but MSA patients exhibited longer prosaccade latencies than both PD and C patients. With repeated testing, antisaccade latencies improved over time, with benefits in C and PD but not MSA patients. In the prosaccade task, the normal latencies of the PD group show that basic sensorimotor oculomotor function remain intact in mid-stage PD, whereas the impaired latencies of the MSA group suggest additional degeneration earlier in the disease course. Changes in antisaccade latency appeared most sensitive to differences between MSA and PD across short time intervals. Therefore, in these mid-stage patients, increased antisaccade errors combined with slowed prosaccade latencies might serve as a useful marker for early differentiation between PD and MSA, and, antisaccade performance, a measure of MSA progression. Together, our findings suggest that eye movements are promising biomarkers for early differentiation and progression of parkinsonian disorders. PMID:28676787

  13. Multiple System Atrophy with Orthostatic Hypotension (Shy-Drager Syndrome)

    MedlinePlus

    ... the onset of symptoms. A problem with the respiratory system is the most common cause of death. × Prognosis ... the onset of symptoms. A problem with the respiratory system is the most common cause of death. View ...

  14. [Clinical and imaging diagnostics of Parkinson's disease and multiple system atrophy].

    PubMed

    Schmidt, K I; Spiegel, J; Reith, W

    2011-04-01

    The diagnosis of Parkinson's disease (PD) and multiple system atrophy (MSA) is primarily made by clinical symptoms, but might still remain challenging even for experienced neurologists. Neuroradiologic imaging may be a useful tool in the diagnostic work-up, particularly for excluding other diseases, such as normal pressure hydrocephalus, multi-infarct dementia and cerebellar lesions. Nuclear medicine methods can additionally support the diagnosis and differential diagnosis of PD and MSA.

  15. Cognitive impairments in multiple system atrophy: MSA-C vs MSA-P.

    PubMed

    Kawai, Y; Suenaga, M; Takeda, A; Ito, M; Watanabe, H; Tanaka, F; Kato, K; Fukatsu, H; Naganawa, S; Kato, T; Ito, K; Sobue, G

    2008-04-15

    We evaluated comprehensive neuropsychological tests and regional brain blood flow to compare cognitive dysfunction between two types of multiple system atrophy: predominant cerebellar ataxia (MSA-C) and predominant parkinsonism (MSA-P). Twenty-one patients with MSA-C, 14 patients with MSA-P, and 21 age- and education-matched control subjects were subjected to neuropsychological tests and SPECT. The neuropsychological tests examined general cognition, verbal and visual memory, working memory, visuospatial and constructional ability, language, executive function, depression, and anxiety, while SPECT analysis examined brain perfusion. Patients with MSA-P showed severe involvement of visuospatial and constructional function, verbal fluency, and executive function compared with control subjects. Patients with MSA-C showed involvement only in visuospatial and constructional function compared with control subjects and a milder degree of involvement compared with patients with MSA-P. Patients with MSA-P tended toward a wide and severe impairment in cognitive function compared with patients with MSA-C. In addition, neuropsychological impairment in patients with MSA-P was significantly correlated with a decrease in prefrontal perfusion. This significant relation was not correlated to other factors such as age, education, and severity of cerebellar ataxia and parkinsonism, which are relevant factors associated with cognitive performance. Patients with multiple system atrophy-parkinsonism show more severe and more widespread cognitive dysfunctions than patients with multiple system atrophy-cerebellar ataxia. Our results also indicate that cognitive dysfunction in patients with multiple system atrophy-parkinsonism may be associated with prefrontal involvement.

  16. Erythropoietin is Neuroprotective in a Transgenic Mouse Model of Multiple System Atrophy

    PubMed Central

    Pallua, Anton; Stefanova, Nadia; Poewe, Werner; Wenning, Gregor K.

    2016-01-01

    Multiple system atrophy is a rapidly progressive neurodegenerative disorder with a markedly reduced life expectancy. Failure of symptomatic treatment raises an urgent need for disease-modifying strategies. We have investigated the neuroprotective potential of erythropoietin in (proteolipid protein)-α-synuclein transgenic mice exposed to 3-nitropropionic acid featuring multiple system atrophy-like pathology including oligodendroglial α-synuclein inclusions and selective neuronal degeneration. Mice were treated with erythropoietin starting before (early erythropoietin) and after (late erythropoietin) intoxication with 3-nitropropionic acid. Nonintoxicated animals receiving erythropoietin and intoxicated animals treated with saline served as control groups. Behavioral tests included pole test, open field activity, and motor behavior scale. Immunohistochemistry for tyrosine hydroxylase and dopamine and cyclic adenosine monophosphate-regulated phosphoprotein (DARPP-32) was analyzed stereologically. Animals receiving erythropoietin before and after 3-nitropropionic acid intoxication scored significantly lower on the motor behavior scale and they performed better in the pole test than controls with no significant difference between early and late erythropoietin administration. Similarly, rearing scores were worse in 3-nitropropionic acid-treated animals with no difference between the erythropoietin subgroups. Immunohistochemistry revealed significant attenuation of 3-nitropropionic acid-induced loss of tyrosine hydroxylase and DARPP-32 positive neurons in substantia nigra pars compacta and striatum, respectively, in both erythropoietin-treated groups without significant group difference in the substantia nigra. However, at striatal level, a significant difference between early and late erythropoietin administration was observed. In the combined (proteolipid protein)-α-synuclein 3-nitropropionic acid multiple system atrophy mouse model, erythropoietin appears to rescue

  17. Laryngeal stridor in multiple system atrophy: Clinicopathological features and causal hypotheses.

    PubMed

    Ozawa, Tetsutaro; Sekiya, Kanako; Aizawa, Naotaka; Terajima, Kenshi; Nishizawa, Masatoyo

    2016-02-15

    Laryngeal stridor is recognized as a characteristic clinical manifestation in patients with multiple system atrophy (MSA). However, the pathogenic mechanisms underlying this symptom are controversial. Neurogenic atrophy of the posterior cricoarytenoid muscle has been identified in cases of MSA, suggesting that laryngeal abductor weakness contributes to laryngeal stridor. However, dystonia in the laryngeal adductor muscles has also been reported to cause laryngeal stridor. Depletion of serotonergic neurons in the medullary raphe nuclei, which exert tonic drive to activate the posterior cricoarytenoid muscle, has recently been identified in MSA cases. This adds weight to the possibility that laryngeal abductor weakness underlies laryngeal stridor in MSA. Continuous positive airway pressure therapy is currently used in the treatment of laryngeal stridor, but should be used with caution in patients showing contraindications. Current knowledge of the clinical and neuropathological features of laryngeal stridor is summarized in this paper, and the hypothesized causes and possible therapeutic options for this symptom are discussed.

  18. Quantifying cerebellar atrophy in multiple system atrophy of the cerebellar type (MSA-C) using three-dimensional gyrification index analysis.

    PubMed

    Wu, Yu-Te; Shyu, Kuo-Kai; Jao, Chii-Wen; Liao, Yuan-Lin; Wang, Tzu-Yun; Wu, Hsiu-Mei; Wang, Po-Shan; Soong, Bing-Wen

    2012-05-15

    Multiple system atrophy of the cerebellar type (MSA-C) is a degenerative neurological disease of the central nervous system. This study employed a method named, "surface-based three-dimensional gyrification index" (3D-GI) to quantify morphological changes in normal cerebellum (including brainstem) and atrophied cerebellum, in patients with MSA-C. We assessed whether 3D-GI can exclude gender and age differences to quantify cerebellum and brainstem atrophy more accurately. Sixteen healthy subjects and 16 MSA-C patients participated in this study. We compared 3D-GI values and volumes in the cerebellum, based on T1-weighted MR images. We also compared the images of reconstructed 3D cerebellum gray matter (3D-CBGM) and cerebellum white matter (3D-CBWM) to detect the atrophied cerebellar region in MSA-C patients. The 3D-GI values were in a stable range with small variances, exhibiting no gender effect and no age-related shrinkage. Significantly lower 3D-GI values were exhibited in both CBGM and CBWM of the MSA-C patients compared with healthy subjects, even in the early phases of the disease. Decreases in 3D-GI values indicated the degeneration of the cerebellar folding structure, exactly reflecting the morphological changes in cerebellum. The 3D-GI method based on CBGM resulted in superior discriminative accuracy compared with the CBGM volumetric method. Using the two-dimensional 3D-GI values, the K-means classifier can evidently discriminate the MSA-C patients from healthy subjects.

  19. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson's disease.

    PubMed

    Antonini, A; Leenders, K L; Vontobel, P; Maguire, R P; Missimer, J; Psylla, M; Günther, I

    1997-12-01

    We used PET with the tracers [18F]fluorodeoxyglucose (FDG), [18F]fluorodopa (FDOPA) and [11C]raclopride (RACLO) to study striatal glucose and dopa metabolism, and dopamine D2 receptor binding, respectively, in nine patients with multiple system atrophy. Ten patients with classical Parkinson's disease were investigated with the same three PET tracers' and three separate groups, each of 10 healthy subjects, served as control populations. We found that striatal FDOPA values separated all healthy subjects from patients with parkinsonism but they were not useful in distinguishing multiple system atrophy from Parkinson's disease. Conversely, striatal RACLO as well as FDG values discriminated all multiple system atrophy from Parkinson's disease patients as well as from healthy control subjects. Metabolic and receptor binding decrements in the putamen of multiple system atrophy patients were significantly correlated. Stepwise regression analysis revealed that a linear combination of putamen RACLO and FDOPA values accurately predicted clinical measures of disease severity in the multiple system atrophy group. Our findings suggest that striatal FDG and particularly RACLO are sensitive and effective measures of striatal function and may help characterizing patients with multiple system atrophy. In contrast, FDOPA measurements are accurate in detecting abnormalities of the nigrostriatal dopaminergic system but may not distinguish among different forms of parkinsonism.

  20. Survival of patients with pathologically proven multiple system atrophy: a meta-analysis.

    PubMed

    Ben-Shlomo, Y; Wenning, G K; Tison, F; Quinn, N P

    1997-02-01

    A systematic review of the neurologic literature identified 433 cases of pathologically proven multiple system atrophy over a 100-year period. Earlier case reports included patients younger in age with more frequent cerebellar involvement. Mean age of onset was 54.2 years (range 31 to 78) and survival was 6.2 years (range 0.5 to 24). Survival analysis showed a secular trend from a median duration of 4.9 years for publications between 1887 and 1970 to 6.8 years between 1991 and 1994. Older age of onset was associated with shorter survival; the hazard ratio for patients with onset after 60 years was 1.8 (95% CI 1.4 to 2.3) compared with patients between 31 and 49 years. Cerebellar features were associated with marginally increased survival (6.1 years versus 5.4 years; p = 0.04). There were no difference in survival according to gender, parkinsonian, or pyramidal features or whether the patient was classified as striatonigral degeneration or olivopontocerebellar atrophy type. These results demonstrate the poor prognosis for patients with multiple system atrophy but may be biased toward the worst cases. Future research needs to recruit more representative samples.

  1. Multiple-System Atrophy with Cerebellar Predominance Presenting as Respiratory Insufficiency and Vocal Cords Paralysis

    PubMed Central

    de Mello, Ramon Andrade Bezerra; Ferreira, Diana; Dias da Costa, José Manuel; Rosas, Maria José; Quinaz, João Manuel

    2010-01-01

    Background. MSA (Multiple System Atrophy) may be associated either with Parkinsonism or with cerebellar ataxia (MSA-c subtype). It is considered a rare disease, but many patients are misdiagnosed as suffering from idiopathic Parkinson's disease. In this paper, we report a case of a patient admitted with respiratory failure and vocal cords paralysis due to MSA-c. Case Report. A 79-year-old Caucasian woman was admitted in March 2010 with dyspnea, asthenia, stridor, and respiratory failure needing noninvasive ventilation. She had orthostatic blood pressure decline, constipation, insomnia, daytime sleepiness, and snoring. The neurologic examination revealed cerebellar ataxia. A laryngoscopy revealed vocal cord paralysis in midline position and tracheostomy was performed. The Brain Magnetic Resonance Imaging revealed atrophy of middle cerebellar peduncles and pons with the “hot cross bun sign.” Conclusion. Although Multiple-system atrophy is a rare disease, unexplained respiratory failure, bilateral vocal cord paralysis, or stridor should lead to consider MSA as diagnosis. PMID:20862340

  2. Diagnosing the PEP-II Injection System

    SciTech Connect

    Decker, F.-J.; Donald, M.H.; Iverson, R.H.; Kulikov, A.; Pappas, G.C.; Weaver, M.; /SLAC

    2005-05-09

    The injection of beam into the PEP-II B-Factory, especially into the High Energy Ring (HER) has some challenges. A high background level in the BaBar detector has for a while inhibited us from trickling charge into the HER similar to the Low Energy Ring (LER). Analyzing the injection system has revealed many issues which could be improved. The injection bump between two kickers was not closed, mainly because the phase advance wasn't exactly 180{sup o} and the two kicker strengths were not balanced. Additionally we found reflections which kick the stored beam after the main kick and cause the average luminosity to drop about 3% for a 10 Hz injection rate. The strength of the overall kick is nearly twice as high as the design, indicating a much bigger effective septum thickness. Compared with single beam the background is worse when the HER beam is colliding with the LER beam. This hints that the beam-beam force and the observed vertical blow-up in the HER pushes the beam and especially the injected beam further out to the edge of the dynamic aperture or beyond.

  3. [Atrophy in the mucosa neighboring an intestinal-type gastric adenocarcinoma by comparing the Sydney vs. OLGA systems].

    PubMed

    Ramírez-Mendoza, Pablo; Hernández-Briseño, Liliana; Casarrubias-Ramírez, Moisés; Alvarado-Cabrero, Isabel; Ángeles-Garay, Ulises

    2015-01-01

    Gastric carcinoma causes about 700 000 deaths worldwide per year. Is feasible detect it in earlier stages. The aim of this article is to assess the atrophy in the mucosa neighboring an intestinal-type gastric adenocarcinoma by comparing the Sydney vs. OLGA systems. Twenty-eight individuals with intestinal-type gastric adenocarcinoma (Lauren) were compared with 32 non-neoplastic cases. Both groups had undergone total gastrectomy. Two pathologists made a consensus-based assessment of the atrophy in non-neoplastic corpus and antral epithelium using the Sydney and OLGA Systems. The mean, median, and distribution of the frequencies were obtained using the measuring and distribution scales of the study variables. The sensitivity, specificity, and predictive values, both positive and negative, for gastric cancer were calculated through the dichotomy of advanced atrophy-positive and advanced atrophy-negative scales. Twenty-four of the 28 cases with intestinal-type gastric carcinoma showed an advanced atrophy with the OLGA system, with a sensitivity and specificity of 77 and 85 %, respectively. Conversely, 4 of the 28 individuals showed an advanced atrophy with the Sydney system, with a sensitivity and specificity of 14 and 100 %, respectively. The OLGA system has a high sensitivity and specificity (77 y 85 % respectively) for the recognition of preneoplastic changes in the mucosa neighboring a gastric carcinoma.

  4. [Prognostic factors for inability to walk independently in patients with multiple system atrophy].

    PubMed

    Wang, Z W; Wu, X H; Qiu, F; Liu, J G; Yao, W; Jiang, M; Wang, S S; Chen, Z G; Qi, X K

    2017-02-01

    Objective: To explore the prognostic factors for inability to walk independently in patients with multiple system atrophy (MSA). Methods: A total of 123 patients with clinically confirmed MSA admitted to Navy General Hospital and Dongfang Hospital affiliated to the Second Clinical Medical College of Beijing University of Chinese Medicine, from February 2013 to February 2016, were retrospectively reviewed. Clinical data and all records were collected and all subjects were followed up by a telephone call in February 2016. The second milestone of activities of daily living scale (ADL), defined as inability to walk independently, was taken as the primary outcome. Eight possible prognostic factors were investigated and the survival analysis was performed with Cox proportional hazards model regression. Results: Of all the MSA patients, 74 subjects were men and 49 were women with a sex radio of 1.51∶1(M∶F). Seventy cases were diagnosed with MSA-cerebellar type (MSA-C) and 53 with MSA-Parkinson type (MSA-P) (C∶P=1.32∶1). Mean age at the onset of first symptom was (53±8) years old. All patients had severe autonomic nervous dysfunction. At the last follow-up, 56 cases (45.5%) were unable to walk independently. The median survival time from the onset of MSA to inability to walk independently was 73 months. The age of onset ≥ 55 years (HR=1.969, 95%CI 1.095-3.542, P=0.024) and the interval time from disease onset to combined motor and autonomic involvement≤3 years (HR=2.308, 95%CI 1.158-4.600, P=0.017) were independent prognostic factors for inability to walk independently, while gender, MSA clinical subtypes, initial symptoms, alcohol intake, smoking and toxic exposure were not indicators for independent walking (P>0.05). Conclusions: The prognostic factors for inability to walk independently in patients with MSA are the age of onset ≥55 years and the interval time from disease onset to combined motor and autonomic involvement≤3 years. Although factors

  5. A Testing System for Diagnosing Misconceptions in DC Electric Circuits.

    ERIC Educational Resources Information Center

    Chang, Kuo-En; Liu, Sei-Hua; Chen, Sei-Wang

    1998-01-01

    Outlines a test-based diagnosis system for misconceptions in DC electric circuits and its three parts: problem library, problem selector and diagnoser. Discusses misconception discrimination and diagnosis theories, and reports the system supports satisfactory diagnosis. Includes an analysis of nine student misconceptions about electrical circuits…

  6. Subclinical nigrostriatal dopaminergic denervation in the cerebellar subtype of multiple system atrophy (MSA-C).

    PubMed

    Muñoz, Esteban; Iranzo, Alex; Rauek, Sebastian; Lomeña, Francisco; Gallego, Judith; Ros, Doménec; Santamaría, Joan; Tolosa, Eduardo

    2011-12-01

    Nigrostriatal involvement is considered an additional feature in the new consensus criteria for the diagnosis of the cerebellar variant of multiple system atrophy (MSA-C). However, so far, only a few studies, which include a relative small number of patients, give support to this criterion. Our objective was to assess nigrostriatal dopaminergic innervation in patients with MSA-C without parkinsonism by use of dopamine transporter single photon emission computed tomography (DAT SPECT). Thirteen patients that fulfilled criteria for possible or probable MSA-C and presented no parkinsonian signs, and 12 age-matched healthy controls underwent ((123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ([(123)I]FP-CIT) SPECT. Patients were also evaluated through the Unified Multiple System Atrophy Rating Scale (UMSARS) and brain magnetic resonance imaging (MRI). The mean duration of the cerebellar syndrome was 3.8 ± 1.7 years. DAT SPECT showed a significant decrease of striatal [(123)I]FP-CIT uptake ratios in patients (p < 0.001). Radiotracer uptake reduction was 21% in the entire striatum, 19% in putamen, and 24% in caudate nuclei. Striatal binding ratios were within the normal range in 3 patients. We did not find correlation between striatal uptake and disease duration, age of patients, UMSARS-II score, and pontine diameter. [(123)I]FP-CIT SPECT shows that most but not all MSA-C patients without parkinsonism have subclinical nigrostriatal dopaminergic denervation which is not related to disease duration, cerebellar dysfunction, or pontine atrophy.

  7. Quantitative analysis of structural variations in corpus callosum in adults with multiple system atrophy (MSA)

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Debanjali; Sinha, Neelam; Saini, Jitender

    2017-03-01

    Multiple system atrophy (MSA) is a rare, non-curable, progressive neurodegenerative disorder that affects nervous system and movement, poses a considerable diagnostic challenge to medical researchers. Corpus callosum (CC) being the largest white matter structure in brain, enabling inter-hemispheric communication, quantification of callosal atrophy may provide vital information at the earliest possible stages. The main objective is to identify the differences in CC structure for this disease, based on quantitative analysis on the pattern of callosal atrophy. We report results of quantification of structural changes in regional anatomical thickness, area and length of CC between patient-groups with MSA with respect to healthy controls. The method utilizes isolating and parcellating the mid-sagittal CC into 100 segments along the length - measuring the width of each segment. It also measures areas within geometrically defined five callosal compartments of the well-known Witelson, and Hofer-Frahma schemes. For quantification, statistical tests are performed on these different callosal measurements. From the statistical analysis, it is concluded that compared to healthy controls, width is reduced drastically throughout CC for MSA group and as well as changes in area and length are also significant for MSA. The study is further extended to check if any significant difference in thickness is found between the two variations of MSA, Parkinsonian MSA and Cerebellar MSA group, using the same methodology. However area and length of this two sub-MSA group, no substantial difference is obtained. The study is performed on twenty subjects for each control and MSA group, who had T1-weighted MRI.

  8. The improvement of movement and speech during rapid eye movement sleep behaviour disorder in multiple system atrophy.

    PubMed

    De Cock, Valérie Cochen; Debs, Rachel; Oudiette, Delphine; Leu, Smaranda; Radji, Fatai; Tiberge, Michel; Yu, Huan; Bayard, Sophie; Roze, Emmanuel; Vidailhet, Marie; Dauvilliers, Yves; Rascol, Olivier; Arnulf, Isabelle

    2011-03-01

    Multiple system atrophy is an atypical parkinsonism characterized by severe motor disabilities that are poorly levodopa responsive. Most patients develop rapid eye movement sleep behaviour disorder. Because parkinsonism is absent during rapid eye movement sleep behaviour disorder in patients with Parkinson's disease, we studied the movements of patients with multiple system atrophy during rapid eye movement sleep. Forty-nine non-demented patients with multiple system atrophy and 49 patients with idiopathic Parkinson's disease were interviewed along with their 98 bed partners using a structured questionnaire. They rated the quality of movements, vocal and facial expressions during rapid eye movement sleep behaviour disorder as better than, equal to or worse than the same activities in an awake state. Sleep and movements were monitored using video-polysomnography in 22/49 patients with multiple system atrophy and in 19/49 patients with Parkinson's disease. These recordings were analysed for the presence of parkinsonism and cerebellar syndrome during rapid eye movement sleep movements. Clinical rapid eye movement sleep behaviour disorder was observed in 43/49 (88%) patients with multiple system atrophy. Reports from the 31/43 bed partners who were able to evaluate movements during sleep indicate that 81% of the patients showed some form of improvement during rapid eye movement sleep behaviour disorder. These included improved movement (73% of patients: faster, 67%; stronger, 52%; and smoother, 26%), improved speech (59% of patients: louder, 55%; more intelligible, 17%; and better articulated, 36%) and normalized facial expression (50% of patients). The rate of improvement was higher in Parkinson's disease than in multiple system atrophy, but no further difference was observed between the two forms of multiple system atrophy (predominant parkinsonism versus cerebellar syndrome). Video-monitored movements during rapid eye movement sleep in patients with multiple system

  9. An Expert System for Diagnosing Children's Multiplication Errors.

    ERIC Educational Resources Information Center

    Attisha, M.; Yazdani, M.

    1984-01-01

    Describes a microcomputer-based system for diagnosing children's multiplication errors which incorporates the knowledge base of all known systematic multiplication errors, and utilizes a modular approach to cope with the program's complexity. Each module's function, how the programs interact, and the design of pupil-machine interaction are…

  10. Autonomic nervous system testing may not distinguish multiple system atrophy from Parkinson's disease

    PubMed Central

    Riley, D; Chelimsky, T

    2003-01-01

    Background: Formal laboratory testing of autonomic function is reported to distinguish between patients with Parkinson's disease and those with multiple system atrophy (MSA), but such studies segregate patients according to clinical criteria that select those with autonomic dysfunction for the MSA category. Objective: To characterise the profiles of autonomic disturbances in patients in whom the diagnosis of Parkinson's disease or MSA used criteria other than autonomic dysfunction. Methods: 47 patients with parkinsonism and autonomic symptoms who had undergone autonomic laboratory testing were identified and their case records reviewed for non-autonomic features. They were classified clinically into three diagnostic groups: Parkinson's disease (19), MSA (14), and uncertain (14). The performance of the patients with Parkinson's disease was compared with that of the MSA patients on five autonomic tests: RR variation on deep breathing, heart rate changes with the Valsalva manoeuvre, tilt table testing, the sudomotor axon reflex test, and thermoregulatory sweat testing. Results: None of the tests distinguished one group from the other with any statistical significance, alone or in combination. Parkinson's disease and MSA patients showed similar patterns of autonomic dysfunction on formal testing of cardiac sympathetic and parasympathetic, vasomotor, and central and peripheral sudomotor functions. Conclusions: This study supports the clinical observation that Parkinson's disease is often indistinguishable from MSA when it involves the autonomic nervous system. The clinical combination of parkinsonism and dysautonomia is as likely to be caused by Parkinson's disease as by MSA. Current clinical criteria for Parkinson's disease and MSA that direct patients with dysautonomia into the MSA group may be inappropriate. PMID:12486267

  11. Clinical outcomes of two main variants of progressive supranuclear palsy and multiple system atrophy: a prospective natural history study.

    PubMed

    Jecmenica-Lukic, Milica; Petrovic, Igor N; Pekmezovic, Tatjana; Kostic, Vladimir S

    2014-08-01

    Progressive supranuclear palsy (PSP) and parkinsonian subtype of multiple system atrophy (MSA-P) are, after Parkinson's disease (PD), the most common forms of neurodegenerative parkinsonism. Clinical heterogeneity of PSP includes two main variants, Richardson syndrome (PSP-RS) and PSP-parkinsonism (PSP-P). Clinical differentiation between them may be impossible at least during the first 2 years of the disease. Little is known about the differences in natural course of PSP-RS and PSP-P and, therefore, in this study we prospectively followed the clinical outcomes of consecutive, pathologically unconfirmed patients with the clinical diagnoses of PSP-RS (51 patients), PSP-P (21 patients) and MSA-P (49 patients). Estimated mean survival time was 11.2 years for PSP-P, 6.8 years for PSP-RS, and 7.9 years for MSA-P, where a 5-year survival probabilities were 90, 66 and 78 %, respectively. More disabling course of PSP-RS compared to PSP-P was also highlighted through the higher number of milestones reached in the first 3 years of the disease, as well as in the trend to reach all clinical milestones earlier. We found that PSP-P variant had a more favorable course with longer survival, not only when compared to PSP-RS, but also when compared to another form of atypical parkinsonism, MSA-P.

  12. Obestatin controls the ubiquitin-proteasome and autophagy-lysosome systems in glucocorticoid-induced muscle cell atrophy.

    PubMed

    Cid-Díaz, Tania; Santos-Zas, Icía; González-Sánchez, Jessica; Gurriarán-Rodríguez, Uxía; Mosteiro, Carlos S; Casabiell, Xesús; García-Caballero, Tomás; Mouly, Vincent; Pazos, Yolanda; Camiña, Jesús P

    2017-07-03

    Many pathological states characterized by muscle atrophy are associated with an increase in circulating glucocorticoids and poor patient prognosis, making it an important target for treatment. The development of treatments for glucocorticoid-induced and wasting disorder-related skeletal muscle atrophy should be designed based on how the particular transcriptional program is orchestrated and how the balance of muscle protein synthesis and degradation is deregulated. Here, we investigated whether the obestatin/GPR39 system, an autocrine/paracrine signaling system acting on myogenesis and with anabolic effects on the skeletal muscle, could protect against glucocorticoid-induced muscle cell atrophy. In the present study, we have utilized mouse C2C12 myotube cultures to examine whether the obestatin/GPR39 signaling pathways can affect the atrophy induced by the synthetic glucocorticoid dexamethasone. We have extended these findings to in vitro effects on human atrophy using human KM155C25 myotubes. The activation of the obestatin/GPR39 system protects from glucocorticoid-induced atrophy by regulation of Akt, PKD/PKCμ, CAMKII and AMPK signaling and its downstream targets in the control of protein synthesis, ubiquitin-proteasome system and autophagy-lysosome system in mouse cells. We compared mouse and human myotube cells in their response to glucocorticoid and identified differences in both the triggering of the atrophic program and the response to obestatin stimulation. Notably, we demonstrate that specific patterns of post-translational modifications of FoxO4 and FoxO1 play a key role in directing FoxO activity in response to obestatin in human myotubes. Our findings emphasize the function of the obestatin/GPR39 system in coordinating a variety of pathways involved in the regulation of protein degradation during catabolic conditions. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on

  13. Reduced fractional anisotropy in early-stage cerebellar variant of multiple system atrophy.

    PubMed

    Oishi, Kenichi; Konishi, Junya; Mori, Susumu; Ishihara, Hiroyuki; Kawamitsu, Hideaki; Fujii, Masahiko; Kanda, Fumio

    2009-04-01

    In patients with the cerebellar variant of multiple system atrophy (MSA-C), reduced fractional anisotropy (FA) has been reported in several brain areas. However, since previous studies have employed predetermined regions of interest (ROI), the brain areas showing the earliest alterations in FA are unknown. The sensitivity of detecting early-stage MSA-C and the time course of the FA reduction are also unknown. The purpose was to address these issues to determine the diagnostic value of FA for early diagnosis. Twenty-one patients with MSA-C were investigated. Voxel-based FA analysis and morphometry were used to detect the differences between early-stage MSA-C and normal controls. An ROI-based FA analysis was also used to clarify the temporal profile. From the early-stage, MSA-C patients exhibited reduced FA and white matter atrophy in the middle cerebellar peduncle, the inferior cerebellar peduncle, and the ventral pons. The FA of these areas decreased rapidly during the first few years after onset, after which a rather gradual reduction occurred. The receiver operating characteristics analysis revealed a high sensitivity and specificity for discriminating early MSA-C from normal controls. FA measurement could potentially be used to make an early diagnosis and monitor progression in MSA-C patients.

  14. Myeloperoxidase inhibition ameliorates multiple system atrophy-like degeneration in a transgenic mouse model.

    PubMed

    Stefanova, Nadia; Georgievska, Biljana; Eriksson, Håkan; Poewe, Werner; Wenning, Gregor K

    2012-05-01

    Multiple system atrophy (MSA) is a rare and fatal α-synucleinopathy characterized by a distinctive oligodendrogliopathy with glial cytoplasmic inclusions and associated neuronal multisystem degeneration. The majority of patients presents with a rapidly progressive parkinsonian disorder and atypical features such as early autonomic failure and cerebellar ataxia. We have previously reported that complete MSA pathology can be modeled in transgenic mice overexpressing oligodendroglial α-synuclein under conditions of oxidative stress induced by 3-nitropropionic acid (3-NP) including striatonigral degeneration, olivopontocerebellar atrophy, astrogliosis, and microglial activation. Here, we show that myeloperoxidase (MPO), a key enzyme involved in the production of reactive oxygen species by phagocytic cells, is expressed in both human and mouse MSA brains. We also demonstrate that in the MSA mouse model, MPO inhibition reduces motor impairment and rescues vulnerable neurons in striatum, substantia nigra pars compacta, cerebellar cortex, pontine nuclei, and inferior olives. MPO inhibition is associated with suppression of microglial activation but does not affect 3-NP induced astrogliosis in the same regions. Finally, MPO inhibition results in reduced intracellular aggregates of α-synuclein. This study suggests that MPO inhibition may represent a novel candidate treatment strategy against MSA-like neurodegeneration acting through its anti-inflammatory and anti-oxidative properties. © Springer Science+Business Media, LLC 2011

  15. Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients

    PubMed Central

    Schottlaender, Lucia V.; Bettencourt, Conceição; Kiely, Aoife P.; Chalasani, Annapurna; Neergheen, Viruna; Holton, Janice L.; Hargreaves, Iain; Houlden, Henry

    2016-01-01

    Background The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases. Methods Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as well as idiopathic Parkinson's disease (n = 7), dementia with Lewy bodies (n = 20), corticobasal degeneration (n = 15) and cerebellar ataxia (n = 18) patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography. Results We detected a statistically significant decrease (by 3–5%) in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001), specifically in OPCA (P = 0.001) and mixed cases (P = 0.005), when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001), idiopathic Parkinson's disease (P<0.001), corticobasal degeneration (P<0.001), and cerebellar ataxia (P = 0.001)]. Conclusion Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated. PMID:26894433

  16. Vulvovaginal Atrophy

    PubMed Central

    Mac Bride, Maire B.; Rhodes, Deborah J.; Shuster, Lynne T.

    2010-01-01

    Vulvovaginal atrophy (VVA) is a common and underreported condition associated with decreased estrogenization of the vaginal tissue. Symptoms include dryness, irritation, soreness, and dyspareunia with urinary frequency, urgency, and urge incontinence. It can occur at any time in a woman's life cycle, although more commonly in the postmenopausal phase, during which the prevalence is close to 50%. Clinical findings include the presence of pale and dry vulvovaginal mucosa with petechiae. Vaginal rugae disappear, and the cervix may become flush with the vaginal wall. A vaginal pH of 4.6 or more supports the diagnosis of VVA. Even while taking systemic estrogen, 10% to 20% of women may still have residual VVA symptoms. Breast cancer treatment increases the prevalence of VVA because the surgical, endocrine, and chemotherapeutic agents used in its treatment can cause or exacerbate VVA. Local estrogen treatment for this group of women remains controversial. PMID:20042564

  17. MOORE: A prototype expert system for diagnosing spacecraft problems

    NASA Technical Reports Server (NTRS)

    Howlin, Katherine; Weissert, Jerry; Krantz, Kerry

    1988-01-01

    MOORE is a rule-based, prototype expert system that assists in diagnosing operational Tracking and Data Relay Satellite (TDRS) problems. It is intended to assist spacecraft engineers at the TDRS ground terminal in trouble shooting problems that are not readily solved with routine procedures, and without expert counsel. An additional goal of the prototype system is to develop in-house expert system and knowledge engineering skills. The prototype system diagnoses antenna pointing and earth pointing problems that may occur within the TDRS Attitude Control System (ACS). Plans include expansion to fault isolation of problems in the most critical subsystems of the TDRS spacecraft. Long term benefits are anticipated with use of an expert system during future TDRS programs with increased mission support time, reduced problem solving time, and retained expert knowledge and experience. Phase 2 of the project is intended to provide NASA the necessary expertise and capability to define requirements, evaluate proposals, and monitor the development progress of a highly competent expert system for NASA's Tracking Data Relay Satellite. Phase 2 also envisions addressing two unexplored applications for expert systems, spacecraft integration and tests (I and T) and support to launch activities. The concept, goals, domain, tools, knowledge acquisition, developmental approach, and design of the expert system. It will explain how NASA obtained the knowledge and capability to develop the system in-house without assistance from outside consultants. Future plans will also be presented.

  18. MOORE: A prototype expert system for diagnosing spacecraft problems

    NASA Technical Reports Server (NTRS)

    Howlin, Katherine; Weissert, Jerry; Krantz, Kerry

    1988-01-01

    MOORE is a rule-based, prototype expert system that assists in diagnosing operational Tracking and Data Relay Satellite (TDRS) problems. It is intended to assist spacecraft engineers at the TDRS ground terminal in trouble shooting problems that are not readily solved with routine procedures, and without expert counsel. An additional goal of the prototype system is to develop in-house expert system and knowledge engineering skills. The prototype system diagnoses antenna pointing and earth pointing problems that may occur within the TDRS Attitude Control System (ACS). Plans include expansion to fault isolation of problems in the most critical subsystems of the TDRS spacecraft. Long term benefits are anticipated with use of an expert system during future TDRS programs with increased mission support time, reduced problem solving time, and retained expert knowledge and experience. Phase 2 of the project is intended to provide NASA the necessary expertise and capability to define requirements, evaluate proposals, and monitor the development progress of a highly competent expert system for NASA's Tracking Data Relay Satellite. Phase 2 also envisions addressing two unexplored applications for expert systems, spacecraft integration and tests (I and T) and support to launch activities. The concept, goals, domain, tools, knowledge acquisition, developmental approach, and design of the expert system. It will explain how NASA obtained the knowledge and capability to develop the system in-house without assistance from outside consultants. Future plans will also be presented.

  19. Complexity of system-level fault diagnosis and diagnosability

    SciTech Connect

    Sullivan, G.F.

    1986-01-01

    It is now possible to design and build systems that incorporate a large number of processing elements. For this reason, fault-diagnosis at the system level, a research area pioneered by the work of Preparata, Metze, and Chien, is of increasing importance. The formalization of their model utilizes directed graphs together with labelings on edges and vertices. The two central problems introduced by the model are called the diagnosis and diagnosability problems. In the diagnosis problem, an algorithm must identify the faulty units of a system based on test results. In the diagnosability problem, an algorithm must determine the maximum number of faulty units a system can contain and still be guaranteed capable of successfully testing itself. One of the main open questions is resolved for this model by presenting the first polynomial time algorithm for the diagnosability problem. The solution uses network-flow techniques and runs in O(absolute value E absolute value V/sup 3/2/) time. Also presented is a new time-complexity bound of O(min(t absolute value E, t/sup 3/ + absolute value E)) for the diagnosis problem, where t is the maximum number of faulty units.

  20. Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies

    PubMed Central

    Krismer, Florian; Jellinger, Kurt A.; Scholz, Sonja W.; Seppi, Klaus; Stefanova, Nadia; Antonini, Angelo; Poewe, Werner; Wenning, Gregor K.

    2014-01-01

    There is evidence that the α-synucleinopathies Parkinson's disease (PD) and the Parkinson variant of multiple system atrophy (MSA-P) overlap at multiple levels. Both disorders are characterized by deposition of abnormally phosphorylated fibrillar α-synuclein within the central nervous system suggesting shared pathophysiological mechanisms. Despite the considerable clinical overlap in the early disease stages, MSA-P, in contrast to PD, is fatal and rapidly progressive. Moreover recent clinical studies have shown that surrogate markers of disease progression can be quantified easily and may reliably depict the rapid course of MSA. We therefore posit that, MSA-P may be exploited as a filter barrier in the development of disease-modifying therapeutic strategies targeting common pathophysiological mechanisms of α-synucleinopathies. This approach might reduce the number of negative phase III clinical trials, and, in turn, shift the available resources to earlier development stages, thereby increasing the number of candidate compounds validated. PMID:24894118

  1. Brain stem auditory evoked potentials in patients with multiple system atrophy with progressive autonomic failure (Shy-Drager syndrome).

    PubMed Central

    Prasher, D; Bannister, R

    1986-01-01

    Brain stem potentials from three groups of patients, namely those with pure progressive autonomic failure, Parkinson's disease and multisystem atrophy with progressive autonomic failure (Shy-Drager syndrome) were compared with each other and a group of normal subjects. In virtually all the patients with multisystem atrophy with progressive autonomic failure the brain stem potentials were abnormal in contrast to normal findings with Parkinson's disease. The closely associated group of patients with progressive autonomic failure alone also revealed no abnormalities of the BAEP. This separation of the two groups, Parkinson's disease and progressive autonomic failure from multisystem atrophy with progressive autonomic failure is important clinically as multiple system atrophy of the Shy-Drager type has extra-pyramidal features closely resembling Parkinsonism or a late onset cerebellar degeneration. From the abnormalities of the brain stem response in multisystem atrophy with progressive autonomic failure, it is clear that some disruption of the auditory pathway occurs in the ponto-medullary region as in nearly all patients there is a significant delay or reduction in the amplitude of components of the response generated beyond this region. The most likely area involved is the superior olivary complex. Images PMID:3958741

  2. Diagnosing battery behavior with an expert system in PROLOG

    NASA Technical Reports Server (NTRS)

    Kirkwood, N.; Weeks, D. J.

    1986-01-01

    Power for the Hubble Space Telescope comes from a system of 20 solar panel assemblies (SPAs) and six nickel-cadmium batteries. The HST battery system is simulated by the HST Electrical Power System (EPS) testbed at Marshall Space Flight Center. The Nickel Cadmium Battery Expert System (NICBES) is being used to diagnose faults of the testbed system, evaluate battery status and provide decision support for the engineer. Extensive telemetry of system operating conditions is relayed through a DEC LSI-11. A BASIC program running on a PC monitors the flow of data, figures cell divergence and recharge ratio, and stores these values, along with other selected data, for use by the expert system.

  3. Development of Intelligent Suits for Disuse Atrophy of Musculoskeletal System Using Hybrid Exercise Method

    NASA Astrophysics Data System (ADS)

    Shiba, Naoto; Yoshimitsu, Kazuhiro; Matsugaki, Tohru; Narita, Arata; Maeda, Takashi; Inada, Tomohisa; Tagawa, Yoshihiko; Numada, Kiyoshi; Nishi, Tetsuya

    We developed ‘Hybrid exercise’ method that was designed to maintain the musculoskeletal system by using electrically stimulated antagonist muscles to resist volitional contraction of agonist muscles. This approach also produces a minimum of inertial reaction forces and has the advantage that it may minimize the need for external stabilization that is currently necessary during exercise in a weightlessness environment. The purpose of this study was to develop the intelligent suits with virtual reality (VR) system that had function of preventing disuse atrophy of musculoskeletal system using hybrid exercise system. Installing of the hybrid exercise system to the subject became easy by the intelligent suits. VR system realized the sense of sight by computer graphics animation synchronized with subjects' motion, and sense of force induced by electrical stimulation. By using VR system, the management of the exercise accomplishment degree was enabled easily because the device could record the exercise history. Intelligent suits with VR hybrid exercise system might become one of the useful countermeasures for the disuse musculoskeletal system in the space.

  4. The Neuropsychology (Broadly Conceived) of Multiple System Atrophy, Progressive Supranuclear Palsy, and Corticobasal Degeneration.

    PubMed

    Gerstenecker, Adam

    2017-09-15

    To review the cognitive and behavioral features of the different atypical parkinsonian syndromes in which motor symptoms dominate early clinical symptomology: multiple systems atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). The impact of cognitive and behavioral deficits on quality of life, associations between neuropsychological and neuropsychiatric findings and brain imaging, and cognitive and behavioral symptom management are also discussed. A review of the available MSA, PSP, and CBD literature was conducted, with emphasis given to studies investigating the cognitive and behavioral features of the syndromes. Although the three reviewed atypical parkinsonian syndromes share many similarities to each other and PD from a neuropsychological perspective, differences in prevalence and severity of cognitive impairment and patterns of performance on neuropsychological and neuropsychiatric measures exist in the research literature. Cognitive and behavioral features are early and pervasive aspects of MSA, PSP, and CBD.

  5. Parkinson’s disease with Onuf’s nucleus involvement mimicking multiple system atrophy

    PubMed Central

    O’Sullivan, Sean Stephen; Massey, Luke A; Williams, David R; Revesz, Tamas; Lees, Andrew; Holton, Janice

    2009-01-01

    Urinary frequency, urgency and nocturia are common complaints in Parkinson’s disease (PD). The hypothesis most widely proposed to explain neurogenic bladder symptoms in PD is that cell loss in the substantia nigra may cause detrusor hyperactivity due to a loss in the D1 receptor-mediated tonic inhibition of the micturition reflex, although other causes including anti-parkinsonian medication cortical effects have been considered.1 We present the clinical and pathological findings of a patient with parkinsonism who presented with prominent dysautonomia and a poor response to dopaminergic medications and was considered to have possible multiple system atrophy parkinsonism (MSA-P). Pathological examination revealed that the patient had PD with α-synuclein pathology in the Onuf’s nucleus (ON). PMID:21686637

  6. Unusual compulsive behaviors primarily related to dopamine agonist therapy in Parkinson's disease and multiple system atrophy.

    PubMed

    McKeon, Andrew; Josephs, Keith A; Klos, Kevin J; Hecksel, Kathleen; Bower, James H; Michael Bostwick, J; Eric Ahlskog, J

    2007-12-01

    Unusual compulsive behaviors (weighing, card and video game playing, fishing, gardening, intense interest in established hobbies, locking and unlocking doors, repetitive dressing and undressing) occurred in relation to dopamine agonist therapy (six patients) and levodopa therapy (one patient) in seven patients with parkinsonism (seven Parkinson's disease, one multiple system atrophy). These behaviors occurred in tandem with pathological gambling, hypersexuality, compulsive eating, compulsive shopping or punding in six of the seven cases. Obsessive thoughts were present in one patient, with no prior history of obsessive-compulsive disorder. The simultaneous occurrence of these phenomenologically distinct behaviors in this group of patients suggests that a broad spectrum of psychopathology may occur in this context and should be monitored for in routine neurological practice.

  7. Cognition in a multiple system atrophy series of cases from Argentina.

    PubMed

    Gatto, Emilia; Demey, Ignacio; Sanguinetti, Ana; Parisi, Virginia; Etcheverry, José Luis; Rojas, Galeno; Wenning, Gregor K

    2014-10-01

    Cognitive dysfunction may occur in 17-40% of patients with multiple system atrophy (MSA). It has been suggested a milder cognitive impairment in cerebellar (MSA-C) than in parkinsonian variant (MSA-P). However, differences in cognitive profiles remain under discussion. To evaluate cognitive features in a series of patients with "probable MSA" from Argentina. After informed consent was obtained, an extensive cognitive tests battery was administered. Nine patients (6 MSA-P and 3 MSA-C) composed the sample. Depression was detected in 43% of patients. Seven patients showed at least one cognitive domain impairment. Temporospatial orientation, visuospatial abilities, executive and attentional functions, episodic memory and language were compromised in MSA-P, while MSA-C dysfunction was restricted to attentional and executive domains. Despite the small sample size, our findings could suggest a more widespread cognitive impairment in MSA-P than MSA-C.

  8. Mutational analysis of parkin and PINK1 in multiple system atrophy

    PubMed Central

    Brooks, Janet A.; Houlden, Henry; Melchers, Anna; Islam, Ansha J.; Ding, Jinhui; Li, Abi; Paudel, Reema; Revesz, Tamas; Holton, Janice L.; Wood, Nick; Lees, Andrew; Singleton, Andrew B.; Scholz, Sonja W.

    2009-01-01

    Multiple system atrophy (MSA) and Parkinson’s disease (PD) are progressive neurodegenerative disorders with overlapping clinical, biochemical and genetic features. To test the hypothesis that the Parkinson’s disease genes parkin and PINK1 also play a role in the pathogenesis of MSA, we performed a mutational screening study involving 87 pathology-proven MSA cases. In parkin we identified eight sequence variants and four heterozygous deletions, and in PINK1 we identified nine variants of which two silent mutations have not been previously reported (p.Gly189Gly and p.Arg337Arg). The frequencies of the observed variants were not significantly different from previously published control data and none of the possibly pathogenic variants were found in a homozygous state. Our results indicate that genetic variants at the parkin and PINK1 loci do not play a critical role in the pathogenesis of MSA. PMID:20034704

  9. [Towards more efficient clinical trials for multiple system atrophy in Japan].

    PubMed

    Ichikawa, Yaeko

    2012-10-01

    Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder characterized by various combinations of autonomic dysfunction, cerebellar symptoms, parkinsonism, and pyramidal signs. Although MSA is known as a sporadic disease, multiplex families with MSA suggest a genetic predisposition to MSA. The advanced genome research using high-throughput sequencing technology will enable identification of MSA-related genes. Disease-modifying therapy for MSA is expected to be available in the near future. In 2003, the Japan MSA research consortium (JAMSAC) was established to understand the natural history of MSA, which could be the basis for designing clinical trials, and to elucidate the molecular pathogenetic mechanisms of MSA. In Japan, MSA with predominant cerebellar ataxia (MSA-C) is more frequent than that MSA with predominant parkinsonism (MSA-P); this is in contrast to the previous reports from Europe and North America. JAMSAC has conducted a prospective study on the natural history of MSA by using the established consensus criteria for MSA and the unified multiple system atrophy rating scale (UMSARS). Determining the optimum endpoint, sample size, and duration of trial is essential for designing efficient clinical trials. In addition, more sensitive diagnostic criteria are needed to recruit MSA patients in the earlier phase of the condition. Sample size estimation from a longitudinal study suggested the need for sensitive outcome measures, other than UMSARS. Although the knowledge on MSA has increased in the past several decades, biomarkers for this disease are not yet available. The establishment of more sensitive diagnostic criteria and the development of biomarkers are required to conduct more efficient clinical trials for MSA.

  10. Simultaneous assessment of cognitive and affective functions in multiple system atrophy and cortical cerebellar atrophy in relation to computerized touch-panel screening tests.

    PubMed

    Kawahara, Yuko; Ikeda, Yoshio; Deguchi, Kentaro; Kurata, Tomoko; Hishikawa, Nozomi; Sato, Kota; Kono, Syoichiro; Yunoki, Taijun; Omote, Yoshio; Yamashita, Toru; Abe, Koji

    2015-04-15

    Cognitive impairment and affective dysfunction of multiple system atrophy (MSA) and cortical cerebellar atrophy (CCA) have not been simultaneously examined comparing standard test batteries and a sensitive tool to detect subtle cognitive decline in patients. In the present study, we simultaneously examined cognitive and affective ability in MSA with predominant cerebellar ataxia (MSA-C, n=25), MSA with predominant parkinsonism (MSA-P, n=8), and CCA (n=14) patients using computerized touch panel screening tests. Mini-mental state examination (MMSE), Hasegawa dementia scale-revised (HDS-R), frontal assessment battery (FAB), and Montreal cognitive assessment (MoCA) scores were significantly lower in MSA-C patients than in age-and gender-matched normal controls. One MSA-C patient showed a decrease in the regional cerebral blood flow (rCBF) of the frontal lobe. MSA-P patients showed no such cognitive decline. Only FAB and MoCA scores were significantly lower in the CCA patients. MSA and CCA patients also showed a mild to moderate depressive state. Touch-panel screening tests demonstrated a significant decline of beating devils game in all three disease groups including MSA-P patients, and a significant extension of the flipping cards game only in MSA-C patients. The present study demonstrated different cognitive and affective functions among MSA-C, MSA-P, and CCA patients, and a sensitive screening method for cognitive assessment using touch-panel tests. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. "Atypical" atypical parkinsonism: new genetic conditions presenting with features of progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy-a diagnostic guide.

    PubMed

    Stamelou, Maria; Quinn, Niall P; Bhatia, Kailash P

    2013-08-01

    Recently, a number of genetic parkinsonian conditions have been recognized that share some features with the clinical syndromes of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA), the classic phenotypic templates of atypical parkinsonism. For example, patients with progranulin, dynactin, or ATP13A gene mutations may have vertical supranuclear gaze palsy. This has made differential diagnosis difficult for practitioners. In this review, our goal is to make clinicians aware of these genetic disorders and provide clinical clues and syndromic associations, as well as investigative features, that may help in diagnosing these disorders. The correct identification of these patients has important clinical, therapeutic, and research implications. © 2013 Movement Disorder Society.

  12. Role of dysautonomic symptoms in distinguishing Parkinson's disease (PD) from multiple system atrophy (MSA-P) within a year of developing motor symptoms.

    PubMed

    Ragothaman, Mona; Swaminath, Pazhayannur V; Sarangmath, Nagaraja; Koshy, Suma; Adhyam, Mohan; Subbakrishna, Dodaballapur K; Mathias, Christopher J; Muthane, Uday B

    2011-02-01

    Can dysautonomic symptoms occurring within a year of developing motor symptoms distinguish Multiple system atrophy-Parkinsonian (MSA-P) from Parkinson's disease (PD)? Seventy-two Parkinsonian patients diagnosed as probable PD or MSA-P. PD (n = 58, 80.6%) and MSA (n = 14, 19.4%) patients were of similar age and had motor symptoms for similar duration. PD first presents with motor symptoms (68.3%) while MSA-P presents with dysautonomia (85.7%). Urinary incontinence was reported by MSA-P (64%) at their first visit and was absent in most PD (98%) patients. Urinary incontinence and orthostatic symptoms occurring in a parkinsonian patient within one-year history of motor symptoms suggests a diagnosis of MSA-P with high accuracy and their absence suggests PD.

  13. Chemotherapy in newly diagnosed primary central nervous system lymphoma

    PubMed Central

    Hashemi-Sadraei, Nooshin; Peereboom, David M.

    2010-01-01

    Primary central nervous system lymphoma (PCNSL) accounts for only 3% of brain tumors. It can involve the brain parenchyma, leptomeninges, eyes and the spinal cord. Unlike systemic lymphoma, durable remissions remain uncommon. Although phase III trials in this rare disease are difficult to perform, many phase II trials have attempted to define standards of care. Treatment modalities for patients with newly diagnosed PCNSL include radiation and/or chemotherapy. While the role of radiation therapy for initial management of PCNSL is controversial, clinical trials will attempt to improve the therapeutic index of this modality. Routes of chemotherapy administration include intravenous, intraocular, intraventricular or intra-arterial. Multiple trials have outlined different methotrexate-based chemotherapy regimens and have used local techniques to improve drug delivery. A major challenge in the management of patients with PCNSL remains the delivery of aggressive treatment with preservation of neurocognitive function. Because PCNSL is rare, it is important to perform multicenter clinical trials and to incorporate detailed measurements of long-term toxicities. In this review we focus on different chemotherapeutic approaches for immunocompetent patients with newly diagnosed PCNSL and discuss the role of local drug delivery in addition to systemic therapy. We also address the neurocognitive toxicity of treatment. PMID:21789140

  14. Diagnosing delivery problems in the White House Information Distribution System

    SciTech Connect

    Nahabedian, M.; Shrobe, H.

    1996-12-31

    As part of a collaboration with the White House Office of Media Affairs, members of the MIT Artificial Intelligence Laboratory designed a system, called COMLINK, which distributes a daily stream of documents released by the Office of Media Affairs. Approximately 4000 direct subscribers receive information from this service but more than 100,000 people receive the information through redistribution channels. The information is distributed via Email and the World Wide Web. In such a large scale distribution scheme, there is a constant problem of subscriptions becoming invalid because the user`s Email account has terminated. This causes a backwash of hundreds of {open_quotes}bounced mail{close_quotes} messages per day which must be processed by the operators of the COMLINK system. To manage this annoying but necessary task, an expert system named BMES was developed to diagnose the failures of information delivery.

  15. Pharmacodynamics of a low subacute levodopa dose helps distinguish between multiple system atrophy with predominant Parkinsonism and Parkinson's disease.

    PubMed

    Calandra-Buonaura, Giovanna; Doria, Andrea; Lopane, Giovanna; Guaraldi, Pietro; Capellari, Sabina; Martinelli, Paolo; Cortelli, Pietro; Contin, Manuela

    2016-02-01

    The differential diagnosis between multiple system atrophy with predominant parkinsonism (MSA-P) and Parkinson's disease (PD) may be challenging at disease onset. Levodopa responsiveness helps distinguish the two groups, but studies evaluating this issue using objective standardized tests are scanty. We retrospectively examined the extent of levodopa response by an objective kinetic-dynamic test in a series of patients prospectively followed up for a parkinsonian syndrome and eventually diagnosed as MSA-P or PD. Sixteen MSA-P and 31 PD patients under chronic levodopa therapy received a first morning fasting dose of levodopa/benserazide (100/25 mg) or levodopa/carbidopa (125/12.5 or 100/25 mg) and underwent simultaneous serial assessments of plasma levodopa concentration and alternate finger tapping frequency up to 3 h post dosing. The main levodopa pharmacodynamic variables were the maximum percentage increase in tapping frequency over baseline values (ΔTapmax %) and the area under the tapping effect-time curve (AUCTap). Levodopa pharmacokinetics did not show significant differences between MSA-P and PD, whereas both the magnitude and overall extent of levodopa tapping effect were markedly reduced in the MSA-P group (p < 0.001). The combined use of specific cut-off values for both the main pharmacodynamic variables, ΔTapmax % <20% and AUCTap <1900 [(tapping/min)·min], correctly discriminated 15 out of 16 MSA-P patients from PD patients. A combined estimation of these pharmacodynamic variables after a subacute low levodopa dose may be a simple and practical clinical tool to aid the differential diagnosis between MSA-P and PD.

  16. The TWEAK–Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy in mice

    PubMed Central

    Mittal, Ashwani; Bhatnagar, Shephali; Kumar, Akhilesh; Lach-Trifilieff, Estelle; Wauters, Sandrine; Li, Hong; Makonchuk, Denys Y.; Glass, David J.

    2010-01-01

    Skeletal muscle atrophy occurs in a variety of clinical settings, including cachexia, disuse, and denervation. Inflammatory cytokines have been shown to be mediators of cancer cachexia; however, the role of cytokines in denervation- and immobilization-induced skeletal muscle loss remains unknown. In this study, we demonstrate that a single cytokine, TNF-like weak inducer of apoptosis (TWEAK), mediates skeletal muscle atrophy that occurs under denervation conditions. Transgenic expression of TWEAK induces atrophy, fibrosis, fiber-type switching, and the degradation of muscle proteins. Importantly, genetic ablation of TWEAK decreases the loss of muscle proteins and spared fiber cross-sectional area, muscle mass, and strength after denervation. Expression of the TWEAK receptor Fn14 (fibroblast growth factor–inducible receptor 14) and not the cytokine is significantly increased in muscle upon denervation, demonstrating an unexpected inside-out signaling pathway; the receptor up-regulation allows for TWEAK activation of nuclear factor κB, causing an increase in the expression of the E3 ubiquitin ligase MuRF1. This study reveals a novel mediator of skeletal muscle atrophy and indicates that the TWEAK–Fn14 system is an important target for preventing skeletal muscle wasting. PMID:20308426

  17. The TWEAK-Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy in mice.

    PubMed

    Mittal, Ashwani; Bhatnagar, Shephali; Kumar, Akhilesh; Lach-Trifilieff, Estelle; Wauters, Sandrine; Li, Hong; Makonchuk, Denys Y; Glass, David J; Kumar, Ashok

    2010-03-22

    Skeletal muscle atrophy occurs in a variety of clinical settings, including cachexia, disuse, and denervation. Inflammatory cytokines have been shown to be mediators of cancer cachexia; however, the role of cytokines in denervation- and immobilization-induced skeletal muscle loss remains unknown. In this study, we demonstrate that a single cytokine, TNF-like weak inducer of apoptosis (TWEAK), mediates skeletal muscle atrophy that occurs under denervation conditions. Transgenic expression of TWEAK induces atrophy, fibrosis, fiber-type switching, and the degradation of muscle proteins. Importantly, genetic ablation of TWEAK decreases the loss of muscle proteins and spared fiber cross-sectional area, muscle mass, and strength after denervation. Expression of the TWEAK receptor Fn14 (fibroblast growth factor-inducible receptor 14) and not the cytokine is significantly increased in muscle upon denervation, demonstrating an unexpected inside-out signaling pathway; the receptor up-regulation allows for TWEAK activation of nuclear factor kappaB, causing an increase in the expression of the E3 ubiquitin ligase MuRF1. This study reveals a novel mediator of skeletal muscle atrophy and indicates that the TWEAK-Fn14 system is an important target for preventing skeletal muscle wasting.

  18. Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy

    PubMed Central

    Powis, Rachael A.; Karyka, Evangelia; Boyd, Penelope; Côme, Julien; Jones, Ross A.; Zheng, Yinan; Szunyogova, Eva; Groen, Ewout J.N.; Hunter, Gillian; Thomson, Derek; Wishart, Thomas M.; Becker, Catherina G.; Parson, Simon H.; Martinat, Cécile; Azzouz, Mimoun; Gillingwater, Thomas H.

    2016-01-01

    The autosomal recessive neuromuscular disease spinal muscular atrophy (SMA) is caused by loss of survival motor neuron (SMN) protein. Molecular pathways that are disrupted downstream of SMN therefore represent potentially attractive therapeutic targets for SMA. Here, we demonstrate that therapeutic targeting of ubiquitin pathways disrupted as a consequence of SMN depletion, by increasing levels of one key ubiquitination enzyme (ubiquitin-like modifier activating enzyme 1 [UBA1]), represents a viable approach for treating SMA. Loss of UBA1 was a conserved response across mouse and zebrafish models of SMA as well as in patient induced pluripotent stem cell–derive motor neurons. Restoration of UBA1 was sufficient to rescue motor axon pathology and restore motor performance in SMA zebrafish. Adeno-associated virus serotype 9–UBA1 (AAV9-UBA1) gene therapy delivered systemic increases in UBA1 protein levels that were well tolerated over a prolonged period in healthy control mice. Systemic restoration of UBA1 in SMA mice ameliorated weight loss, increased survival and motor performance, and improved neuromuscular and organ pathology. AAV9-UBA1 therapy was also sufficient to reverse the widespread molecular perturbations in ubiquitin homeostasis that occur during SMA. We conclude that UBA1 represents a safe and effective therapeutic target for the treatment of both neuromuscular and systemic aspects of SMA. PMID:27699224

  19. A novel approach to modeling and diagnosing the cardiovascular system

    SciTech Connect

    Keller, P.E.; Kangas, L.J.; Hashem, S.; Kouzes, R.T.; Allen, P.A.

    1995-07-01

    A novel approach to modeling and diagnosing the cardiovascular system is introduced. A model exhibits a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. Potentially, a model will be incorporated into a cardiovascular diagnostic system. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and the variables of an individual at a given time are used for diagnosis. This approach also exploits sensor fusion to optimize the utilization of biomedical sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.

  20. Diagnosing Hybrid Systems: a Bayesian Model Selection Approach

    NASA Technical Reports Server (NTRS)

    McIlraith, Sheila A.

    2005-01-01

    In this paper we examine the problem of monitoring and diagnosing noisy complex dynamical systems that are modeled as hybrid systems-models of continuous behavior, interleaved by discrete transitions. In particular, we examine continuous systems with embedded supervisory controllers that experience abrupt, partial or full failure of component devices. Building on our previous work in this area (MBCG99;MBCG00), our specific focus in this paper ins on the mathematical formulation of the hybrid monitoring and diagnosis task as a Bayesian model tracking algorithm. The nonlinear dynamics of many hybrid systems present challenges to probabilistic tracking. Further, probabilistic tracking of a system for the purposes of diagnosis is problematic because the models of the system corresponding to failure modes are numerous and generally very unlikely. To focus tracking on these unlikely models and to reduce the number of potential models under consideration, we exploit logic-based techniques for qualitative model-based diagnosis to conjecture a limited initial set of consistent candidate models. In this paper we discuss alternative tracking techniques that are relevant to different classes of hybrid systems, focusing specifically on a method for tracking multiple models of nonlinear behavior simultaneously using factored sampling and conditional density propagation. To illustrate and motivate the approach described in this paper we examine the problem of monitoring and diganosing NASA's Sprint AERCam, a small spherical robotic camera unit with 12 thrusters that enable both linear and rotational motion.

  1. Multiple system atrophy presenting as parkinsonism: clinical features and diagnostic criteria.

    PubMed Central

    Albanese, A; Colosimo, C; Bentivoglio, A R; Fenici, R; Melillo, G; Colosimo, C; Tonali, P

    1995-01-01

    To evaluate the possibility that parkinsonian signs may be the only presenting feature of multiple system atrophy (MSA), parkinsonian patients were studied who had no atypical clinical signs and had no symptoms of autonomic dysfunction, but who reported that they had not experienced the anticipated good response to dopaminergic treatment. These stringent criteria identified 20 patients from a series of 298 consecutive parkinsonian outpatients. The following clinical pointers were analysed: (a) rate of disease progression; (b) symmetry of parkinsonian symptoms and signs; (c) occurrence of resting tremor during the first three years from onset. In addition, all patients underwent (d) acute and chronic challenge with dopaminergic drugs; (e) cardiovascular reflex autonomic function tests; (f) high field MRI. Rapid progression of disease was seen in 45% of patients, onset was symmetric in 25%, tremor was absent at onset in 70%, response to dopaminergic drug challenges was inadequate in 40%, abnormal cardiovascular reflexes occurred in 50%, and some abnormal MRI finding occurred in 35% of cases. Each of these features was equally weighted by giving to each patient a 0 to 6 point score corresponding to the number of abnormal findings. Fifteen patients scoring higher than 1 were considered at risk for having MSA: five of them were classified as clinically possible (score 2), six as clinically probable (score 3-4), and four patients were classified as clinically definite multiple system atrophy (score 5). The six pointers considered were variably combined in each patient, none of them being universally abnormal in patients with high scores. The patients were followed up for a mean 2.1 (SEM 0.65) years. All but one of the 10 patients prospectively classified as probable or definite MSA developed unequivocal clinical signs of fully symptomatic MSA. A receiver operator characteristic cure was plotted for the prospective score based on follow up diagnosis. The best compromise

  2. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy

    PubMed Central

    Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F.; Bowerman, Melissa; Meijboom, Katharina E.; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J.; Wood, Matthew J. A.

    2016-01-01

    The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA. PMID:27621445

  3. An autopsy case of preclinical multiple system atrophy (MSA-C).

    PubMed

    Kon, Tomoya; Mori, Fumiaki; Tanji, Kunikazu; Miki, Yasuo; Wakabayashi, Koichi

    2013-12-01

    Multiple system atrophy (MSA) is divided into two clinical subtypes: MSA with predominant parkinsonian features (MSA-P) and MSA with predominant cerebellar dysfunction (MSA-C). We report a 71-year-old Japanese man without clinical signs of MSA, in whom post mortem examination revealed only slight gliosis in the pontine base and widespread occurrence of glial cytoplasmic inclusions in the central nervous system, with the greatest abundance in the pontine base and cerebellar white matter. Neuronal cytoplasmic inclusions (NCIs) and neuronal nuclear inclusions (NNIs) were almost restricted to the pontine and inferior olivary nuclei. It was noteworthy that most NCIs were located in the perinuclear area, and the majority of NNIs were observed adjacent to the inner surface of the nuclear membrane. To our knowledge, only four autopsy cases of preclinical MSA have been reported previously, in which neuronal loss was almost entirely restricted to the substantia nigra and/or putamen. Therefore, the present autopsy case of preclinical MSA-C is considered to be the first of its kind to have been reported. The histopathological features observed in preclinical MSA may represent the early pattern of MSA pathology.

  4. Overexpression of the alpha1B-adrenergic receptor causes apoptotic neurodegeneration: multiple system atrophy.

    PubMed

    Zuscik, M J; Sands, S; Ross, S A; Waugh, D J; Gaivin, R J; Morilak, D; Perez, D M

    2000-12-01

    Progress toward elucidating the function of alpha1B-adrenergic receptors (alpha1BARs) in the central nervous system has been constrained by a lack of agonists and antagonists with adequate alpha1B-specificity. We have obviated this constraint by generating transgenic mice engineered to overexpress either wild-type or constitutively active alpha1BARs in tissues that normally express the receptor, including the brain. All transgenic lines showed granulovacular neurodegeneration, beginning in alpha1B-expressing domains of the brain and progressing with age to encompass all areas. The degeneration was apoptotic and did not occur in non-transgenic mice. Correspondingly, transgenic mice showed an age-progressive hindlimb disorder that was parkinsonian-like, as demonstrated by rescue of the dysfunction by 3, 4-dihydroxyphenylalanine and considerable dopaminergic-neuronal degeneration in the substantia nigra. Transgenic mice also had a grand mal seizure disorder accompanied by a corresponding dysplasia and neurodegeneration of the cerebral cortex. Both behavioral phenotypes (locomotor impairment and seizure) could be partially rescued with the alpha1AR antagonist terazosin, indicating that alpha1AR signaling participated directly in the pathology. Our results indicate that overstimulation of alpha1BAR leads to apoptotic neurodegeneration with a corresponding multiple system atrophy indicative of Shy-Drager syndrome, a disease whose etiology is unknown.

  5. Central hemodynamics and arterial stiffness in idiopathic and multiple system atrophy.

    PubMed

    Franzen, Klaas; Fliegen, Sabine; Koester, Jelena; Martin, Rafael Campos; Deuschl, Günther; Reppel, Michael; Mortensen, Kai; Schneider, Susanne A

    2017-02-01

    Blood pressure is commonly abnormal in parkinsonian disorders, but central hemodynamics and arterial stiffness, well-established predictors of total cardiovascular risk, have rarely been studied in these disorders. 32 patients [27 with idiopathic Parkinson's disease (iPD); 5 with multiple system atrophy (MSA)] and 15 controls matched for cardiac risk factors underwent 24 h-ambulatory blood pressure recordings using an I.E.M. device (Mobil-O-Graph™), measuring peripheral pressure and calculating central pressures and arterial stiffness. Mean augmentation indices corrected for heart rate (AIx@75) were significantly lower and pulse wave velocities were significantly elevated in patients compared to controls. Central systolic blood pressure, cardiac output and daytime total vascular resistance were significantly elevated in patients. Mean nocturnal systolic peripheral blood pressure and nocturnal heart rates were also significantly higher; 56.3% of patients had nocturnal hypertension (80% of the MSA group); 85.2% showed non-dipping. This supports previous findings of reduced vulnerability to systemic atherosclerosis and end-organ damage in treated PD. Yet, hemodynamic abnormalities were common and often remained asymptomatic.

  6. An expert system for diagnosing environmentally induced spacecraft anomalies

    NASA Technical Reports Server (NTRS)

    Rolincik, Mark; Lauriente, Michael; Koons, Harry C.; Gorney, David

    1992-01-01

    A new rule-based, machine independent analytical tool was designed for diagnosing spacecraft anomalies using an expert system. Expert systems provide an effective method for saving knowledge, allow computers to sift through large amounts of data pinpointing significant parts, and most importantly, use heuristics in addition to algorithms, which allow approximate reasoning and inference and the ability to attack problems not rigidly defined. The knowledge base consists of over two-hundred (200) rules and provides links to historical and environmental databases. The environmental causes considered are bulk charging, single event upsets (SEU), surface charging, and total radiation dose. The system's driver translates forward chaining rules into a backward chaining sequence, prompting the user for information pertinent to the causes considered. The use of heuristics frees the user from searching through large amounts of irrelevant information and allows the user to input partial information (varying degrees of confidence in an answer) or 'unknown' to any question. The modularity of the expert system allows for easy updates and modifications. It not only provides scientists with needed risk analysis and confidence not found in algorithmic programs, but is also an effective learning tool, and the window implementation makes it very easy to use. The system currently runs on a Micro VAX II at Goddard Space Flight Center (GSFC). The inference engine used is NASA's C Language Integrated Production System (CLIPS).

  7. System and method for diagnosing EGR performance using NOx sensor

    DOEpatents

    Mazur, Christopher John

    2003-12-23

    A method and system for diagnosing a condition of an EGR valve used in an engine system. The EGR valve controls the portion exhaust gases produced by such engine system and fed back to an intake of such engine system. The engine system includes a NOx sensor for measuring NOx in such exhaust. The method includes: determining a time rate of change in NOx measured by the NOx sensor; comparing the determined time rate of change in the measured NOx with a predetermined expected time rate of change in measured NOx; and determining the condition of the EGR valve as a function of such comparison. The method also includes: determining from NOx measured by the NOx sensor and engine operating conditions indications of instances when samples of such measured NOx are greater than an expected maximum NOx level for such engine condition and less than an expected minimum NOx level for such engine condition; and determining the condition of the EGR valve as a function of a statistical analysis of such indications. The method includes determining whether the NOx sensor is faulty and wherein the EGR condition determining includes determining whether the NOx sensor is faulty.

  8. Abnormal cardiac [(123)I]-meta-iodobenzylguanidine uptake in multiple system atrophy.

    PubMed

    Nagayama, Hiroshi; Ueda, Masayuki; Yamazaki, Mineo; Nishiyama, Yasuhiro; Hamamoto, Makoto; Katayama, Yasuo

    2010-08-15

    [(123)I]-Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is useful for distinguishing multiple system atrophy (MSA) from Parkinson disease. In this study, longitudinal observation using MIBG myocardial scintigraphy was carried out in patients with MSA to evaluate the association of myocardial MIBG uptake with clinical features. A total of 96 MIBG examinations were performed in 52 patients with MSA. The heart/mediastinum (H/M) ratio of MIBG uptake at 240 minutes after injection was below the lower limit in 16 patients with MSA (31.3%). Overall, the H/M ratio correlated with neither disease duration nor severity. In the follow-up observations, the H/M ratio did not show any specific trends, in contrast with the continuous decrease observed in patients with Parkinson's disease. This data clearly showed that cardiac MIBG uptake cannot necessarily be preserved in patients with MSA and that approximately 30% of patients with MSA showed decreased MIBG uptake without any correlation to disease duration or severity.

  9. Prediction of orthostatic hypotension in multiple system atrophy and Parkinson disease

    PubMed Central

    Sun, Zhanfang; Jia, Dandan; Shi, Yuting; Hou, Xuan; Yang, Xiaosu; Guo, Jifeng; Li, Nan; Wang, Junling; Sun, Qiying; Zhang, Hainan; Lei, Lifang; Shen, Lu; Yan, Xinxiang; Xia, Kun; Jiang, Hong; Tang, Beisha

    2016-01-01

    Orthostatic hypotension (OH) is common in multiple system atrophy (MSA) and Parkinson disease (PD), generally assessed through a lying-to-standing orthostatic test. However, standing blood pressure may not be available due to orthostatic intolerance or immobilization for such patients. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were successively measured in supine, sitting, and standing positions in patients with MSA and PD. Receiver operating characteristic analysis was used to evaluate diagnostic performance of the drops of sitting SBP or DBP. OH and severe OH were respectively regarded as “gold standard”. The drops of SBP in standing position were associated with increased disease severity for MSA and correlated with age for PD. In MSA group, drops in sitting SBP ≥ 14 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH, and drops in sitting SBP ≥ 18 mmHg or DBP ≥ 8 mmHg for severe OH. In PD group, drops in sitting SBP ≥ 10 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH. The lying-to-sitting orthostatic test is an alternative method for detection of OH in MSA and PD, especially when standing BP could not be validly measured due to various reasons. PMID:26867507

  10. Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure

    NASA Technical Reports Server (NTRS)

    Benarroch, E. E.; Smithson, I. L.; Low, P. A.; Parisi, J. E.

    1998-01-01

    The ventrolateral portion of the intermediate reticular formation of the medulla (ventrolateral medulla, VLM), including the C1/A1 groups of catecholaminergic neurons, is thought to be involved in control of sympathetic cardiovascular outflow, cardiorespiratory interactions, and reflex control of vasopressin release. As all these functions are affected in patients with multiple systems atrophy (MSA) with autonomic failure, we sought to test the hypothesis that catecholaminergic (tyrosine hydroxylase [TH]-positive) neurons of the VLM are depleted in these patients. Medullas were obtained at autopsy from 4 patients with MSA with prominent autonomic failure and 5 patients with no neurological disease. Patients with MSA had laboratory evidence of severe adrenergic sudomotor and cardiovagal failure. Tissue was immersion fixed in 2% paraformaldehyde at 4 degrees C for 24 hours and cut into 1-cm blocks in the coronal plane from throughout the medulla. Serial 50-microm sections were collected and one section every 300 microm was stained for TH. There was a pronounced depletion of TH neurons in the rostral VLM in all cases of MSA. There was also significant reduction of TH neurons in the caudal VLM in 3 MSA patients compared with 3 control subjects. In 2 MSA cases and in 2 control subjects, the thoracic spinal cord was available for study. There was also depletion of TH fibers and sympathetic preganglionic neurons (SPNs) in the 2 MSA cases examined. Thus, depletion of catecholaminergic neurons in the VLM may provide a substrate for some of the autonomic and endocrine manifestations of MSA.

  11. Fluid biomarkers in multiple system atrophy: A review of the MSA Biomarker Initiative.

    PubMed

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy; Gerhard, Alexander; Jellinger, Kurt; Jeromin, Andreas; Krismer, Florian; Mollenhauer, Brit; Schlossmacher, Michael G; Shaw, Leslie M; Verbeek, Marcel M; Wenning, Gregor K; Winge, Kristian; Zhang, Jing; Meissner, Wassilios G

    2015-08-01

    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results suggest that combining several CSF fluid biomarkers may be more successful than using single markers, at least for the diagnosis. Currently, the clinically most useful markers may comprise a combination of the light chain of neurofilament (which is consistently elevated in MSA compared to controls and Parkinson's disease), metabolites of the catecholamine pathway and proteins such as α-synuclein, DJ-1 and total-tau. Beyond future efforts in biomarker discovery, the harmonization of standard operating procedures will be crucial for future success.

  12. Speech disorders reflect differing pathophysiology in Parkinson's disease, progressive supranuclear palsy and multiple system atrophy.

    PubMed

    Rusz, Jan; Bonnet, Cecilia; Klempíř, Jiří; Tykalová, Tereza; Baborová, Eva; Novotný, Michal; Rulseh, Aaron; Růžička, Evžen

    2015-01-01

    Although speech disorder is frequently an early and prominent clinical feature of Parkinson's disease (PD) as well as atypical parkinsonian syndromes (APS) such as progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), there is a lack of objective and quantitative evidence to verify whether any specific speech characteristics allow differentiation between PD, PSP and MSA. Speech samples were acquired from 77 subjects including 15 PD, 12 PSP, 13 MSA and 37 healthy controls. The accurate differential diagnosis of dysarthria subtypes was based on the quantitative acoustic analysis of 16 speech dimensions. Dysarthria was uniformly present in all parkinsonian patients but was more severe in PSP and MSA than in PD. Whilst PD speakers manifested pure hypokinetic dysarthria, ataxic components were more affected in MSA whilst PSP subjects demonstrated severe deficits in hypokinetic and spastic elements of dysarthria. Dysarthria in PSP was dominated by increased dysfluency, decreased slow rate, inappropriate silences, deficits in vowel articulation and harsh voice quality whereas MSA by pitch fluctuations, excess intensity variations, prolonged phonemes, vocal tremor and strained-strangled voice quality. Objective speech measurements were able to discriminate between APS and PD with 95% accuracy and between PSP and MSA with 75% accuracy. Dysarthria severity in APS was related to overall disease severity (r = 0.54, p = 0.006). Dysarthria with various combinations of hypokinetic, spastic and ataxic components reflects differing pathophysiology in PD, PSP and MSA. Thus, motor speech examination may provide useful information in the evaluation of these diseases with similar manifestations.

  13. Differences in early speech patterns between Parkinson variant of multiple system atrophy and Parkinson's disease.

    PubMed

    Huh, Young Eun; Park, Jongkyu; Suh, Mee Kyung; Lee, Sang Eun; Kim, Jumin; Jeong, Yuri; Kim, Hee-Tae; Cho, Jin Whan

    2015-08-01

    In Parkinson variant of multiple system atrophy (MSA-P), patterns of early speech impairment and their distinguishing features from Parkinson's disease (PD) require further exploration. Here, we compared speech data among patients with early-stage MSA-P, PD, and healthy subjects using quantitative acoustic and perceptual analyses. Variables were analyzed for men and women in view of gender-specific features of speech. Acoustic analysis revealed that male patients with MSA-P exhibited more profound speech abnormalities than those with PD, regarding increased voice pitch, prolonged pause time, and reduced speech rate. This might be due to widespread pathology of MSA-P in nigrostriatal or extra-striatal structures related to speech production. Although several perceptual measures were mildly impaired in MSA-P and PD patients, none of these parameters showed a significant difference between patient groups. Detailed speech analysis using acoustic measures may help distinguish between MSA-P and PD early in the disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. FBXO7 immunoreactivity in α-synuclein-containing inclusions in Parkinson disease and multiple system atrophy.

    PubMed

    Zhao, Tianna; Severijnen, Lies-Anne; van der Weiden, Marcel; Zheng, Ping Pin; Oostra, Ben A; Hukema, Renate K; Willemsen, Rob; Kros, Johan M; Bonifati, Vincenzo

    2013-06-01

    Mutations in the gene encoding the F-box only protein 7 (FBXO7) cause PARK15, an autosomal recessive form of juvenile parkinsonism. Although the brain pathology in PARK15 patients remains unexplored, in vivo imaging displays severe loss of nigrostriatal dopaminergic terminals. Understanding the pathogenesis of PARK15 might therefore illuminate the mechanisms of the selective dopaminergic neuronal degeneration, which could also be important for understanding idiopathic Parkinson disease (PD). The expression of FBXO7 in the human brain remains poorly characterized, and its expression in idiopathic PD and different neurodegenerative diseases has not been investigated. Here, we studied FBXO7 protein expression in brain samples of normal controls (n = 9) and from patients with PD (n = 13), multiple system atrophy (MSA) (n = 5), Alzheimer disease (AD) (n = 5), and progressive supranuclear palsy (PSP) (n = 5) using immunohistochemistry with 2 anti-FBXO7 antibodies. We detected widespread brain FBXO7 immunoreactivity, with the highest levels in neurons of the cerebral cortex, putamen, and cerebellum. There were no major differences between normal and PD brains overall, but FBXO7 immunoreactivity was detected in large proportions of α-synuclein-positive inclusions (Lewy bodies, Lewy neurites, glial cytoplasmic inclusions), where it colocalized with α-synuclein in PD and MSA cases. By contrast, weak FBXO7 immunoreactivity was occasionally detected in tau-positive inclusions in AD and PSP. These findings suggest a role for FBXO7 in the pathogenesis of the synucleinopathies.

  15. Distinctive Features of NREM Parasomnia Behaviors in Parkinson’s Disease and Multiple System Atrophy

    PubMed Central

    Ratti, Pietro-Luca; Sierra-Peña, Maria; Manni, Raffaele; Simonetta-Moreau, Marion; Bastin, Julien; Mace, Harrison; Rascol, Olivier; David, Olivier

    2015-01-01

    Objective To characterize parasomnia behaviors on arousal from NREM sleep in Parkinson’s Disease (PD) and Multiple System Atrophy (MSA). Methods From 30 patients with PD, Dementia with Lewy Bodies/Dementia associated with PD, or MSA undergoing nocturnal video-polysomnography for presumed dream enactment behavior, we were able to select 2 PD and 2 MSA patients featuring NREM Parasomnia Behviors (NPBs). We identified episodes during which the subjects seemed to enact dreams or presumed dream-like mentation (NPB arousals) versus episodes with physiological movements (no-NPB arousals). A time-frequency analysis (Morlet Wavelet Transform) of the scalp EEG signals around each NPB and no- NPB arousal onset was performed, and the amplitudes of the spectral frequencies were compared between NPB and no-NPB arousals. Results 19 NPBs were identified, 12 of which consisting of ‘elementary’ NPBs while 7 resembling confusional arousals. With quantitative EEG analysis, we found an amplitude reduction in the 5-6 Hz band 40 seconds before NPBs arousal as compared to no-NPB arousals at F4 and C4 derivations (p<0.01). Conclusions Many PD and MSA patients feature various NREM sleep-related behaviors, with clinical and electrophysiological differences and similarities with arousal parasomnias in the general population. Significance This study help bring to attention an overlooked phenomenon in neurodegenerative diseases. PMID:25756280

  16. Distinct Functional and Macrostructural Brain Changes in Parkinson’s Disease and Multiple System Atrophy

    PubMed Central

    Planetta, Peggy J.; Kurani, Ajay S.; Shukla, Priyank; Prodoehl, Janey; Corcos, Daniel M.; Comella, Cynthia L.; McFarland, Nikolaus R.; Okun, Michael S.; Vaillancourt, David E.

    2016-01-01

    Parkinson’s disease (PD) and the parkinsonian variant of multiple system atrophy (MSAp) are neurodegenerative disorders that can be difficult to differentiate clinically. This study provides the first characterization of the patterns of task-related functional magnetic resonance imaging (fMRI) changes across the whole brain in MSAp. We used fMRI during a precision grip force task and also performed voxel-based morphometry (VBM) on T1-weighted images in MSAp patients, PD patients, and healthy controls. All groups were matched on age, and the patient groups had comparable motor symptom durations and severities. There were three main findings. First, MSAp and PD had reduced fMRI activation in motor control areas, including the basal ganglia, thalamus, insula, primary sensorimotor and prefrontal cortices, and cerebellum compared with controls. Second, there were no activation differences among the disease groups in the basal ganglia, thalamus, insula, or primary sensorimotor cortices, but PD had more extensive activation deficits throughout the cerebrum compared with MSAp and controls. Third, VBM revealed reduced volume in the basal ganglia, middle and inferior cerebellar peduncles, pons, and throughout the cerebrum in MSAp compared with controls and PD, and additionally throughout the cerebellar cortex and vermis in MSAp compared with controls. Collectively, these results provide the first evidence that fMRI activation is abnormal in the basal ganglia, cerebellum, and cerebrum in MSAp, and that a key distinguishing feature between MSAp and PD is the extensive and widespread volume loss throughout the brain in MSAp. PMID:25413603

  17. Differences in Dopaminergic Modulation to Motor Cortical Plasticity between Parkinson's Disease and Multiple System Atrophy

    PubMed Central

    Kawashima, Shoji; Ueki, Yoshino; Mima, Tatsuya; Fukuyama, Hidenao; Ojika, Kosei; Matsukawa, Noriyuki

    2013-01-01

    Dopamine modulates the synaptic plasticity in the primary motor cortex (M1). To evaluate whether the functioning of the cortico-striatal circuit is necessary for this modulation, we applied a paired associative stimulation (PAS) protocol that comprised an electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1, to 10 patients with Parkinson's disease (PD) and 10 with multiple system atrophy of the parkinsonian type (MSA-P) with and without dopamine replacement therapy (-on/off). To investigate the M1 function, motor-evoked potentials (MEPs) were measured before and after the PAS. In both patient groups without medication, the PAS protocol failed to increase the averaged amplitude of MEPs. The dopamine replacement therapy in PD, but not in MSA-P effectively restored the PAS-induced MEP increase. This suggests that not the existence of dopamine itself but the activation of cortico-striatal circuit might play an important role for cortical plasticity in the human M1. PMID:23658735

  18. Differences in dopaminergic modulation to motor cortical plasticity between Parkinson's disease and multiple system atrophy.

    PubMed

    Kawashima, Shoji; Ueki, Yoshino; Mima, Tatsuya; Fukuyama, Hidenao; Ojika, Kosei; Matsukawa, Noriyuki

    2013-01-01

    Dopamine modulates the synaptic plasticity in the primary motor cortex (M1). To evaluate whether the functioning of the cortico-striatal circuit is necessary for this modulation, we applied a paired associative stimulation (PAS) protocol that comprised an electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1, to 10 patients with Parkinson's disease (PD) and 10 with multiple system atrophy of the parkinsonian type (MSA-P) with and without dopamine replacement therapy (-on/off). To investigate the M1 function, motor-evoked potentials (MEPs) were measured before and after the PAS. In both patient groups without medication, the PAS protocol failed to increase the averaged amplitude of MEPs. The dopamine replacement therapy in PD, but not in MSA-P effectively restored the PAS-induced MEP increase. This suggests that not the existence of dopamine itself but the activation of cortico-striatal circuit might play an important role for cortical plasticity in the human M1.

  19. Nutritional Status and Changes in Body Weight in Patients with Multiple System Atrophy.

    PubMed

    Sato, Tomoe; Shiobara, Maho; Nishizawa, Masatoyo; Shimohata, Takayoshi

    2017-01-01

    The importance of nutritional management in neurodegenerative diseases is increasingly recognized in the clinical setting. However, few reports have examined the nutritional intake in patients with multiple system atrophy (MSA). Here, we investigated changes in daily caloric intake, body mass index (BMI) and nutritional status during the disease course of MSA. We performed a single-hospital study of 82 consecutive patients with probable MSA according to the consensus criteria. We determined daily caloric intake, the level of activities of daily living (ADL; independent, wheelchair-bound or bedridden) and BMI at the time of admission. Nutritional status was also evaluated using biochemical nutritional markers including serum albumin, total cholesterol and lymphocyte count. Although daily caloric intake decreased with ADL level deterioration (p < 0.01), no significant differences were observed in BMI among ADL levels. Serum albumin also decreased with ADL deterioration (p < 0.01); however, no significant differences were observed for serum total cholesterol or lymphocyte count with respect to ADL level. We demonstrated that patients with advanced stage MSA may develop malnutrition in the absence of a decrease in BMI. Moreover, serum albumin level may be useful for evaluating nutritional changes in MSA patients. © 2016 S. Karger AG, Basel.

  20. Impairment of brainstem implicit learning paradigms differentiates multiple system atrophy (MSA) from idiopathic Parkinson syndrome.

    PubMed

    von Lewinski, Friederike; Schwan, Michaela; Paulus, Walter; Trenkwalder, Claudia; Sommer, Martin

    2013-09-13

    Learning as measured by eyeblink classical conditioning is preserved in patients with idiopathic Parkinson's disease, but severely affected in patients with progressive supranuclear palsy. We here sought to clarify whether procedural learning is impaired in multiple system atrophy (MSA), and whether it may be helpful for the differentiation of parkinsonian syndromes. We investigated learning using (1) eyeblink classical conditioning with a delay (interstimulus interval 0 ms) and a trace (600 ms) paradigm and (2) a serial reaction time task. Participants were recruited from academic research centres. 11 patients with MSA and 11 healthy controls. Implicit learning in eyeblink classical conditioning (acquisition of conditioned responses) as well as the serial reaction time task measures of implicit learning (reaction time change) are impaired in patients with MSA as compared with controls, whereas explicit learning as measured by the sequence recall of the serial reaction time task is relatively preserved. We hypothesise that the learning deficits of patients with MSA are due to lesions of cerebellar and connected brainstem areas. A retrospective synopsis of these novel data on patients with MSA and groups of patients with idiopathic Parkinson's disease and progressive supranuclear palsy studied earlier suggest that eyeblink classical conditioning may contribute to the early differentiation of atypical Parkinson syndromes from idiopathic Parkinson's disease. This hypothesis should be tested in a prospective trial.

  1. Effects of daily water drinking on orthostatic and postprandial hypotension in patients with multiple system atrophy.

    PubMed

    Deguchi, Kazushi; Ikeda, Kazuyo; Sasaki, Iwao; Shimamura, Mieko; Urai, Yoshiteru; Tsukaguchi, Masago; Touge, Tetsuo; Takeuchi, Hiroaki; Kuriyama, Shigeki

    2007-06-01

    It has been demonstrated that the increased blood pressure (BP) caused by a single dose of water alleviates orthostatic hypotension (OH) and postprandial hypotension (PPH) in patients with autonomic failure (AF). The aim of this study was to evaluate the practical effect of daily water drinking on OH and PPH in the morning when patients with AF are usually most affected. In five patients with multiple system atrophy (MSA) characterized by intractable OH and PPH, we measured seated, standing and postprandial BP in the morning without and with ingestion of 350 ml tap water at 07.30 hours for seven successive days. The changes from the basal BP level at 07.30 hours (DeltaBP) were assessed as an index of the effect of water drinking. Water drinking elicited a rapid pressor response in all patients. The DeltaBP during sitting, standing and after a meal following water drinking (day 1 and day 7) was significantly higher than without water drinking (day 0). The effects of reducing OH and PPH on day 7 were equivalent to those on day 1. No adverse effects associated with daily water drinking were observed, except later diuresis, which occurred in one patient. Daily water drinking demonstrated constant pressor effects in the morning with no severe adverse effects in MSA patients. This finding suggests that water drinking should be tried as a practical measure to prevent or reduce OH and PPH.

  2. Novel treatment strategies targeting alpha-synuclein in multiple system atrophy as a model of synucleinopathy

    PubMed Central

    Valera, Elvira; Compagnoni, Giacomo Monzio; Masliah, Eliezer

    2016-01-01

    Neurodegenerative disorders with alpha-synuclein (α-syn) accumulation (synucleinopathies) include Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies and multiple system atrophy (MSA). Due to the involvement of toxic α-syn aggregates in the molecular origin of these disorders, developing effective therapies targeting α-syn is a priority as a disease-modifying alternative to current symptomatic treatments. Importantly, the clinical and pathological attributes of MSA make this disorder an excellent candidate as a synucleinopathy model for accelerated drug development. Recent therapeutic strategies targeting α-syn in in vivo and in vitro models of MSA, as well as in clinical trials, have been focused on the pathological mechanisms of α-syn synthesis, aggregation, clearance, and/or cell-to-cell propagation of its neurotoxic conformers. Here we summarize the most relevant approaches in this direction, with emphasis on their potential as general synucleinopathy modifiers, and enumerate research areas for potential improvement in MSA drug discovery. PMID:26924723

  3. Abnormal ghrelin secretion contributes to gastrointestinal symptoms in multiple system atrophy patients.

    PubMed

    Ozawa, Tetsutaro; Tokunaga, Jun; Arakawa, Musashi; Ishikawa, Atsushi; Takeuchi, Ryoko; Mezaki, Naomi; Miura, Takeshi; Sakai, Naoko; Hokari, Mariko; Takeshima, Akari; Utsumi, Kota; Kondo, Takashi; Yokoseki, Akio; Nishizawa, Masatoyo

    2013-08-01

    Patients with multiple system atrophy (MSA) often have evidence of compromised gastrointestinal motility. Ghrelin is a gut hormone that influences gastrointestinal motility in humans. The aim of this study was to determine whether ghrelin secretion is affected in MSA patients, and to investigate the relation between ghrelin secretion and gastrointestinal symptoms. Plasma levels of active ghrelin and unacylated ghrelin were measured in patients with MSA (n = 30), other atypical parkinsonian disorders including progressive supranuclear palsy-Richardson syndrome and corticobasal syndrome (n = 24), and control subjects (n = 24) using enzyme-linked immunosorbent assays. Gastrointestinal symptoms were quantified in all subjects using a self-report questionnaire. The ratio of active ghrelin to total ghrelin in the plasma (active ghrelin ratio) was lower in patients with MSA (mean: 8.0 %) than in patients with other atypical parkinsonian disorders (mean: 13.7 %, P = 0.001) and control subjects (mean: 13.9 %, P = 0.001). The active ghrelin ratio was correlated with the severity of gastrointestinal symptoms in MSA (r = -0.5, P = 0.004). Our observations indicate that ghrelin secretion is affected in patients with MSA. The low active ghrelin ratio may contribute to gastrointestinal symptoms in MSA.

  4. Brain structural profile of multiple system atrophy patients with cognitive impairment.

    PubMed

    Fiorenzato, Eleonora; Weis, Luca; Seppi, Klaus; Onofrj, Marco; Cortelli, Pietro; Zanigni, Stefano; Tonon, Caterina; Kaufmann, Horacio; Shepherd, Timothy Michael; Poewe, Werner; Krismer, Florian; Wenning, Gregor; Antonini, Angelo; Biundo, Roberta

    2017-03-01

    Current consensus diagnostic criteria for multiple system atrophy (MSA) consider dementia a non-supporting feature, although cognitive impairment and even frank dementia are reported in clinical practice. Mini-Mental State Examination (MMSE) is a commonly used global cognitive scale, and in a previous study, we established an MSA-specific screening cut-off score <27 to identify cognitive impairment. Finally, MSA neuroimaging findings suggest the presence of structural alterations in patients with cognitive deficits, although the extent of the anatomical changes is unclear. The aim of our multicenter study is to better characterize anatomical changes associated with cognitive impairment in MSA and to further investigate cortical and subcortical structural differences versus healthy controls (HC). We examined retrospectively 72 probable MSA patients [50 with normal cognition (MSA-NC) and 22 cognitively impaired (MSA-CI) based on MMSE <27] and compared them to 36 HC using gray- and white-matter voxel-based morphometry and fully automated subcortical segmentation. Compared to HC, MSA patients showed widespread cortical (bilateral frontal, occipito-temporal, and parietal areas), subcortical, and white-matter alterations. However, MSA-CI showed only focal volume reduction in the left dorsolateral prefrontal cortex compared with MSA-NC. These results suggest only a marginal contribution of cortical pathology to cognitive deficits. We believe that cognitive dysfunction is driven by focal fronto-striatal degeneration in line with the concept of "subcortical cognitive impairment".

  5. Dominant optic atrophy

    PubMed Central

    2012-01-01

    Definition of the disease Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC) and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3) encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8) are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7) are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of bilateral, mild

  6. [Posterior cortical atrophy (Benson-syndrome)].

    PubMed

    Rózsa, Anikó; Szilvássy, Ildikó; Kovács, Krisztina; Boór, Krisztina; Gács, Gyula

    2010-01-30

    We present the characteristics of posterior cortical atrophy--a very rare cortical dementia--in a 69 year old woman's case. Our patient's symptoms began with a visual problem which was initially explained by ophthalmological disorder. After neurological exam visual agnosia was diagnosed apart from other cognitive disorder (alexia without agraphia, acalculia, prosopagnosia, constructional disorder, clock-time recognition disorder, dressing apraxia, visuospatial disorientation). The brain MRI showed bilateral asymmetric parieto-occipital atrophy which is characteristic of posterior cortical atrophy.

  7. Skeletal muscle atrophy in bioengineered skeletal muscle: a new model system.

    PubMed

    Lee, Peter H U; Vandenburgh, Herman H

    2013-10-01

    Skeletal muscle atrophy has been well characterized in various animal models, and while certain pathways that lead to disuse atrophy and its associated functional deficits have been well studied, available drugs to counteract these deficiencies are limited. An ex vivo tissue-engineered skeletal muscle offers a unique opportunity to study skeletal muscle physiology in a controlled in vitro setting. Primary mouse myoblasts isolated from adult muscle were tissue engineered into bioartificial muscles (BAMs) containing hundreds of aligned postmitotic muscle fibers expressing sarcomeric proteins. When electrically stimulated, BAMs generated measureable active forces within 2-3 days of formation. The maximum isometric tetanic force (Po) increased for ∼3 weeks to 2587±502 μN/BAM and was maintained at this level for greater than 80 days. When BAMs were reduced in length by 25% to 50%, muscle atrophy occurred in as little as 6 days. Length reduction resulted in significant decreases in Po (50.4%), mean myofiber cross-sectional area (21.7%), total protein synthesis rate (22.0%), and noncollagenous protein content (6.9%). No significant changes occurred in either the total metabolic activity or protein degradation rates. This study is the first in vitro demonstration that length reduction alone can induce skeletal muscle atrophy, and establishes a novel in vitro model for the study of skeletal muscle atrophy.

  8. Reversible posterior leukoencephalopathy syndrome in a patient with multiple system atrophy: a possible association with oral midodrine treatment.

    PubMed

    Kim, Joong-Seok; Lee, Kwang-Soo; Lim, Sung-Chul; Ahn, Jae-Young; Song, In-Uk; Kim, Yeong-In; Kim, Bum-Soo; Kim, Hee-Tae

    2007-05-15

    We describe a 51-year-old man with a 3-year history of multiple system atrophy, who developed a reversible posterior leukoencephalopathy syndrome (RPLS) after receiving prescription midodrine for therapeutic treatment of orthostatic hypotension. Typical reversible magnetic resonance imaging findings, following treatment with midodrine, suggested a possible relationship between midodrine treatment, supine hypertension, and RPLS, although a cause-and-effect relationship cannot be confirmed. (c) 2007 Movement Disorder Society.

  9. Differing patterns of striatal sup 18 F-dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy

    SciTech Connect

    Brooks, D.J.; Ibanez, V.; Sawle, G.V.; Quinn, N.; Lees, A.J.; Mathias, C.J.; Bannister, R.; Marsden, C.D.; Frackowiak, R.S. )

    1990-10-01

    Using positron emission tomography (PET), we studied regional striatal 18F-dopa uptake in 16 patients with L-dopa-responsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age-matched normal volunteers. The patients with PD showed significantly reduced mean uptake of 18F-dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putamen was severely impaired (45% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean 18F-dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean 18F-dopa uptake in the anterior and posterior putamen. Caudate 18F-dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putamen. Mean 18F-dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal 18F-dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy.

  10. Computer-aided intelligent system for diagnosing pediatric asthma.

    PubMed

    Zolnoori, Maryam; Fazel Zarandi, Mohammad Hossein; Moin, Mostafa; Heidarnezhad, Hassan; Kazemnejad, Anoshirvan

    2012-04-01

    Asthma is a lung chronic inflammatory disorder estimated between 1.4% and 27.1% in different area of the world. Result of various studies show that asthma is usually underdiagnosed especially in developing countries, because of limitations on access to medical specialists and laboratory facilities. In this paper, we report on the development and evaluation of a novel patient-based fuzzy system that promotes the diagnosis method of asthma. The design of this application addresses five critical issues included: 1) modular representation of asthma diagnostic variables regard to patients' perception of the disease, 2) algorithmic approaches conducting inference of diagnosing based on patient's response to questions, 4) front-end mechanism for capturing data from patient, 5) output for both patient and physician regard to asthma possibility. for the system output score (0-10) the efficacy of this system calculated in the study sample included 139 asthmatic patients and 139 non-asthmatic patients (age range 6-18) reinforce the sensitivity of 88% and specificity of 100% for cut off value 0.7.

  11. A flash x-ray system for diagnosing liner implosions

    SciTech Connect

    Anderson, B. G.; Oro, D. M.; Olson, R. T.; Studebaker, J. K.; Platts, D.

    2003-01-01

    This paper describes a low energy flash X-ray system that is ideal for radiographing a wide variety of experimental phenomenon on both capacitor-bank pulsed power facilities and explosively driven magnetic-flux compression experiments. The versatility of this system has allowed us to obtain both single X-radiographs of imploding liners and multiple, temporally resolved radiographic sequences of target evolution. The dynamic liner radiographs are acquired with radially oriented X-ray heads that are instrumental for observing and diagnosing liner shape and symmetry, Rayleigh-Taylor instability growth, and liner-glide plane interaction (see Fig. 1). Multiframe radiographs acquired along the axis of a cylindrical target are used to provide physical data on phenomena such as shock-driven target hydrodynamics, Richtmyer-Meshkov instability growth, spall, fiction, and equations of state. The flexibility of this X-ray system has also allowed it to be successfully fielded both at various gas and powder gun facilities and explosively driven shock physics experiments.

  12. Preliminary study of intravenous amantadine treatment for ataxia management in patients with probable multiple system atrophy with predominant cerebellar ataxia.

    PubMed

    Youn, Jinyoung; Shin, Hyeeun; Kim, Ji Sun; Cho, Jin Whan

    2012-05-01

    Multiple system atrophy with predominant cerebellar ataxia is a disabling neurologic disease. However, effective management has not yet been established. We conducted a short-term, open-label preliminary study to assess the benefits of intravenous amantadine treatment in patients with probable multiple system atrophy with predominant cerebellar ataxia. Twenty patients (10 male, 10 female) with probable multiple system atrophy with predominant cerebellar ataxia received 400 mg of amantadine by intravenous per day for 5 days. Ataxia severity was evaluated by the International Cooperative Ataxia Rating Scale before and after intravenous amantadine therapy and all subjects reported subjective improvement after intravenous amantadine treatment using a patient global impression scale. We analyzed the total and subscale scores by the ataxia scale and patient global impression scale. The mean age was 57.4 years (range: 47-72) and the mean disease duration was 30.8 months (range: 11-79). The ataxia severity significantly decreased after intravenous amantadine therapy from 42.5 to 37.3 (p < 0.001). The mean patient global impression scale for improvement was 2.9 and there were no side effects of intravenous amantadine treatment observed. When we assessed responders, the duration of intravenous amantadine effect was more than 1 month in 4 subjects of 7 responders. Our findings suggest that intravenous amantadine treatment can be a safe management option in cerebellar ataxia, although the mechanism is unclear. Thus, further double-blind, long-term studies with a larger sample size are needed.

  13. The Experience of Families With Children With Spinal Muscular Atrophy Type I Across Health Care Systems.

    PubMed

    Murrell, Diane V; Lotze, Timothy E; Farber, Harold J; Crawford, Claire A; Wiemann, Constance M

    2017-10-01

    Spinal muscular atrophy type I is a genetic disease characterized by degeneration of spinal cord motor neurons resulting in weakness, technology dependence and early demise. While the newly approved treatment nusinersen may alter the morbidity/mortality of this disease there continues to be complex treatment challenges to consider. The aim of this qualitative study was to understand from the parent's perspective, experiences of the family and child in the emergency center, hospital, and clinical care settings to identify gaps in care. Nineteen families interviewed had 22 children with spinal muscular atrophy I (11 deceased, 11 living). Three overarching themes emerged from parent interviews describing a range of experiences surrounding diagnosis, informed medical decision making and acute care practice. Identified quality improvements include development of a diagnostic screening tool, a medical decision tool, and emergency center informational template individualized to the child and providing an overview of spinal muscular atrophy I.

  14. Regulatory circuitry of TWEAK-Fn14 system and PGC-1α in skeletal muscle atrophy program

    PubMed Central

    Hindi, Sajedah M.; Mishra, Vivek; Bhatnagar, Shephali; Tajrishi, Marjan M.; Ogura, Yuji; Yan, Zhen; Burkly, Linda C.; Zheng, Timothy S.; Kumar, Ashok

    2014-01-01

    Skeletal muscle wasting attributed to inactivity has significant adverse functional consequences. Accumulating evidence suggests that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and TNF-like weak inducer of apoptosis (TWEAK)-Fn14 system are key regulators of skeletal muscle mass in various catabolic states. While the activation of TWEAK-Fn14 signaling causes muscle wasting, PGC-1α preserves muscle mass in several conditions, including functional denervation and aging. However, it remains unknown whether there is any regulatory interaction between PGC-1α and TWEAK-Fn14 system during muscle atrophy. Here we demonstrate that TWEAK significantly reduces the levels of PGC-1α and mitochondrial content (∼50%) in skeletal muscle. Levels of PGC-1α are significantly increased in skeletal muscle of TWEAK-knockout (KO) and Fn14-KO mice compared to wild-type mice on denervation. Transgenic (Tg) overexpression of PGC-1α inhibited progressive muscle wasting in TWEAK-Tg mice. PGC-1α inhibited the TWEAK-induced activation of NF-κB (∼50%) and dramatically reduced (∼90%) the expression of atrogenes such as MAFbx and MuRF1. Intriguingly, muscle-specific overexpression of PGC-1α also prevented the inducible expression of Fn14 in denervated skeletal muscle. Collectively, our study demonstrates that TWEAK induces muscle atrophy through repressing the levels of PGC-1α. Overexpression of PGC-1α not only blocks the TWEAK-induced atrophy program but also diminishes the expression of Fn14 in denervated skeletal muscle.—Hindi, S. M., Mishra, V., Bhatnagar, S., Tajrishi, M. M., Ogura, Y., Yan, Z., Burkly, L. C., Zheng, T. S., Kumar, A. Regulatory circuitry of TWEAK-Fn14 system and PGC-1α in skeletal muscle atrophy program. PMID:24327607

  15. Heart rate circadian profile in the differential diagnosis between Parkinson disease and multiple system atrophy.

    PubMed

    Pilleri, Manuela; Levedianos, Giorgio; Weis, Luca; Gasparoli, Elisabetta; Facchini, Silvia; Biundo, Roberta; Formento-Dojot, Patrizia; Antonini, Angelo

    2014-02-01

    Clinical diagnostic criteria indicate presence of autonomic features as the primary hallmark of Multiple System Atrophy (MSA). However involvement of the autonomic system is also a recognized feature of Parkinson's Disease (PD), yielding a broad clinical overlap between the two diseases. Laboratory assessments may help in the differential diagnosis between PD and MSA. Ambulatory Monitoring of Blood Pressure (AMBP) is a suitable tool to study the circadian rhythm of blood pressure (BP) and heart rate (HR). Different studies reported a reduction of physiological BP nocturnal dipping in PD and MSA patients, but failed to identify a distinctive pattern discriminating the two diseases. On the other hand, HR nocturnal behavior has not been exhaustively analyzed. In the present study we compared the profiles of HR circadian rhythm in 61 PD and 19 MSA patients who underwent 24 h AMBP. We found higher nocturnal HR (nHR) (71.5 beats/min ± 7.4) in MSA compared with PD (63.8 beats/min ± 9.6) as well as significantly lower nocturnal decline of HR (ndHR) in MSA (7.3% ± 8.2) vs. PD (14% ± 7.5). At a Receiver Operating Curve analysis nHR and ndHR significantly discriminated MSA from PD. nHR showed a sensitivity of 84.2% and a specificity of 62.3% (AUC 0.76; 95% IC 0.65-0.85); ndHR showed a sensitivity of 68% of and a specificity of 77% (AUC 0.72; 95% IC 0.61-0.82). According to our findings, nHR is increased and ndHR is reduced in MSA compared to PD. Moreover, these two indices discriminate between the two diseases with acceptable accuracy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism

    PubMed Central

    Prusiner, Stanley B.; Woerman, Amanda L.; Mordes, Daniel A.; Watts, Joel C.; Rampersaud, Ryan; Berry, David B.; Patel, Smita; Oehler, Abby; Lowe, Jennifer K.; Kravitz, Stephanie N.; Geschwind, Daniel H.; Glidden, David V.; Halliday, Glenda M.; Middleton, Lefkos T.; Gentleman, Steve M.; Grinberg, Lea T.; Giles, Kurt

    2015-01-01

    Prions are proteins that adopt alternative conformations that become self-propagating; the PrPSc prion causes the rare human disorder Creutzfeldt–Jakob disease (CJD). We report here that multiple system atrophy (MSA) is caused by a different human prion composed of the α-synuclein protein. MSA is a slowly evolving disorder characterized by progressive loss of autonomic nervous system function and often signs of parkinsonism; the neuropathological hallmark of MSA is glial cytoplasmic inclusions consisting of filaments of α-synuclein. To determine whether human α-synuclein forms prions, we examined 14 human brain homogenates for transmission to cultured human embryonic kidney (HEK) cells expressing full-length, mutant human α-synuclein fused to yellow fluorescent protein (α-syn140*A53T–YFP) and TgM83+/− mice expressing α-synuclein (A53T). The TgM83+/− mice that were hemizygous for the mutant transgene did not develop spontaneous illness; in contrast, the TgM83+/+ mice that were homozygous developed neurological dysfunction. Brain extracts from 14 MSA cases all transmitted neurodegeneration to TgM83+/− mice after incubation periods of ∼120 d, which was accompanied by deposition of α-synuclein within neuronal cell bodies and axons. All of the MSA extracts also induced aggregation of α-syn*A53T–YFP in cultured cells, whereas none of six Parkinson’s disease (PD) extracts or a control sample did so. Our findings argue that MSA is caused by a unique strain of α-synuclein prions, which is different from the putative prions causing PD and from those causing spontaneous neurodegeneration in TgM83+/+ mice. Remarkably, α-synuclein is the first new human prion to be identified, to our knowledge, since the discovery a half century ago that CJD was transmissible. PMID:26324905

  17. Abnormal pulmonary function and respiratory muscle strength findings in Chinese patients with Parkinson's disease and multiple system atrophy--comparison with normal elderly.

    PubMed

    Wang, Yao; Shao, Wei-bo; Gao, Li; Lu, Jie; Gu, Hao; Sun, Li-hua; Tan, Yan; Zhang, Ying-dong

    2014-01-01

    There have been limited comparative data regarding the investigations on pulmonary and respiratory muscle function in the patients with different parkinsonism disorders such as Parkinson's disease (PD) and multiple system atrophy (MSA) versus normal elderly. The present study is aiming to characterize the performance of pulmonary function and respiratory muscle strength in PD and MSA, and to investigate the association with severity of motor symptoms and disease duration. Pulmonary function and respiratory muscle strength tests were performed in 30 patients with PD, 27 with MSA as well as in 20 age-, sex-, height-, weight-matched normal elderly controls. All the patients underwent United Parkinson's disease rating scale (UPDRS) or united multiple system atrophy rating scale (UMSARS) separately as diagnosed. Vital capacity, forced expiratory volume in 1 second and forced vital capacity decreased, residual volume and ratio of residual volume to total lung capacity increased in both PD and MSA groups compared to controls (p<0.05). Diffusing capacity was decreased in the MSA group, compared with PD and normal elderly control groups (p<0.05). Respiratory muscle strength was lower in both PD and MSA groups than in controls (p<0.05). The values representing spirometry function and respiratory muscle strength were found to have a negative linear correlation with mean score of UPDRS-III in PD and mean score of UMSARS-I in MSA. Respiratory muscle strength showed a negative linear correlation with the mean score of UMSARS-II and disease duration in MSA patients. These findings suggest that respiratory dysfunction is involved in PD and MSA. Respiratory muscle strength is remarkably reduced, and some of the parameters correlate with disease duration and illness severity. The compromised respiratory function in neurodegenerative disorders should be the focus of further researches.

  18. Distinct Neurochemical Profiles of Spinocerebellar Ataxias 1, 2, 6, and Cerebellar Multiple System Atrophy

    PubMed Central

    Öz, Gülin; Iltis, Isabelle; Hutter, Diane; Thomas, William; Bushara, Khalaf O.; Gomez, Christopher M.

    2011-01-01

    Hereditary and sporadic neurodegenerative ataxias are movement disorders that affect the cerebellum. Robust and objective biomarkers are critical for treatment trials of ataxias. In addition, such biomarkers may help discriminate between ataxia subtypes because these diseases display substantial overlap in clinical presentation and conventional MRI. Profiles of 10–13 neurochemical concentrations obtained in vivo by high field proton magnetic resonance spectroscopy (1H MRS) can potentially provide ataxia-type specific biomarkers. We compared cerebellar and brainstem neurochemical profiles measured at 4 T from 26 patients with spinocerebellar ataxias (SCA1, N=9; SCA2, N=7; SCA6, N=5) or cerebellar multiple system atrophy (MSA-C, N=5) and 15 age-matched healthy controls. The Scale for the Assessment and Rating of Ataxia (SARA) was used to assess disease severity. The patterns of neurochemical alterations relative to controls differed between ataxia types. Myo-inositol levels in the vermis, myo-inositol, total N-acetylaspartate, total creatine, glutamate, glutamine in the cerebellar hemispheres and myo-inositol, total N-acetylaspartate, glutamate in the pons were significantly different between patient groups (Bonferroni corrected p<0.05). The best MRS predictors were selected by a tree classification procedure and lead to 89% accurate classification of all subjects while the SARA scores overlapped considerably between patient groups. Therefore, this study demonstrated multiple neurochemical alterations in SCAs and MSA-C relative to controls and the potential for these neurochemical levels to differentiate ataxia types. Studies with higher numbers of patients and other ataxias are warranted to further investigate the clinical utility of neurochemical levels as measured by high-field MRS as ataxia biomarkers. PMID:20838948

  19. MicroRNAs in Cerebrospinal Fluid as Potential Biomarkers for Parkinson's Disease and Multiple System Atrophy.

    PubMed

    Marques, Tainá M; Kuiperij, H Bea; Bruinsma, Ilona B; van Rumund, Anouke; Aerts, Marjolein B; Esselink, Rianne A J; Bloem, Bas R; Verbeek, Marcel M

    2016-11-14

    Parkinson's disease (PD) and multiple system atrophy (MSA) are both part of the spectrum of neurodegenerative movement disorders and α-synucleinopathies with overlap of symptoms especially at early stages of the disease but with distinct disease progression and responses to dopaminergic treatment. Therefore, having biomarkers that specifically classify patients, which could discriminate PD from MSA, would be very useful. MicroRNAs (miRNAs) regulate protein translation and are observed in biological fluids, including cerebrospinal fluid (CSF), and may therefore have potential as biomarkers of disease. The aim of our study was to determine if miRNAs in CSF could be used as biomarkers for either PD or MSA. Using quantitative PCR (qPCR), we evaluated expression levels of 10 miRNAs in CSF patient samples from PD (n = 28), MSA (n = 17), and non-neurological controls (n = 28). We identified two miRNAs (miR-24 and miR-205) that distinguished PD from controls and four miRNAs that differentiated MSA from controls (miR-19a, miR-19b, miR-24, and miR-34c). Combinations of miRNAs accurately discriminated either PD (area under the curve (AUC) = 0.96) or MSA (AUC = 0.86) from controls. In MSA, we also observed that miR-24 and miR-148b correlated with cerebellar ataxia symptoms, suggesting that these miRNAs are involved in cerebellar degeneration in MSA. Our findings support the potential of miRNA panels as biomarkers for movement disorders and may provide more insights into the pathological mechanisms related to these disorders.

  20. Spinal Cord Lesion by Minor Trauma as an Early Sign of Multiple System Atrophy

    PubMed Central

    Brum, Marisa; Reimão, Sofia; Sousa, Djalma; de Carvalho, Rui; Ferreira, Joaquim J.

    2016-01-01

    Multiple system atrophy (MSA) is characterized clinically by parkinsonism, cerebellar, autonomic, and corticospinal features of variable severity. When the presentation is only parkinsonism, the disease might be difficult to differentiate from Parkinson’s disease (PD). We present a case of an 80-year-old man with previous diagnosis of PD. One year after the diagnosis, he had a whiplash cervical trauma due to a tricycle accident caused by a hole in the road. This low-energy trauma caused an unstable C4–C5 cervical fracture with spinal cord injury, which required surgical decompression and stabilization. Neurological examination showed marked postural instability, no rest and postural tremor, finger tapping slowed on the right, spastic tetraparesis (ASIA D) – predominantly on the left side, brisk deep tendon reflexes in the upper and lower extremities, and bilateral extensor plantar response. He also presented with vertical gaze restriction, mild hypometria in horizontal saccades, moderate dysphagia, and dysphonia. As atypical parkinsonism was suspected, he underwent an MRI that revealed conjunction of findings suggestive of parkinsonian-type MSA. In our case, we hypothesize that the loss of postural reflexes, as an early manifestation of MSA, did not allow the patient to have an effective reaction response to a low-energy trauma, resulting in a more severe injury. With this case report, we speculate that the severe spinal lesions caused by minor accidents can be an early sign of postural instability, which may lead to clinical suspicion of neurodegenerative disorder manifested by postural reflexes impairment. PMID:27014185

  1. Resistance training with instability in multiple system atrophy: a case report.

    PubMed

    Silva-Batista, Carla; Kanegusuku, Hélcio; Roschel, Hamilton; Souza, Eduardo O; Cunha, Telma F; Laurentino, Gilberto C; Manoel, N; De Mello, Marco T; Piemonte, Maria E P; Brum, Patrícia C; Forjaz, Claudia L; Tricoli, Valmor; Ugrinowitsch, Carlos

    2014-09-01

    This case report assessed quality of life, activities of daily living, motor symptoms, functional ability, neuromuscular parameters and mRNA expression of selected genes related to muscle protein synthesis and degradation in a patient with Multiple System Atrophy (MSA). The patient underwent resistance training with instability devices (i.e., bosu, dyna disk, balance disk, Swiss ball) for six months twice a week. After the six months training, the patient's left and right quadriceps muscle cross-sectional area and leg press one-repetition maximum increased 6.4%, 6.8%, and 40%, respectively; the patient's timed up and go, sit to stand, dynamic balance, and activities of daily living improved 33.3%, 28.6%, 42.3%, and 40.1%, respectively; the patient's severity of motor symptoms and risk of falls decreased 32% and 128.1%, respectively. Most of the subscales of quality of life demonstrated improvements as well, varying from 13.0% to 100.0%. mRNA expression of mechanogrowth factor and mammalian target of rapamycin increased 12.7-fold and 1.5-fold, respectively. This case report describes likely the first nonpharmacological therapeutic tool that might be able to decrease the severity of motor symptoms and risk of falls, and to improve functional ability, neuromuscular parameters, and quality of the life in a patient with MSA. Key pointsSix months of resistance training with instability alleviate the MSA-related effects and improve the quality of life in a patient with MSA.High complexity exercise intervention (i.e., resistance training with instability) may be very beneficial to individuals with impaired motor control and function as MSA patients.Caution should be exercised when interpreting our findings as they cannot be generalized to the entire MSA population and they do not allow establishing causal conclusions on the effects of this mode of exercise on MSA.

  2. Decreased Vesicular Storage and Aldehyde Dehydrogenase Activity in Multiple System Atrophy

    PubMed Central

    Goldstein, David S.; Sullivan, Patricia; Holmes, Courtney; Kopin, Irwin J.; Sharabi, Yehonatan; Mash, Deborah C.

    2015-01-01

    Background Parkinson disease (PD) and multiple system atrophy (MSA) share some neuropathologic findings (nigrostriatal dopaminergic lesion, alpha-synuclein deposition) but not others (Lewy bodies in PD, glial cytoplasmic inclusions in MSA). In PD evidence has accrued for a vesicular storage defect and aldehyde dehydrogenase (ALDH) inhibition in residual dopaminergic terminals, resulting in accumulation of the toxic dopamine (DA) metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). In this study we asked whether MSA entails a similar abnormal neurochemical pattern. Methods DA and its main neuronal metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE) and its main neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG), the catecholamine precursor DOPA, and DOPAL were measured in striatal and frontal cortical tissue from patients with pathologically proven end-stage MSA (N=15), sporadic PD (N=17), and control subjects (N=18). Results Compared to the control group, the MSA and PD groups had similarly decreased putamen DA (by 96% and 93%, p<0.0001), DOPAC (97% and 95%, p<0.0001), NE (91% and 74%, p<0.0001), and DHPG (81% and 74%, p<0.0001). In the MSA and PD groups, ratios of DOPAL:DA were 2.3 and 3.5 times control and DHPG:NE 3.1 and 2.6 times control, while DOPAC:DOPAL ratios were decreased by 61% and 74%. In both diseases cortical NE and DHPG were decreased, while DA and DOPAC were not. Conclusions MSA and PD entail a catecholamine metabolic profile indicating impaired vesicular storage, decreased ALDH activity, and DOPAL buildup, which may be part of a common pathway in catecholamine neuronal death. Targeting this pathway by interfering with catecholaldehyde production or effects constitutes a novel treatment approach. PMID:25829070

  3. Daytime sleepiness in Japanese patients with multiple system atrophy: prevalence and determinants

    PubMed Central

    2012-01-01

    Background The recent SLEEMSA study that evaluated excessive daytime sleepiness (EDS) in Caucasian patients with multiple system atrophy (MSA) demonstrated that EDS was more frequent in patients (28%) than in healthy subjects (2%). However, the prevalence and determinants of EDS in other ethnic populations have not been reported to date. Methods We performed a single-hospital prospective study on patients with probable MSA. To ascertain the prevalence and determinants of EDS in Japanese MSA patients, we assessed the patients’ degree of daytime sleepiness by using the Japanese version of the Epworth Sleepiness Scale (ESS). In addition, we investigated the effects of sleep-disordered breathing (SDB) and abnormal periodic leg movements in sleep (PLMS), which were measured by polysomnography, on the patients’ ESS scores. Results A total of 25 patients with probable MSA (21 patients with cerebellar MSA and 4 patients with parkinsonian MSA) were included in this study. All patients underwent standard polysomnography. The mean ESS score was 6.2 ± 0.9, and EDS was identified in 24% of the patients. SDB and abnormal PLMS were identified in 24 (96%) and 11 (44%) patients, respectively. The prevalences of EDS in patients with SDB and abnormal PLMS were 25% and 18%, respectively. No correlations were observed between ESS scores and the parameters of SDB or abnormal PLMS. Conclusions The frequency of EDS in Japanese patients with MSA was similar to that in Caucasian MSA patients. SDB and abnormal PLMS were frequently observed in MSA patients, although the severities of these factors were not correlated with EDS. Further investigations using objective sleep tests need to be performed. PMID:23116490

  4. Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy.

    PubMed

    Orimo, Satoshi; Kanazawa, Toshiro; Nakamura, Ayako; Uchihara, Toshiki; Mori, Fumiaki; Kakita, Akiyoshi; Wakabayashi, Koichi; Takahashi, Hitoshi

    2007-01-01

    Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [(123)I] MIBG myocardial scintigraphy, a sensitive biological marker for Parkinson's disease (PD), is related to cardiac sympathetic denervation in patients with PD. A slight decrease in cardiac uptake of MIBG has also been reported in some patients with multiple system atrophy (MSA). However, the pathophysiological mechanism accounting for the slight decrease in MIBG uptake in MSA remains to be elucidated. For confirmation, we examined cardiac tissue and sympathetic ganglia from patients with MSA. We immunohistochemically examined each specimen of 15 patients with MSA together with 10 control subjects using antibodies against tyrosine hydroxylase (TH) and neurofilament (NF). The number of TH-immunoreactive nerve fibers in the epicardium was preserved in 8 of 15 patients with MSA as well as in 10 control subjects. The number of TH-immunoreactive, but not of NF-immunoreactive nerve fibers in the epicardium was mildly or moderately decreased in six patients with MSA, of whom four showed a decrease of TH immunoreactivity in the neuronal somata in the sympathetic ganglia. Moreover, TH- and NF-immunoreactive nerve fibers almost entirely disappeared in the heart of one patient with MSA, in whom Lewy body pathology was present in the sympathetic ganglia. These findings suggest that mild degeneration of the cardiac sympathetic nerve can occur in MSA which is closely related to the pathological change of neurons in the sympathetic ganglia, accounting for the slight decrease in cardiac uptake of MIBG. Moreover, concurrent Lewy body pathology in the sympathetic ganglia might accelerate cardiac sympathetic denervation even in MSA.

  5. Resistance Training with Instability in Multiple System Atrophy: A Case Report

    PubMed Central

    Silva-Batista, Carla; Kanegusuku, Hélcio; Roschel, Hamilton; Souza, Eduardo O.; Cunha, Telma F.; Laurentino, Gilberto C.; Manoel, N.; De Mello, Marco T.; Piemonte, Maria E.P.; Brum, Patrícia C.; Forjaz, Claudia L.; Tricoli, Valmor; Ugrinowitsch, Carlos

    2014-01-01

    This case report assessed quality of life, activities of daily living, motor symptoms, functional ability, neuromuscular parameters and mRNA expression of selected genes related to muscle protein synthesis and degradation in a patient with Multiple System Atrophy (MSA). The patient underwent resistance training with instability devices (i.e., bosu, dyna disk, balance disk, Swiss ball) for six months twice a week. After the six months training, the patient’s left and right quadriceps muscle cross-sectional area and leg press one-repetition maximum increased 6.4%, 6.8%, and 40%, respectively; the patient’s timed up and go, sit to stand, dynamic balance, and activities of daily living improved 33.3%, 28.6%, 42.3%, and 40.1%, respectively; the patient’s severity of motor symptoms and risk of falls decreased 32% and 128.1%, respectively. Most of the subscales of quality of life demonstrated improvements as well, varying from 13.0% to 100.0%. mRNA expression of mechanogrowth factor and mammalian target of rapamycin increased 12.7-fold and 1.5-fold, respectively. This case report describes likely the first nonpharmacological therapeutic tool that might be able to decrease the severity of motor symptoms and risk of falls, and to improve functional ability, neuromuscular parameters, and quality of the life in a patient with MSA. Key points Six months of resistance training with instability alleviate the MSA-related effects and improve the quality of life in a patient with MSA. High complexity exercise intervention (i.e., resistance training with instability) may be very beneficial to individuals with impaired motor control and function as MSA patients. Caution should be exercised when interpreting our findings as they cannot be generalized to the entire MSA population and they do not allow establishing causal conclusions on the effects of this mode of exercise on MSA. PMID:25177187

  6. Breathing variability and brainstem serotonergic loss in a genetic model of multiple system atrophy.

    PubMed

    Flabeau, Olivier; Meissner, Wassilios G; Ozier, Annaig; Berger, Patrick; Tison, François; Fernagut, Pierre-Olivier

    2014-03-01

    Breathing disorders like sleep apnea, stridor, and dysrythmic breathing are frequent in patients with multiple system atrophy (MSA). These observations have been related to neurodegeneration in several pontomedullary respiratory nuclei and may explain the occurrence of sudden death. In this study, we sought to determine whether these functional and neuropathological characteristics could be replicated in a transgenic model of MSA. Mice expressing human wild-type α-synuclein under the control of the proteolipid promoter (PLP-αSYN) were compared with age-matched controls. Using whole-body, unrestrained plethysmography, the following breathing parameters were measured: inspiratory and expiratory times, tidal volume, expiratory volume, peak inspiratory and expiratory flows, and respiratory frequency. For each category, the mean, coefficient of variation, and irregularity score were analyzed. Brains were then processed for stereological cell counts of pontomedullary respiratory nuclei. A significant increase in the coefficient of variation and irregularity score was observed for inspiratory time, tidal volume, and expiratory volume in PLP-αSYN mice (P < 0.05). Glial cytoplasmic inclusions were found in the medullary raphe of PLP-αSYN mice, together with a loss of serotonergic immunoreactivity in the raphe obscurus (P < 0.001) and pallidus (P < 0.01). There was a negative correlation between α-synuclein burden and raphe pallidus cell counts (P < 0.05). There was no significant neuronal loss in the pre-Botzinger complex. The PLP-αSYN mouse model replicates the breathing variability and part of the neuronal depletion in pontomedullary respiratory nuclei observed in patients with MSA. Our findings support the use of this model for future candidate drugs in the breathing disorders observed in MSA. © 2014 International Parkinson and Movement Disorder Society.

  7. Depletion of putative chemosensitive respiratory neurons in the ventral medullary surface in multiple system atrophy.

    PubMed

    Benarroch, Eduardo E; Schmeichel, Ann M; Low, Phillip A; Parisi, Joseph E

    2007-02-01

    Multiple system atrophy (MSA) is a disorder that may manifest with reduced respiratory chemosensitivity and central sleep apnoea. Chemosensitive glutamatergic and serotonergic neurons located just beneath the ventral medullary surface, corresponding to the human arcuate nucleus (ArcN), have recently been implicated in control of automatic breathing in response to hypercapnia and hypoxia. We sought to determine whether these neurons were affected in MSA. Medullae were obtained at post-mortem from 11 patients (8 men, 3 women, age 64 +/- 3 years) with neuropathologically confirmed MSA and 11 control subjects (6 men and 5 women, age 66 +/- 4 years). Fifty micrometre sections obtained throughout the medulla were processed for vesicular glutamate transporter-2 (VGLUT-2), tryptophan-hydroxylase (TrOH), glial fibrillary acid protein (GFAP) and alpha-synuclein immunoreactivity. Cell counts, GFAP immunoreactivity and presence of glial cytoplasmic inclusions (GCIs) were assessed in the ArcN. In MSA, compared with controls, there was a marked depletion of ArcN neurons immunoreactive for either VGLUT-2 (74 +/- 21 versus 342 +/- 84 cells/section, P < 0.004) or TrOH (5 +/- 1 versus 16 +/- 2 cells/section, P < 0.001). There was also marked astrocytic gliosis and accumulation of alpha-synuclein immunoreactive GCIs in the ventral medullary surface in all cases. Our results indicate that there is severe loss of putative chemosensitive glutamatergic and serotonergic neurons as well as marked astrocytic gliosis in the ventral medullary surface in MSA. This may provide a possible morphological basis for impaired respiratory chemosensitivity and central sleep apnoea in this disorder.

  8. Health-related quality of life in multiple system atrophy and progressive supranuclear palsy.

    PubMed

    Winter, Yaroslav; Spottke, Annika E; Stamelou, Maria; Cabanel, Nicole; Eggert, Karla; Höglinger, Günter U; Sixel-Doering, Friederike; Herting, Birgit; Klockgether, Thomas; Reichmann, Heinz; Oertel, Wolfgang H; Dodel, Richard

    2011-01-01

    Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), known as atypical parkinsonian syndromes (APS), are neurodegenerative disorders with severe disability and decreased life expectancy. Little is known about the health-related quality of life (HrQoL) and its determinants in patients with those disorders. The objective of our cross-sectional study was to evaluate the HrQoL in patients with APS and to identify the determinants of HrQoL. A total of 101 consecutive patients with MSA (n = 54) and PSP (n = 47) were recruited in four German neurological centers. Disease severity was assessed using the Hoehn and Yahr stages and the Unified MSA Rating Scale. The HrQoL was evaluated using the EuroQol instrument (EQ-5D and EQ-VAS). Independent determinants of HrQoL were identified in multiple regression analyses. The mean EQ-VAS score was 52% lower than that reported for the general population (36.9 ± 18.3 vs. 77.4 ± 19.0). Of the study participants, 63% reported severe problems in at least one dimension of the EQ-5D. Cerebellar dysfunction was associated with a more considerable reduction of HrQoL. Independent determinants of reduced HrQoL were female gender, <12 years of education, disease severity, a decreased number of persons in the household and depression. The HrQoL in MSA and PSP is considerably reduced. While therapeutic options in the treatment of motor symptoms remain restricted, greater attention should be paid to the treatment of depression, which was identified among independent determinants of HrQoL. Independent determinants of HrQoL should be considered when developing healthcare programs aimed at improving the HrQoL in APS. Copyright © 2011 S. Karger AG, Basel.

  9. Clinical features and disability milestones in multiple system atrophy and progressive supranuclear palsy.

    PubMed

    Lee, Sang-Wook; Koh, Seong-Beom

    2012-10-01

    Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are an adult-onset progressive neurodegenerative disorder that are known to display diverse clinical features and disease progression. We aim to characterize the clinical features and disease progression in patients with MSA and PSP by using a number of relevant disability milestones in Koreans. Forty-one patients with MSA and 14 patients with PSP had been enrolled. The mean age at onset of MSA-C, MSA-P and PSP was 56.7 ± 7.8, 62.5 ± 8.0, 68.9 ± 6.1 years respectively. The most commonly reported symptom at disease onset is disequilibrium/dizziness in MSA-C, tremor in MSA-P and frequent falling in PSP. The mean duration of reaching milestones after disease onset in MSA-C were as followings: 20.8 (urinary incontinence), 22.9 (frequent falling), 27.8 (wheelchair bound), 31.8 (dysarthria) and 35.8 months (diagnosis). The mean duration of reaching milestones after disease onset were 22.0 (urinary incontinence), 32.6 (frequent falling and diagnosis), 41.2 (dysarthria), 61.4 months (wheelchair bound) in MSA-P and 16.8 (dysarthria), 21.6 (diagnosis), 21.7 (frequent falling), 24.0 months (wheel chair bound) in PSP. In the case of MSA, dizziness may occur for the first time. Thus, when the patient complains of non-specific dizziness, a follow-up examination to distinguish it from MSA can be helpful. There was a trend for patients with MSA-C to reach more disability milestones than in MSA-P and PSP before diagnosis. It may explain why patients with MSA-C are required more detail history taking and neurologic examination at an earlier stage.

  10. The involvement of supratentorial white matter in multiple system atrophy: a diffusion tensor imaging tractography study.

    PubMed

    Wang, Po-Shan; Yeh, Chien-Li; Lu, Chia-Feng; Wu, Hsiu-Mei; Soong, Bing-Wen; Wu, Yu-Te

    2017-03-01

    It has been assumed that cognitive disorder and visual-spatial disturbance in multiple system atrophy of the predominantly cerebellar type (MSA-C) are attributable to degradation of cerebellar function. The purpose of this study was to use diffusion tensor imaging (DTI) tractography to determine if patients with MSA-C characterized in part by visual-spatial disorders and cognitive disorders have changes of the structural connectivity network of nerve fibers, and to further describe the structural connectivity network. The study included 20 patients with MSA-C and 30 age- and sex-matched healthy controls. A 1.5T magnetic resonance imaging (MRI) scanner was used to obtain images for DTI tractography. Image preprocessing was done by large deformation diffeomorphic metric mapping. Whole-brain connectivity analysis was carried out. The patients had decreased numbers of long association fibers connecting the right parietal lobe to the frontal lobe. The commissural fibers and short association fibers connecting the bilateral frontal and occipital lobes and the number of short association fibers at the bilateral frontal and occipital region were also decreased significantly. The patients had a significant decrease in fiber density in the cerebellum compared to the healthy subjects. Our results provide DTI evidence suggesting that frontal and occipital white matter is involved in patients with MSA-C. This finding may correlate with their clinical symptoms such as cognitive disturbance as well as visual-spatial impairment. Therefore, cognitive disturbance and visual-spatial deficits in MSA-C might not be due to cerebellar lesions only as is widely believed but also involve cerebral lesions.

  11. Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: Case report and literature review

    PubMed Central

    Ogaki, Kotaro; Koga, Shunsuke; Aoki, Naoya; Lin, Wenlang; Suzuki, Kinuko; Ross, Owen A.; Dickson, Dennis W.

    2015-01-01

    X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy confirmed cases exceedingly rare. We report a 69-year-old white man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison’s disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities, and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss, and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of multiple system atrophy. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be

  12. Prodegenerative IκBα expression in oligodendroglial α-synuclein models of multiple system atrophy

    PubMed Central

    Kragh, Christine L.; Gysbers, Amanda M.; Rockenstein, Edward; Murphy, Karen; Halliday, Glenda M.; Masliah, Eliezer; Jensen, Poul Henning

    2016-01-01

    Multiple system atrophy is a progressive, neurodegenerative disease characterized by parkinsonism, ataxia, autonomic dysfunction, and accumulation of α-synuclein in oligodendrocytes. To understand how α-synuclein aggregates impact oligodendroglial homeostasis, we investigated an oligodendroglial cell model of α-synuclein dependent degeneration and identified responses linked to the NF-κB transcription factor stress system. Coexpression of human α-synuclein and the oligodendroglial protein p25α increased the expression of IκBα mRNA and protein early during the degenerative process and this was dependent on both aggregation and Ser129 phosphorylation of α-synuclein. This response was prodegenerative because blocking IκBα expression by siRNA rescued the cells. IκBα is an inhibitor of NF-κB and acts by binding and retaining NF-κB p65 in the cytoplasm. The protection obtained by silencing IκBα was accompanied by a strong increase in nuclear p65 translocation indicating that NF-κB activation protects against α-synuclein aggregate stress. In the cellular model, two different phenotypes were observed; degenerating cells retracting their microtubules and resilient cells tolerating the coexpression of α-synuclein and p25α. The resilient cells displayed a significant higher nuclear translocation of p65 and activation of the NF-κB system relied on stress elicited by aggregated and Ser129 phosphorylated α-synuclein. To validate the relationship between oligodendroglial α-synuclein expression and IκBα, we analyzed two different lines of transgenic mice expressing human α-synuclein under the control of the oligodendrocytic MBP promotor (intermediate-expresser line 1 and high-expresser line 29). IκBα mRNA expression was increased in both lines and immunofluorescence microscopy and in situ hybridization revealed that IκBα mRNA and protein is expressed in oligodendrocytes. IκBα mRNA expression was demonstrated prior to activation of microglia and

  13. Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration

    PubMed Central

    Yehoshua, Zohar; Filho, Carlos Alexandre de Amorim Garcia; Nunes, Renata Portella; Gregori, Giovanni; Penha, Fernando M.; Moshfeghi, Andrew A.; Zhang, Kang; Sadda, SriniVas; Feuer, William; Rosenfeld, Philip J.

    2014-01-01

    Purpose To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). Design Prospective, double-masked, randomized clinical trial. Participants Patients with GA measuring from 1.25 to 18 mm2 based on spectral-domain optical coherence tomography imaging. Methods Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and lowluminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores. Main Outcome Measures Change in area of GA at 26 weeks. Results Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55±0.94 and 2.02±0.74 mm in the eculizumab and placebo groups,respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19±0.12 and 0.18±0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37±0.22 mm in the eculizumab-treated eyes and by a mean of 0.37±0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified. Conclusions Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly

  14. [Posterior cortical atrophy].

    PubMed

    Solyga, Volker Moræus; Western, Elin; Solheim, Hanne; Hassel, Bjørnar; Kerty, Emilia

    2015-06-02

    Posterior cortical atrophy is a neurodegenerative condition with atrophy of posterior parts of the cerebral cortex, including the visual cortex and parts of the parietal and temporal cortices. It presents early, in the 50s or 60s, with nonspecific visual disturbances that are often misinterpreted as ophthalmological, which can delay the diagnosis. The purpose of this article is to present current knowledge about symptoms, diagnostics and treatment of this condition. The review is based on a selection of relevant articles in PubMed and on the authors' own experience with the patient group. Posterior cortical atrophy causes gradually increasing impairment in reading, distance judgement, and the ability to perceive complex images. Examination of higher visual functions, neuropsychological testing, and neuroimaging contribute to diagnosis. In the early stages, patients do not have problems with memory or insight, but cognitive impairment and dementia can develop. It is unclear whether the condition is a variant of Alzheimer's disease, or whether it is a separate disease entity. There is no established treatment, but practical measures such as the aid of social care workers, telephones with large keypads, computers with voice recognition software and audiobooks can be useful. Currently available treatment has very limited effect on the disease itself. Nevertheless it is important to identify and diagnose the condition in its early stages in order to be able to offer patients practical assistance in their daily lives.

  15. Validation of Autism Spectrum Disorder Diagnoses in Large Healthcare Systems with Electronic Medical Records

    ERIC Educational Resources Information Center

    Coleman, Karen J.; Lutsky, Marta A.; Yau, Vincent; Qian, Yinge; Pomichowski, Magdalena E.; Crawford, Phillip M.; Lynch, Frances L.; Madden, Jeanne M.; Owen-Smith, Ashli; Pearson, John A.; Pearson, Kathryn A.; Rusinak, Donna; Quinn, Virginia P.; Croen, Lisa A.

    2015-01-01

    To identify factors associated with valid Autism Spectrum Disorder (ASD) diagnoses from electronic sources in large healthcare systems. We examined 1,272 charts from ASD diagnosed youth <18 years old. Expert reviewers classified diagnoses as confirmed, probable, possible, ruled out, or not enough information. A total of 845 were classified with…

  16. Research on Key Technology in Remote Education System of Spirit Diagnosing by Eye in TCM

    ERIC Educational Resources Information Center

    Guo, Feng; Li, Shaozi; Dai, Ying; Zhou, Changle; Lin, Ying

    2011-01-01

    Spirit diagnosing is an important theory in TCM (Traditional Chinese Medicine), by which a TCM doctor can diagnose a patient's body state. But this theory is complicated and difficult to master simply learned from books. To further the theory and skill of spirit diagnosing, in this paper, the authors propose a remote education system that can…

  17. Research on Key Technology in Remote Education System of Spirit Diagnosing by Eye in TCM

    ERIC Educational Resources Information Center

    Guo, Feng; Li, Shaozi; Dai, Ying; Zhou, Changle; Lin, Ying

    2011-01-01

    Spirit diagnosing is an important theory in TCM (Traditional Chinese Medicine), by which a TCM doctor can diagnose a patient's body state. But this theory is complicated and difficult to master simply learned from books. To further the theory and skill of spirit diagnosing, in this paper, the authors propose a remote education system that can…

  18. Familial olivopontocerebellar atrophy with neonatal onset: a recessively inherited syndrome with systemic and biochemical abnormalities.

    PubMed Central

    Harding, B N; Dunger, D B; Grant, D B; Erdohazi, M

    1988-01-01

    Clinical and pathological findings are reported in two siblings who presented in the neonatal period with failure to thrive, hypotonia, pericardial effusions, limitation of joint movement, retinal dystrophy and loss of visual function. Additional features were biochemical evidence of purine overproduction and liver dysfunction. Post mortem, the neuropathological findings in both children were typical of olivopontocerebellar atrophy. It is suggested that the cases represent a recessively inherited inborn error of metabolism. Images PMID:3162953

  19. Tonic Electromyogram Density in Multiple System Atrophy with Predominant Parkinsonism and Parkinson's Disease

    PubMed Central

    Wang, Yi; Shen, Yun; Xiong, Kang-Ping; He, Pei-Cheng; Mao, Cheng-Jie; Li, Jie; Wang, Fu-Yu; Wang, Ya-Li; Huang, Jun-Ying; Liu, Chun-Feng

    2017-01-01

    Background: Both Parkinson's disease (PD) and multiple system atrophy (MSA) have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism (MSA-P) resembles PD in the manifestation of prominent parkinsonism. Whether the amount of rapid eye movement (REM) sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. Methods: This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder (RBD) prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram (EMG) activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. Results: No significant difference between MSA-P group and PD group had been found in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index (AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024) and higher tonic chin EMG density (34.02 [18.48, 57.18]% vs. 8.40 [3.11, 13.06]%, P < 0.001) as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA + RBD subgroup was higher than that in PD + RBD subgroup (55.04 [26.81, 69.62]% vs. 11.40 [8.51, 20.41]%, P < 0.001). Furthermore, no evidence of any difference in tonic EMG density emerged between PD + RBD and MSA - RBD subgroups (P > 0.05). Both disease duration (P = 0.056) and AHI (P = 0.051) showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD + RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of MSA-P (β = 0.552, P

  20. [Assessment of cognitive function, emotions and activities of daily living in patients with multiple system atrophy].

    PubMed

    Song, Dong-dong; Yu, Ying-xin; Dong, Qing-wen; Zhang, Hai-ling; Liu, Jian-guo; Liu, Qi; Yu, Jian; Qi, Xiao-kun

    2013-07-02

    To explore the cognitive function, emotional status and activities of daily living in patients with multiple system atrophy (MSA). Thirty-two MSA patients and 38 healthy controls from October 2009 to November 2012 were recruited from our hospital. Their cognitive function, emotional status and activities of daily living were assessed. Cognitive function was assessed by Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE); emotional status by self-rating depression scale (SDS) and self-rating anxiety scale (SAS); daily living and activities by activities of daily living scale (ADL). Data analysis was performed with SPSS 19.0. And the results were presented as the mean ± standard deviation. Comparison of means was performed with independent sample t test. And Pearson's correlation test was used for correlation analysis. A P-value <0.05 was considered significant. Mild or moderate cognitive impairment was documented in 71.9% of MSA patients. The scores of MoCA and MMSE in the MSA group were significantly lower than those in the control group. And the scores of ADL, SDS and SAS in the MSA group were significantly higher than those in the control group (P < 0.05). MoCA subitems such as space/executive function, attention, abstraction, language and delayed memory of the MSA group were significantly lower than those of the control group (P < 0.05). A negative correlation existed between the scores of MoCA and MMSE with disease duration (P < 0.01). There was a positive correlation between the scores of SDS and SAS with ADL and disease duration (P < 0.05). And the relationship was significant between the scores of SDS and SAS (P < 0.01). A positive correlation existed between scores of ADL with disease duration (P < 0.05). MSA patients have certain degrees of cognitive impairment, emotion disorders and impaired ADL. Cognitive impairment in MSA patients may be more common than previously. Furthermore, the clinical features of cognitive impairment in

  1. Videourodynamic and sphincter motor unit potential analyses in Parkinson's disease and multiple system atrophy

    PubMed Central

    Sakakibara, R; Hattori, T; Uchiyama, T; Yamanishi, T

    2001-01-01

    OBJECTIVES—Urinary dysfunction is a prominent autonomic feature in Parkinson's disease (PD) and multiple system atrophy (MSA), which is not only troublesome but also a cause of morbidity in these disorders. Recent advances in investigative uroneurology offer a better insight into the underlying pathophysiology and appropriate management for urinary dysfunction.
METHODS—twenty one patients with PD (15 men, six women, mean age 64 (49-76), mean disease duration 4 years (1-8 years), median Hoehn and Yahr grade 3 (1-4), all taking 300 mg/day of levodopa (100-500 mg)) and 15 with MSA (eight men, seven women, mean age 59 (48-72), mean disease duration 3 years (0.5-6 years)) were recruited. Videourodynamic and sphincter motor unit potential analyses in the patients with PD and MSA were carried out, looking for distinguishing hallmarks that might be useful in the differential diagnosis of these two diseases.
RESULTS—Urinary symptoms were found in 72% of patients with PD and in 100% with MSA. Filling phase abnormalities in the videourodynamic study included detrusor hyperreflexia in 81% of patients with PD and 56% with MSA, and uninhibited external sphincter relaxation in 33% of patients with PD and 33% of those with MSA. However, open bladder neck at the start of filling was not seen in patients with PD but was present in 53% of those with MSA, suggestive of internal sphincter denervation. Sphincter motor unit potential analysis showed neurogenic motor unit potentials in 5% of patients with PD and in 93% of those with MSA, suggestive of external sphincter denervation. On voiding, detrusor-external sphincter dyssynergia was not seen in patients with PD but was present in 47% of those with MSA. Pressure-flow analysis showed that the Abrams-Griffiths number, a grading of urethral obstruction (outflow obstruction >40), in PD (40 in women and 43 in men) was larger than that in MSA (12 in women and 28 in men). Weak detrusor in PD (66% of women and 40% of men) was less

  2. Natural History of Multiple System Atrophy in North America: A Prospective Cohort Study

    PubMed Central

    Low, Phillip A.; Reich, Stephen G.; Jankovic, Joseph; Shults, Clifford W.; Stern, Matthew B.; Novak, Peter; Tanner, Caroline M.; Gilman, Sid; Marshall, Frederick J.; Wooten, Frederick; Racette, Brad; Chelimsky, Thomas; Singer, Wolfgang; Sletten, David M.; Sandroni, Paola; Mandrekar, Jay

    2015-01-01

    Background Multiple system atrophy (MSA) is a rare, fatal neurodegenerative disorder exhibiting a combination of parkinsonism and/or cerebellar ataxia with autonomic failure. We report the first North American prospective natural history study of MSA, and the effects of phenotype and autonomic failure on prognosis. Methods 175 subjects with probable MSA, both MSA-P and MSA-C, were recruited and prospectively followed for 5 years with evaluations every 6 months in 12 centers. Natural history was evaluated by Kaplan-Meier survival analysis. We compared MSA-P with MSA-C and evaluated predictors of outcome. These subjects were evaluated with UMSARS I (a functional score of symptoms and ability to undertake activities of daily living), UMSARS II (neurological motor evaluation), and the Composite Autonomic Symptoms Scale (COMPASS)-select (a measure of autonomic symptoms and autonomic functional status. Findings Mean age of symptom onset was 63.4 (SD 8.57) years. Median survival from symptom onset by Kaplan-Meier analysis was 9.8 years (95% CI 8.8-10.7). Subjects with severe symptomatic autonomic failure (symptomatic orthostatic hypotension, urinary incontinence) at diagnosis had a worse prognosis, surviving 8.0 years (95% CI, 6.5-9.5, n=62) while remaining subjects survived a median of 10.3 years (95% CI, 9.3-11.4, n=113). At baseline MSA-P (n=126) and MSA-C (n=49) were not different in symptoms and function, UMSARS I, 25.2 (8.08) vs 24.6 (8.34), p=0.835; UMSARS II, 26.4 (8.77) vs 25.4 (10.51), p=0.7635; COMPASS_select), 43.5 (18.66) vs 42.8 (19.56), p=0.835. Progression, evaluated by change in UMSARS I, UMSARS II, COMPASS_select over the next 5 years, was not significantly different between MSA-P and MSA-C. Median time to death from enrollment baseline was 1.8 (95% CI, 0.9-2.7) years. Interpretation Probable MSA represents late-stage disease with short survival. Natural history of MSA-P and MSA-C are similar. Severe symptomatic autonomic failure at diagnosis is

  3. The Global Cognition, Frontal Lobe Dysfunction and Behavior Changes in Chinese Patients with Multiple System Atrophy

    PubMed Central

    Cao, Bei; Zhao, Bi; Wei, Qian-Qian; Chen, Ke; Yang, Jing; Ou, RuWei; Wu, Ying; Shang, Hui-Fang

    2015-01-01

    Background Studies on cognition in multiple system atrophy (MSA) patients are limited. Methods A total of 110 MSA patients were evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), Frontal Behavioral Inventory (FBI), and Unified MSA Rating Scale (UMSARS) tests. Fifty-five age-, sex-, education- and domicile-matched healthy controls were recruited to perform the FAB and ACE-R scales. Results Approximately 32.7% of the patients had global cognitive deficits with the most impaired domain being verbal fluency and visuospatial ability (26.4%), followed by memory (24.5%), language (20%) and orientation/attention (20%) based on a cut-off score of ACE-R ≤ 70. A total of 41.6% of the patients had frontal lobe dysfunction, with inhibitory control (60.9%) as the most impaired domain based on a cut-off score of FAB ≤14. Most patients (57.2%) showed moderate frontal behavior changes (FBI score 4–15), with incontinence (64.5%) as the most impaired domain. The binary logistic regression model revealed that an education level < 9 years (OR:13.312, 95% CI:2.931–60.469, P = 0.001) and UMSARS ≥ 40 (OR: 2.444, 95%CI: 1.002–5.962, P< 0.049) were potential determinants of abnormal ACE-R, while MSA-C (OR: 4.326, 95%CI: 1.631–11.477, P = 0.003), an education level < 9 years (OR:2.809 95% CI:1.060–7.444, P = 0.038) and UMSARS ≥ 40 (OR:5.396, 95%CI: 2.103–13.846, P < 0.0001) were potential determinants of abnormal FAB. Conclusions Cognitive impairment is common in Chinese MSA patients. MSA-C patients with low education levels and severe motor symptoms are likely to experience frontal lobe dysfunction, while MSA patients with low education levels and severe motor symptoms are likely to experience global cognitive deficits. These findings strongly suggest that cognitive impairment should not be an exclusion criterion for the diagnosis of MSA. PMID:26431430

  4. Topographical differences of brain iron deposition between progressive supranuclear palsy and parkinsonian variant multiple system atrophy.

    PubMed

    Han, Yong-Hee; Lee, Jae-Hyeok; Kang, Bok-Man; Mun, Chi-Woong; Baik, Seung-Kug; Shin, Yong-Il; Park, Kyu-Hyun

    2013-02-15

    There have been various studies showing increased iron levels in parkinsonian disorders. The purpose of this study was to demonstrate topographical differences of brain iron deposition between progressive supranuclear palsy (PSP) and the parkinsonian variant of multiple system atrophy (MSA-p) with SWI images. A total of 11 patients with PSP, 12 with MSA-p, 15 with Parkinson's disease (PD), and 20 age-matched healthy controls underwent SWI of the brain. Mean phase shift values of the red nucleus (RN), substantia nigra (SN), head of the caudate nucleus (CN), globus pallidus (GP), putamen (PUT), and thalamus (TH) were calculated and compared between groups. A voxel-based analysis of the processed SWI was performed to determine topographical differences of iron-related hypointense signals in PUT, GP, and TH. Patients with PSP and MSA-p had significantly higher levels of iron deposition than control and PD groups. Comparing patients with PSP and MSA-p, differences were found in iron concentrations of the RN, SN, GP, and TH, which were higher in the PSP group. However, iron levels in the PUT were higher in the MSA group (p<0.05). The area under curve (AUC) indicated that the PUT was the most valuable nucleus in differentiating MSA-p from PSP and PD according to phase shift values (AUC=0.836). Meanwhile the GP (AUC=0.869) and TH (AUC=0.884) were the two most valuable nuclei in differentiating PSP from MSA-p and PD. Voxel-based analysis showed subregional differences in iron-related hypointense signals in the PUT, GP, and TH between MSA-p and PSP groups. Patients with MSA-p had significant increases of iron-related hypointense signals in the posterolateral PUT and adjacent lateral aspect of the GP, whereas the PSP group had increased hypodense signals in the anterior and medial aspects of the GP and TH. Our data demonstrate that pathological iron accumulations are more prevalent and severe in PSP compared to MSA-p. The distribution of high-iron-content regions in this

  5. A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

    PubMed Central

    Rolland, Yan; Vérin, Marc; Payan, Christine A; Duchesne, Simon; Kraft, Eduard; Hauser, Till K; Jarosz, Josef; Deasy, Neil; Defevbre, Luc; Delmaire, Christine; Dormont, Didier; Ludolph, Albert C; Bensimon, Gilbert

    2011-01-01

    Aim To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. Methods The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP=362, MSA=398), 627 had per protocol images (PSP=297, MSA=330). Intra-rater (n=60) and inter-rater (n=555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n=441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. Results Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75–0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1–F2; MSA: F2–F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. Conclusions The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with

  6. The natural history of multiple system atrophy: a prospective European cohort study.

    PubMed

    Wenning, Gregor K; Geser, Felix; Krismer, Florian; Seppi, Klaus; Duerr, Susanne; Boesch, Sylvia; Köllensperger, Martin; Goebel, Georg; Pfeiffer, Karl P; Barone, Paolo; Pellecchia, Maria Teresa; Quinn, Niall P; Koukouni, Vasiliki; Fowler, Clare J; Schrag, Anette; Mathias, Christopher J; Giladi, Nir; Gurevich, Tanya; Dupont, Erik; Ostergaard, Karen; Nilsson, Christer F; Widner, Håkan; Oertel, Wolfgang; Eggert, Karla Maria; Albanese, Alberto; del Sorbo, Francesca; Tolosa, Eduardo; Cardozo, Adriana; Deuschl, Günther; Hellriegel, Helge; Klockgether, Thomas; Dodel, Richard; Sampaio, Cristina; Coelho, Miguel; Djaldetti, Ruth; Melamed, Eldad; Gasser, Thomas; Kamm, Christoph; Meco, Giuseppe; Colosimo, Carlo; Rascol, Olivier; Meissner, Wassilios G; Tison, François; Poewe, Werner

    2013-03-01

    Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1-11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09-3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02-4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5-0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1-10·2; p=0·03) predicted rapid UMSARS progression. Sample size

  7. Probable hereditary multiple system atrophy-autonomic (MSA-A) in a family in the United States.

    PubMed

    Hohler, A D; Singh, V J

    2012-03-01

    Multiple system atrophy-autonomic (MSA-A) is a typically spontaneous neurological disorder. The disease, distinguished by a "hot cross bun" sign on MRI, causes a series of autonomic dysfunctions including orthostatic hypotension and genitourinary and gastrointestinal problems. We present an 84 year-old woman with MSA-A symptoms who was positive for a "hot cross bun" sign. Genetic testing was used to rule out other possible ataxias. Importantly, the patient's two sisters also presented with similar symptoms indicating a possible autosomal dominant linkage. To our knowledge, this is the first report of hereditary MSA-A in the USA.

  8. [Multiple system atrophy and Alzheimer's disease: a case report of a rare association of two neuro-degenerative disorders].

    PubMed

    Rusina, R; Bourdain, F; Matej, R

    2007-12-01

    Multiple system atrophy (MSA) is a neurodegenerative disorder typically characterised by cerebellar dysfunction, parkinsonism, pyramidal signs and dysautonomy. Cognitive impairement is usually limited to a moderate subcortical dysexecutive syndrom. We report the case of a 62-year-old woman suffering from MSA who progressively developed severe dementia. Neuropathological examination confirmed the diagnosis of definite MSA and also showed histopathological hallmarks of Alzheimer's disease. This association is extremely rare in the literature. Our observation confirmes that franc dementia in MSA should prompt a search for another associated cause and underlines the usefulness of neuropathological verifications in atypical clinical pictures.

  9. [Laryngeal paralysis and olivopontocerebellar atrophy. Apropos of a case].

    PubMed

    Sánchez Segura, A; Ramos Pérez, P L; Rodríguez Sánchez, A; Aguirre Sánchez, J J; Gutiérrez Díez, J A; Alvarez Domínguez, J

    1990-01-01

    We display the study performed to a female patient affected of laryngeal paralysis to become, based in clinical and radiologic criteria, to diagnose her cerebellar atrophy. We justify our work because of how infrequently this illness heredodegenerative of the central nervous system begins with cranial pairs paralysis. We emphasize the importance that the new methods of explorations specially TAC and IRM, have to guess the possible etiologies of central originated paralysis.

  10. Depletion of medullary serotonergic neurons in patients with multiple system atrophy who succumbed to sudden death.

    PubMed

    Tada, Mari; Kakita, Akiyoshi; Toyoshima, Yasuko; Onodera, Osamu; Ozawa, Tetsutaro; Morita, Takashi; Nishizawa, Masatoyo; Takahashi, Hitoshi

    2009-07-01

    Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by prominent autonomic failure with ataxia and/or parkinsonism. The leading cause of death in MSA is sudden death. We have shown that the early development of autonomic failure is an independent risk factor for sudden death. The depletion of sympathetic preganglionic neurons in the spinal intermediolateral cell column (IML) and its afferent medullary catecholaminergic and serotonergic neurons has been proposed to be partly responsible for autonomic failure in MSA. In this study, we investigated whether the depletion of neurons in any of these autonomic neuron groups contributes to sudden death in MSA. Out of 52 autopsy-proven patients with MSA, we selected 12 individuals who had died within 3.5 years after disease onset to define the accurate levels of slices and identify early neuropathological changes of autonomic nuclei in MSA. Four patients succumbed to sudden death and eight patients died through established causes. Serial 10 mum sections were obtained from the 8th segment of the thoracic cord and the rostral medulla oblongata. Sections from the medulla oblongata were immunostained for thyrosine hydroxylase and tryptophan hydroxylase. The total cell number in the five sections was computed for comparison. Compared with the control, the MSA group showed a marked depletion of neurons in the IML (38.0 +/- 7.1 versus 75.2 +/- 7.6 cells, P < 0.001), thyrosine hydroxylase-immunoreactive neurons in the ventrolateral medulla (VLM) (17.4 +/- 5.1 versus 72.8 +/- 13.6 cells, P < 0.01) and tryptophan hydroxylase-immunoreactive neurons in the VLM (15.6 +/- 9.2 versus 60.8 +/- 17.0 cells, P < 0.01), nucleus raphe obscurus (19.3 +/- 4.4 versus 75.3 +/- 8.6 cells, P < 0.001), nucleus raphe pallidus (2.1 +/- 2.7 versus 9.0 +/- 3.4 cells, P < 0.03), and arcuate nucleus (0.4 +/- 0.8 versus 2.3 +/- 1.5 cells, P < 0.05). Moreover, in patients who succumbed to sudden death, when compared with patients who

  11. Regulatory circuitry of TWEAK-Fn14 system and PGC-1α in skeletal muscle atrophy program.

    PubMed

    Hindi, Sajedah M; Mishra, Vivek; Bhatnagar, Shephali; Tajrishi, Marjan M; Ogura, Yuji; Yan, Zhen; Burkly, Linda C; Zheng, Timothy S; Kumar, Ashok

    2014-03-01

    Skeletal muscle wasting attributed to inactivity has significant adverse functional consequences. Accumulating evidence suggests that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and TNF-like weak inducer of apoptosis (TWEAK)-Fn14 system are key regulators of skeletal muscle mass in various catabolic states. While the activation of TWEAK-Fn14 signaling causes muscle wasting, PGC-1α preserves muscle mass in several conditions, including functional denervation and aging. However, it remains unknown whether there is any regulatory interaction between PGC-1α and TWEAK-Fn14 system during muscle atrophy. Here we demonstrate that TWEAK significantly reduces the levels of PGC-1α and mitochondrial content (∼50%) in skeletal muscle. Levels of PGC-1α are significantly increased in skeletal muscle of TWEAK-knockout (KO) and Fn14-KO mice compared to wild-type mice on denervation. Transgenic (Tg) overexpression of PGC-1α inhibited progressive muscle wasting in TWEAK-Tg mice. PGC-1α inhibited the TWEAK-induced activation of NF-κB (∼50%) and dramatically reduced (∼90%) the expression of atrogenes such as MAFbx and MuRF1. Intriguingly, muscle-specific overexpression of PGC-1α also prevented the inducible expression of Fn14 in denervated skeletal muscle. Collectively, our study demonstrates that TWEAK induces muscle atrophy through repressing the levels of PGC-1α. Overexpression of PGC-1α not only blocks the TWEAK-induced atrophy program but also diminishes the expression of Fn14 in denervated skeletal muscle.

  12. Learning about Spinal Muscular Atrophy

    MedlinePlus

    ... Disorders 2003 News Release Fischbeck Group Learning About Spinal Muscular Atrophy What is spinal muscular atrophy? What are the ... Additional Resources for Spinal Muscular Atrophy What is spinal muscular atrophy? Spinal muscular atrophy is a group of inherited ...

  13. Cognitive deficits in progressive supranuclear palsy, Parkinson's disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction.

    PubMed Central

    Robbins, T W; James, M; Owen, A M; Lange, K W; Lees, A J; Leigh, P N; Marsden, C D; Quinn, N P; Summers, B A

    1994-01-01

    Groups of patients with idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy or Steele-Richardson-Olszewski syndrome, matched for overall clinical disability, were compared using three computerised cognitive tests previously shown to be sensitive to frontal lobe dysfunction. On a test of planning based on the Tower of London task, all three groups were impaired, but in different ways. The groups with palsy and Parkinson's disease were slower in the measure of initial thinking time, whereas the group with multiple system atrophy was only slower in a measure of thinking time subsequent to the first move, resembling patients with frontal lobe damage. On a test of spatial working memory, each group showed deficits relative to their matched control groups, but the three groups differed in their strategy for dealing with this task. On a test of attentional set shifting, each group was again impaired, mainly at the extradimensional shifting stage, but the group with Steele-Richardson-Olszewski syndrome exhibited the greatest deficit. The results are compared with previous findings in patients with Alzheimer's disease or frontal lobe damage. It is concluded that these basal ganglia disorders share a distinctive pattern of cognitive deficits on tests of frontal lobe dysfunction, but there are differences in the exact nature of the impairments, in comparison not only with frontal lobe damage but also with one another. PMID:8301310

  14. The natural history of multiple system atrophy: a prospective European cohort study

    PubMed Central

    Wenning, Gregor K; Geser, Felix; Krismer, Florian; Seppi, Klaus; Duerr, Susanne; Boesch, Sylvia; Köllensperger, Martin; Goebel, Georg; Pfeiffer, Karl P; Barone, Paolo; Pellecchia, Maria Teresa; Quinn, Niall P; Koukouni, Vasiliki; Fowler, Clare J; Schrag, Anette; Mathias, Christopher J; Giladi, Nir; Gurevich, Tanya; Dupont, Erik; Ostergaard, Karen; Nilsson, Christer F; Widner, Håkan; Oertel, Wolfgang; Eggert, Karla Maria; Albanese, Alberto; del Sorbo, Francesca; Tolosa, Eduardo; Cardozo, Adriana; Deuschl, Günther; Hellriegel, Helge; Klockgether, Thomas; Dodel, Richard; Sampaio, Cristina; Coelho, Miguel; Djaldetti, Ruth; Melamed, Eldad; Gasser, Thomas; Kamm, Christoph; Meco, Giuseppe; Colosimo, Carlo; Rascol, Olivier; Meissner, Wassilios G; Tison, François; Poewe, Werner

    2013-01-01

    Summary Background Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. Methods Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. Findings 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1–11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09–3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02–4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5–0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1–10·2; p=0·03) predicted

  15. Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure.

    PubMed

    Cunha, Telma F; Bacurau, Aline V N; Moreira, Jose B N; Paixão, Nathalie A; Campos, Juliane C; Ferreira, Julio C B; Leal, Marcelo L; Negrão, Carlos E; Moriscot, Anselmo S; Wisløff, Ulrik; Brum, Patricia C

    2012-01-01

    Heart failure (HF) is known to lead to skeletal muscle atrophy and dysfunction. However, intracellular mechanisms underlying HF-induced myopathy are not fully understood. We hypothesized that HF would increase oxidative stress and ubiquitin-proteasome system (UPS) activation in skeletal muscle of sympathetic hyperactivity mouse model. We also tested the hypothesis that aerobic exercise training (AET) would reestablish UPS activation in mice and human HF. Time-course evaluation of plantaris muscle cross-sectional area, lipid hydroperoxidation, protein carbonylation and chymotrypsin-like proteasome activity was performed in a mouse model of sympathetic hyperactivity-induced HF. At the 7(th) month of age, HF mice displayed skeletal muscle atrophy, increased oxidative stress and UPS overactivation. Moderate-intensity AET restored lipid hydroperoxides and carbonylated protein levels paralleled by reduced E3 ligases mRNA levels, and reestablished chymotrypsin-like proteasome activity and plantaris trophicity. In human HF (patients randomized to sedentary or moderate-intensity AET protocol), skeletal muscle chymotrypsin-like proteasome activity was also increased and AET restored it to healthy control subjects' levels. Collectively, our data provide evidence that AET effectively counteracts redox imbalance and UPS overactivation, preventing skeletal myopathy and exercise intolerance in sympathetic hyperactivity-induced HF in mice. Of particular interest, AET attenuates skeletal muscle proteasome activity paralleled by improved aerobic capacity in HF patients, which is not achieved by drug treatment itself. Altogether these findings strengthen the clinical relevance of AET in the treatment of HF.

  16. Spinal Muscular Atrophy

    MedlinePlus

    ... here Home » Disorders » Patient & Caregiver Education » Fact Sheets Spinal Muscular Atrophy Fact Sheet What is spinal muscular atrophy? What ... Where can I get more information? What is spinal muscular atrophy? Spinal muscular atrophy (SMA) is one of several ...

  17. Diagnosing the ZEUS experiment with the ZEX expert system

    SciTech Connect

    Behrens, U.; Flasinski, M.; Hagge, L.; Ohrenberg, K.

    1994-12-31

    ZEX is an expert system being developed to support operation of the ZEUS experiment. Based on the experience gained with a prototype version of the expert system, it was decided to implement the final system using a commercial expert system shell. Task of the expert system is to monitor all fields of information available online to achieve the highest efficiency of data taking by minimizing dead time of the detector and ensuring high quality of the data written to tape.

  18. Fault Diagnosis in Discrete-Event Systems with Incomplete Models: Learnability and Diagnosability.

    PubMed

    Kwong, Raymond H; Yonge-Mallo, David L

    2015-07-01

    Most model-based approaches to fault diagnosis of discrete-event systems require a complete and accurate model of the system to be diagnosed. However, the discrete-event model may have arisen from abstraction and simplification of a continuous time system, or through model building from input-output data. As such, it may not capture the dynamic behavior of the system completely. In a previous paper, we addressed the problem of diagnosing faults given an incomplete model of the discrete-event system. We presented the learning diagnoser which not only diagnoses faults, but also attempts to learn missing model information through parsimonious hypothesis generation. In this paper, we study the properties of learnability and diagnosability. Learnability deals with the issue of whether the missing model information can be learned, while diagnosability corresponds to the ability to detect and isolate a fault after it has occurred. We provide conditions under which the learning diagnoser can learn missing model information. We define the notions of weak and strong diagnosability and also give conditions under which they hold.

  19. Diagnosing Trouble Spots Caused by an Irrigation System

    Treesearch

    John R. Scholtes

    2002-01-01

    I discuss a testing procedure to determine the water distribution pattern of a sprinkler irrigation system and steps that may be taken to improve uniformity of application. All irrigation systems require testing and maintenance to assure that water application is as uniform as possible. Even new systems installed to a manufacturer's specifications should be "...

  20. Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: case report and literature review.

    PubMed

    Ogaki, Kotaro; Koga, Shunsuke; Aoki, Naoya; Lin, Wenlang; Suzuki, Kinuko; Ross, Owen A; Dickson, Dennis W

    2016-02-01

    X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy-confirmed cases exceedingly rare. We report a 69-year-old White man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison's disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of MSA. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting the optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be considered in the

  1. Morphological substrate of autonomic failure and neurohormonal dysfunction in multiple system atrophy: impact on determining phenotype spectrum.

    PubMed

    Ozawa, Tetsutaro

    2007-09-01

    Autonomic failure is a prominent clinical feature of patients with multiple system atrophy (MSA). Neurohormonal dysfunction is also a frequent accompaniment in patients with MSA. The determination of the pathological involvement of the autonomic neurons, which are responsible for circadian rhythms and responses to stress, provides new insight into autonomic failure and neurohormonal dysfunction in MSA. The disruptions of circadian rhythms and responses to stress may underlie the impairment of homeostatic integration responsible for cardiovascular and respiratory failures. These notions lead to the hypothesis that a pathological involvement of autonomic neurons is a significant factor of the poor prognosis of MSA. Beyond this perspective, endeavors to find the morphological phenotype that represents a predominant loss of autonomic neurons may elucidate the full spectrum of pathological involvements in MSA.

  2. [Obese woman presenting as vocal cord abductor paralysis and floppy arytenoid associated with early signs of multiple system atrophy].

    PubMed

    Sakuta, Hideki; Miyamoto, Masayuki; Suzuki, Keisuke; Miyamoto, Tomoyuki; Nakajima, Itsuo; Nakamura, Toshiki; Hirata, Koichi

    2012-01-01

    In multiple system atrophy (MSA), sleep-related breathing disorders are commonly observed, including vocal cord abductor paralysis (VCAP), which can cause sudden death. In its early stage, VCAP occurs only during sleep, but as the disease progresses, it appears when both awake and asleep. We encountered a 59-year-old obese woman who had been under continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea syndrome (OSAS) for approximately one year but later developed acute respiratory failure because of VCAP. VCAP was the predominant finding that led to the diagnosis of MSA in our patient. On laryngoscopic examination, the movement of the patient's larynx was normal during wakefulness, but VCAP, paradoxical movements of the vocal cord and a floppy arytenoid were observed during drug-induced sleep. We suggest that detection of VCAP and laryngopharyngeal abnormalities such as floppy arytenoid in the early stage of MSA is important for determining treatment options.

  3. Differential diagnostic relevance of high resolution magnetic resonance in patients with possible multiple system atrophy (MSA) - A case report.

    PubMed

    Baronica, Koraljka Bacić; Ivkić, Goran; Ozretić, David; Milicević, Goran

    2011-01-01

    Multiple system atrophy (MSA) is sporadic, progressive neurodegenerative disorder characterized clinically by autonomic dysfunction, Parkinsonism (MSA-P), and cerebellar ataxia (MSA-C) in any combination. Parkinsonism is present in the majority of patients (80%). Early in the course of the disease autonomic dysfunctions are present in approximately 40% of patients, while the domination of cerebellar symptoms is present in 20% of all patients. According to second consensus statement on diagnosis of MSA, to make the diagnosis of possible MSA, except Parkinsonism or a cerebellar syndrome, there must be one feature involving autonomic dysfunction plus one other additional that can include findings on history, clinical examination or changes in structural or functional imaging. We present a case of 60-year old male with Parkinsonism and cerebellar symptoms accompanied with signs of autonomic nervous system involvement. Level of autonomic dysfunction was not the level required for the diagnosis of probable MSA. On initially performed 1.5T MRI, the most prominent neurodegenerative feature of brain stem, cerebellum and basal ganglia was atrophy, however features like "hot-cross bun" sign, "slit-like" putaminal rim and middle cerebellar peduncle hyperintensities were detected only after MR imaging on higher resolution (3T) device. Our case points to the possibility that some typical structural changes that can help in diagnostic process may not be clearly visible on 1.5 T MRI devices. In such cases we suggest using 3T MRI device, if feasible, in order to demonstrate findings that may help in establishing the diagnosis of possible MSA.

  4. Progression of multiple system atrophy (MSA): a prospective natural history study by the European MSA Study Group (EMSA SG).

    PubMed

    Geser, Felix; Wenning, Gregor K; Seppi, Klaus; Stampfer-Kountchev, Michaela; Scherfler, Christoph; Sawires, Martin; Frick, Carolin; Ndayisaba, Jean-Pierre; Ulmer, Hanno; Pellecchia, Maria T; Barone, Paolo; Kim, Hee T; Hooker, Juzar; Quinn, Niall P; Cardozo, Adriana; Tolosa, Eduardo; Abele, Michael; Klockgether, Thomas; Østergaard, Karen; Dupont, Erik; Schimke, Nicole; Eggert, Karla M; Oertel, Wolfgang; Djaldetti, Ruth; Poewe, Werner

    2006-02-01

    The disease-specific Unified Multiple System Atrophy Rating Scale (UMSARS) has been developed recently and validated for assessing disease severity in multiple system atrophy (MSA). Here, we aimed at (1) assessing rates of disease progression in MSA and (2) validating UMSARS for sensitivity to change over time. Impairment was assessed at two time points 12 months apart using UMSARS Part I (historical review), UMSARS Part II (motor examination), as well as measures of global disease severity, including UMSARS Part IV, Hoehn and Yahr (HY) Parkinson's disease staging, Schwab England Activities of Daily Living (SE ADL), and a three-point global Severity Scale (SS3). Fifty patients (male:female ratio, 1:0.9; possible MSA, 16%; probable MSA, 84%; MSA-parkinsonian, 58%; MSA-cerebellar, 42%) were assessed twice with an interval of 12.3 months. UMSARS II scores progressed by 57.3% (P<0.0001) and UMSARS I scores by 35.6% (P<0.0001) in relation to the respective baseline scores with no differences between motor subtypes, diagnostic categories and gender. Significant inverse correlations between (1) UMSARS I or UMSARS II progression and (2) baseline disability measures (i.e., the respective UMSARS or SS3 scores) and disease duration were found. Furthermore, the increases in HY staging, SE ADL and SS3 correlated significantly with UMSARS I, UMSARS II, and UMSARS IV progression. This report is the first prospective study showing rapid annual UMSARS rates of decline in MSA. Our data contribute to the ongoing validation process of UMSARS, and they facilitate the planning and implementation of future neuroprotective intervention trials.

  5. Increased cerebellar activation after repetitive transcranial magnetic stimulation over the primary motor cortex in patients with multiple system atrophy

    PubMed Central

    Li, Linling; Wu, Tianxia; Hou, Bo; Wu, Shuang; Feng, Feng; Cui, Liying

    2016-01-01

    Background Previous review reported that the high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1) of Parkinson’s disease (PD) patients could alleviate their symptoms. This study aimed to investigate the effect of rTMS over the left M1 of patients with multiple system atrophy (MSA). Methods Fifteen MSA patients were randomly assigned to receive a 10-session real (EP: group of experimental patients; n=7) or sham (CP: group of control patients; n=8) rTMS stimulation over two weeks. The overall experimental procedure consisted of two functional magnetic resonance imaging (fMRI) sessions, before and after a 10-session rTMS treatment. A complex self-paced sequential tapping task was performed during fMRI scanning. In addition, 18 age and gender matched healthy controls (HC) were enrolled. Subjects from the HC group did not receive any rTMS treatment and they underwent fMRI examination only once. The primary end point was the motor score change of the Unified Multiple System Atrophy Rating Scale (UMSARS-II) measured before and after the 5th and 10th session. Task-related activation was also compared among groups. Results After active rTMS treatment, only patients of EP group significant improvement in UMSARS-II score. Compared to HC, MSA patients showed significant activation over similar brain areas except for the cerebellum. Increased activation was obtained in the bilateral cerebellum after rTMS treatment in the EP group. On the contrary, no increased activation was identified in the CP group. Conclusions Our results highlight rTMS over M1 induced motor improvement in MSA patients that may be associated with increased activation in the cerebellum. PMID:27127756

  6. Temporal Causal Diagrams for Diagnosing Failures in Cyber Physical Systems

    DTIC Science & Technology

    2014-10-02

    that are designed to detect abnormal changes in physical proper- ties (current, voltage , impedance) and actuation devices such as breakers that can... detects the absence of the discrepancy D3 (transition: D3 ↓)), it issues a command C2 (event) and transitions back to the state S1 (and restores the system ... intelligent process control for cogenerator plants. Journal of Parallel and Distributed Systems , 15, 90–103. Lee, S., Choi, M., Kang, S., Jin, B., Lee, D

  7. Rapid prenatal diagnosis of spinal muscular atrophy by denaturing high-performance liquid chromatography system.

    PubMed

    Shaw, Sheng-Wen; Cheng, Po-Jen; Chang, Shuenn-Dhy; Lin, Yu-Ting; Hung, Chia-Cheng; Chen, Chih-Ping; Su, Yi-Ning

    2008-01-01

    Use of Denaturing High-Performance Liquid Chromatography (DHPLC) in prenatal diagnosis of spinal muscular atrophy (SMA). Thirty-three members of 7 families participated in carrier test and disease detection of SMA. Prenatal genetic diagnosis was performed if both parents were carriers or any family members had SMA. DNA extracted from blood, chorionic villi and amniotic fluid was amplified and used for DHPLC. Twenty SMA carriers, seven SMA affected cases, and six normal individuals were identified. SMA status was demonstrated by genotyping and total copy number determinations of SMN1 and SMN2. Families 1-3 were classified as group one (SMA affecting previously born child). Group two, comprising families 4 and 5, had lost a child due to an unknown muscular disease. Group three (SMA-affected parent) comprised families 6 and 7; carrier testing was done. DHPLC prenatal genetic diagnosis was made in seven pregnancies, one in each family (affected, n=2; carrier, n=3; normal, n=2). Pregnancy was terminated for the two affected fetuses. The others were delivered uneventfully and SMA free. DHPLC prenatal diagnosis of SMA and determination of SMA status in adults is possible, and SMN1 and SMN2 copy numbers can be determined.

  8. Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

    PubMed Central

    Hussain, I; Brady, C; Swinn, M; Mathias, C; Fowler, C

    2001-01-01

    OBJECTIVES—To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy.
METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital.
RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with

  9. Using a Client Team to Diagnose Work Systems.

    ERIC Educational Resources Information Center

    Ombrello, Leon

    1979-01-01

    Explains the use of a trained team selected from an organization to supply knowledge of the work system and help gather and process the data within a reasonable time. Role relationships, diagnostic team activities, team knowledge and skill requirements, team member selection, and costs are discussed. (JD)

  10. Mobile In Vivo Infrared Data Collection and Diagnoses Comparison System

    NASA Technical Reports Server (NTRS)

    Mintz, Frederick W. (Inventor); Moynihan, Philip I. (Inventor); Gunapala, Sarath D. (Inventor)

    2013-01-01

    Described is a mobile in vivo infrared brain scan and analysis system. The system includes a data collection subsystem and a data analysis subsystem. The data collection subsystem is a helmet with a plurality of infrared (IR) thermometer probes. Each of the IR thermometer probes includes an IR photodetector capable of detecting IR radiation generated by evoked potentials within a user's skull. The helmet is formed to collect brain data that is reflective of firing neurons in a mobile subject and transmit the brain data to the data analysis subsystem. The data analysis subsystem is configured to generate and display a three-dimensional image that depicts a location of the firing neurons. The data analysis subsystem is also configured to compare the brain data against a library of brain data to detect an anomaly in the brain data, and notify a user of any detected anomaly in the brain data.

  11. An expert system for diagnosing anomalies of spacecraft

    NASA Technical Reports Server (NTRS)

    Lauriente, Michael; Durand, Rick; Vampola, AL; Koons, Harry C.; Gorney, David

    1994-01-01

    Although the analysis of anomalous behavior of satellites is difficult because it is a very complex process, it is important to be able to make an accurate assessment in a timely manner when the anomaly is observed. Spacecraft operators may have to take corrective action or to 'safe' the spacecraft; space-environment forecasters may have to assess the environmental situation and issue warnings and alerts regarding hazardous conditions, and scientists and engineers may want to gain knowledge for future designs to mitigate the problems. Anomalies can be hardware problems, software errors, environmentally induced, or even the cause of workmanship. Spacecraft anomalies attributable to electrostatic discharges have been known to cause command errors. A goal is to develop an automated system based on this concept to reduce the number of personnel required to operate large programs or missions such as Hubble Space Telescope (HST) and Mission to Planet Earth (MTPE). Although expert systems to detect anomalous behavior of satellites during operations are established, diagnosis of the anomaly is a complex procedure and is a new development.

  12. Postural and action myoclonus in patients with parkinsonian type multiple system atrophy.

    PubMed

    Salazar, G; Valls-Solé, J; Martí, M J; Chang, H; Tolosa, E S

    2000-01-01

    Patients with a parkinsonian syndrome and features of multisystem atrophy (pMSA) may exhibit abnormal movements of the hands and fingers, which are reported in the literature either as "jerky" tremor or myoclonus. We studied clinically and electrophysiologically these movements in 11 consecutive patients with pMSA. No abnormal movements were observed when the patients were at complete rest, except for a characteristic parkinsonian "pill-rolling" tremor in one patient. Abnormal small-amplitude, nonrhythmic movements involving just one or a few fingers, or more rarely the whole hand, were observed in nine patients when holding a posture or at the beginning of an action. Accelerometric recordings showed small-amplitude irregular oscillations which, contrary to those of patients with tremor, had no predominant peak in the Fast Fourier frequency spectrum analysis. Electromyographic recordings in the forearm and hand muscles showed brief jerks of less than 100 ms duration which were synchronous in antagonist muscles of the forearm and alternated with brief periods of silence. Electrical stimulation of the digital nerves evoked consistent reflex responses in the wrist flexor and extensor muscles at a latency of 55.3+/-4.1 ms (range, 50-63 ms). Routine electroencephalographic (EEG) and somatosensory evoked potentials to median nerve stimulation were normal. Back-averaging of the EEG activity time-locked to the jerks was performed in two patients with no evidence of abnormal cortical activity. Two patients had episodes of transient respiratory failure related to pneumonia. This caused a long-lasting enhancement of the abnormal hand and finger movements, which became larger and more widespread, with features of posthypoxic myoclonus. We conclude that the abnormal hand and finger movements of patients with pMSA are a form of postural and action myoclonus, and can be described as mini-polymyoclonus.

  13. Diagnosing and curing system freeze-ups: Part II

    SciTech Connect

    Frey, R.

    1996-02-01

    In our last article, we discussed determination and possible causes leading to frozen pipes in the heating system. We now turn to the matter of dealing with such freeze-ups. There are two major categories of frozen heating systems. The first and worst we can label the {open_quotes}Floridian Flew{close_quotes} type, when the usual occupants have taken off for warmer climates. The second is the {open_quotes}Howcudit {open_quote}B{close_quote} virus,{close_quotes} which occurs to normal people under an unusual Arctic Attack right while they are living there. Regarding the first, I never cease to be amazed how folks can just up and leave their house for three days to three months without making proper arrangements for monitoring the temperature of their home during their absence. There are a frightening number of humanoids out there, who either lack a minimal presence of common sense, or who are terrible gamblers. The amazing thing is that some of these folks wouldn`t even gamble a postage stamp on a magazine sweepstakes, but still will gamble the contents of their home by driving off for two weeks at Disneyland in the middle of January without ever making any provision for assuring that their house doesn`t freeze up while they are away. The {open_quotes}Howcudit {open_quote}B{close_quote}{close_quotes} type is not nearly as devasting as the {open_quotes}Floridian Flew.{close_quotes} Imagine coming home to an icy cold house after flying in from the sunny beaches of some tropical paradise. The oilburner switch is on. The thermostate is set at 60 where we left it, but the needle is buried somewhere down behind the cover, like it is cowering from guilt. {open_quotes}Oh Man! I just checked the bathroom; there is an icicle hanging from the vanity faucet and the toilet bowl is a block of ice.{close_quotes}

  14. Optic nerve atrophy

    MedlinePlus

    Optic atrophy; Optic neuropathy ... There are many causes of optic atrophy. The most common is poor blood flow. This is called ischemic optic neuropathy. The problem most often affects older adults. ...

  15. Spinal muscular atrophy

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000996.htm Spinal muscular atrophy To use the sharing features on this page, please enable JavaScript. Spinal muscular atrophy is a group of disorders of the motor ...

  16. Spinal Muscular Atrophy (SMA)

    MedlinePlus

    ... Habits for TV, Video Games, and the Internet Spinal Muscular Atrophy (SMA) KidsHealth > For Parents > Spinal Muscular Atrophy (SMA) Print ... treatment for the disease's most troubling symptoms. About SMA Normally, healthy nerve cells in the brain called ...

  17. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment

    PubMed Central

    Sintusek, Palittiya; Catapano, Francesco; Angkathunkayul, Napat; Marrosu, Elena; Parson, Simon H.; Morgan, Jennifer E.; Muntoni, Francesco; Zhou, Haiyan

    2016-01-01

    Gastrointestinal (GI) defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA). Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN) protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON) designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome. PMID:27163330

  18. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment.

    PubMed

    Sintusek, Palittiya; Catapano, Francesco; Angkathunkayul, Napat; Marrosu, Elena; Parson, Simon H; Morgan, Jennifer E; Muntoni, Francesco; Zhou, Haiyan

    2016-01-01

    Gastrointestinal (GI) defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA). Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN) protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON) designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome.

  19. Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson's disease and multiple system atrophy.

    PubMed

    Klos, Kevin J; Bower, James H; Josephs, Keith A; Matsumoto, Joseph Y; Ahlskog, J Eric

    2005-09-01

    Pathological hypersexuality developed in 13 patients with PD and two patients ultimately diagnosed clinically with MSA. Hypersexuality began within 8 months after starting dopamine agonist therapy in 14 of 15 cases, including four on agonist monotherapy. It resolved in the four cases where the agonist was stopped, despite continued levodopa therapy. This was not an isolated behavioral problem in most, with additional compulsive or addictive behaviors coinciding in nine patients (60%). A systematic literature review of pathological hypersexuality in PD revealed similar medication histories; combining these cases with our series, 26 of 29 patients (90%) were on adjuvant dopamine agonists.

  20. Sequential Window Diagnoser for Discrete-Event Systems Under Unreliable Observations

    SciTech Connect

    Wen-Chiao Lin; Humberto E. Garcia; David Thorsley; Tae-Sic Yoo

    2009-09-01

    This paper addresses the issue of counting the occurrence of special events in the framework of partiallyobserved discrete-event dynamical systems (DEDS). Developed diagnosers referred to as sequential window diagnosers (SWDs) utilize the stochastic diagnoser probability transition matrices developed in [9] along with a resetting mechanism that allows on-line monitoring of special event occurrences. To illustrate their performance, the SWDs are applied to detect and count the occurrence of special events in a particular DEDS. Results show that SWDs are able to accurately track the number of times special events occur.

  1. Vaginal Atrophy

    MedlinePlus

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... PHD Additional Resources Menopause Map Mayo Clinic The endocrine system is a network of glands and organs that ...

  2. Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy.

    PubMed

    Milan, Giulia; Romanello, Vanina; Pescatore, Francesca; Armani, Andrea; Paik, Ji-Hye; Frasson, Laura; Seydel, Anke; Zhao, Jinghui; Abraham, Reimar; Goldberg, Alfred L; Blaauw, Bert; DePinho, Ronald A; Sandri, Marco

    2015-04-10

    Stresses like low nutrients, systemic inflammation, cancer or infections provoke a catabolic state characterized by enhanced muscle proteolysis and amino acid release to sustain liver gluconeogenesis and tissue protein synthesis. These conditions activate the family of Forkhead Box (Fox) O transcription factors. Here we report that muscle-specific deletion of FoxO members protects from muscle loss as a result of the role of FoxOs in the induction of autophagy-lysosome and ubiquitin-proteasome systems. Notably, in the setting of low nutrient signalling, we demonstrate that FoxOs are required for Akt activity but not for mTOR signalling. FoxOs control several stress-response pathways such as the unfolded protein response, ROS detoxification, DNA repair and translation. Finally, we identify FoxO-dependent ubiquitin ligases including MUSA1 and a previously uncharacterised ligase termed SMART (Specific of Muscle Atrophy and Regulated by Transcription). Our findings underscore the central function of FoxOs in coordinating a variety of stress-response genes during catabolic conditions.

  3. A Type-2 Fuzzy Image Processing Expert System for Diagnosing Brain Tumors.

    PubMed

    Zarinbal, M; Fazel Zarandi, M H; Turksen, I B; Izadi, M

    2015-10-01

    The focus of this paper is diagnosing and differentiating Astrocytomas in MRI scans by developing an interval Type-2 fuzzy automated tumor detection system. This system consists of three modules: working memory, knowledge base, and inference engine. An image processing method with three steps of preprocessing, segmentation and feature extraction, and approximate reasoning is used in inference engine module to enhance the quality of MRI scans, segment them into desired regions, extract the required features, and finally diagnose and differentiate Astrocytomas. However, brain tumors have different characteristics in different planes, so considering one plane of patient's MRI scan may cause inaccurate results. Therefore, in the developed system, several consecutive planes are processed. The performance of this system is evaluated using 95 MRI scans and the results show good improvement in diagnosing and differentiating Astrocytomas.

  4. Multiple system atrophy of the cerebellar type (MSA-C) with concomitant beta-amyloid and tau pathology.

    PubMed

    Bujan, Bartosz; Hofer, Markus J; Oertel, Wolfgang H; Pagenstecher, Axel; Bürk, Katrin

    2013-01-01

    Multiple system atrophy (MSA) is a rapidly progressive sporadic α-synucleinopathy with adult onset characterized by progressive cerebellar ataxia, basal ganglia symptoms, autonomic dysfunction and pyramidal tract signs. While full-blown dementia is considered an exclusion criterion according to Consensus Guidelines, mild cognitive deficits such as fronto-executive dysfunction have been reported in some MSA individuals. However, the underlying anatomic correlate still has to be elucidated. We here report a 74-year-old patient with a clinical diagnosis of "probable MSA of the cerebellar type (MSA-C)" who developed pronounced clinical symptoms of fronto-executive dysfunction. Neuropathologic investigations revealed (1) numerous glial cytoplasmic inclusions (GCI) in the putamen, mesencephalon and cerebellum, (2) pronounced betaamyloid pathology in the frontal lobe and (3) mild hippocampal τ-pathology. In this patient, fronto-executive dysfunction can easily be explained by frontal degeneration typical for AD. These findings challenge the concept of cognitive dysfunction as a core feature of MSA as long as concomitant pathology other than MSA has not been reliably excluded by post mortem analysis.

  5. The Economic Costs of Progressive Supranuclear Palsy and Multiple System Atrophy in France, Germany and the United Kingdom

    PubMed Central

    McCrone, Paul; Payan, Christine Anne Mary; Knapp, Martin; Ludolph, Albert; Agid, Yves; Leigh, P. Nigel; Bensimon, Gilbert

    2011-01-01

    Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are progressive disabling neurological conditions usually fatal within 10 years of onset. Little is known about the economic costs of these conditions. This paper reports service use and costs from France, Germany and the UK and identifies patient characteristics that are associated with cost. 767 patients were recruited, and 760 included in the study, from 44 centres as part of the NNIPPS trial. Service use during the previous six months was measured at entry to the study and costs calculated. Mean six-month costs were calculated for 742 patients. Data on patient sociodemographic and clinical characteristics were recorded and used in regression models to identify predictors of service costs and unpaid care costs (i.e., care from family and friends). The mean six-month service costs of PSP were €24,491 in France, €30,643 in Germany and €25,655 in the UK. The costs for MSA were €28,924, €25,645 and €19,103 respectively. Unpaid care accounted for 68–76%. Formal and unpaid costs were significantly higher the more severe the illness, as indicated by the Parkinson's Plus Symptom scale. There was a significant inverse relationship between service and unpaid care costs. PMID:21931694

  6. Muscle expression of mutant androgen receptor accounts for systemic and motor neuron disease phenotypes in spinal and bulbar muscular atrophy.

    PubMed

    Cortes, Constanza J; Ling, Shuo-Chien; Guo, Ling T; Hung, Gene; Tsunemi, Taiji; Ly, Linda; Tokunaga, Seiya; Lopez, Edith; Sopher, Bryce L; Bennett, C Frank; Shelton, G Diane; Cleveland, Don W; La Spada, Albert R

    2014-04-16

    X-linked spinal and bulbar muscular atrophy (SBMA) is characterized by adult-onset muscle weakness and lower motor neuron degeneration. SBMA is caused by CAG-polyglutamine (polyQ) repeat expansions in the androgen receptor (AR) gene. Pathological findings include motor neuron loss, with polyQ-AR accumulation in intranuclear inclusions. SBMA patients exhibit myopathic features, suggesting a role for muscle in disease pathogenesis. To determine the contribution of muscle, we developed a BAC mouse model featuring a floxed first exon to permit cell-type-specific excision of human AR121Q. BAC fxAR121 mice develop systemic and neuromuscular phenotypes, including shortened survival. After validating termination of AR121 expression and full rescue with ubiquitous Cre, we crossed BAC fxAR121 mice with Human Skeletal Actin-Cre mice. Muscle-specific excision prevented weight loss, motor phenotypes, muscle pathology, and motor neuronopathy and dramatically extended survival. Our results reveal a crucial role for muscle expression of polyQ-AR in SBMA and suggest muscle-directed therapies as effective treatments.

  7. Systems Biology Investigation of cAMP Modulation to Increase SMN Levels for the Treatment of Spinal Muscular Atrophy

    PubMed Central

    Mack, Sean G.; Cook, Daniel J.; Dhurjati, Prasad; Butchbach, Matthew E. R.

    2014-01-01

    Spinal muscular atrophy (SMA), a leading genetic cause of infant death worldwide, is an autosomal recessive disorder caused by the loss of SMN1 (survival motor neuron 1), which encodes the protein SMN. The loss of SMN1 causes a deficiency in SMN protein levels leading to motor neuron cell death in the anterior horn of the spinal cord. SMN2, however, can also produce some functional SMN to partially compensate for loss of SMN1 in SMA suggesting increasing transcription of SMN2 as a potential therapy to treat patients with SMA. A cAMP response element was identified on the SMN2 promoter, implicating cAMP activation as a step in the transcription of SMN2. Therefore, we investigated the effects of modulating the cAMP signaling cascade on SMN production in vitro and in silico. SMA patient fibroblasts were treated with the cAMP signaling modulators rolipram, salbutamol, dbcAMP, epinephrine and forskolin. All of the modulators tested were able to increase gem formation, a marker for SMN protein in the nucleus, in a dose-dependent manner. We then derived two possible mathematical models simulating the regulation of SMN2 expression by cAMP signaling. Both models fit well with our experimental data. In silico treatment of SMA fibroblasts simultaneously with two different cAMP modulators resulted in an additive increase in gem formation. This study shows how a systems biology approach can be used to develop potential therapeutic targets for treating SMA. PMID:25514431

  8. Distinguishing spinocerebellar ataxia with pure cerebellar manifestation from multiple system atrophy (MSA-C) through saccade profiles.

    PubMed

    Terao, Yasuo; Fukuda, Hideki; Tokushige, Shin-Ichi; Inomata-Terada, Satomi; Yugeta, Akihiro; Hamada, Masashi; Ugawa, Yoshikazu

    2017-01-01

    Patients with spinocerebellar ataxia with pure cerebellar presentation (SCD) and multiple system atrophy (MSA-C) show similar symptoms at early stages, although cerebellofugal pathology predominates in SCD, and cerebellopetal pathology in MSA-C. We studied whether saccade velocity profiles, which reflect the accelerating and braking functions of the cerebellum, can differentiate these two disorders. We recorded visually guided (VGS) and memory guided saccades (MGS) in 29 MSA-C patients, 12 SCD patients, and 92 age-matched normal subjects, and compared their amplitude, peak velocity and duration (accelerating and decelerating phases). Hypometria predominated in VGS and MGS of MSA-C, whereas hypometria was less marked in SCD, with hypermetria frequently noted in MGS. Peak velocity was reduced, and deteriorated with advancing disease both in SCD and MSA-C groups at smaller target eccentricities. The deceleration phase was prolonged in SCD compared to MSA-C and normal groups at larger target eccentricities, which deteriorated with advancing disease. Saccades in MSA-C were characterized by a more prominent acceleration deficit and those in SCD by a more prominent braking defect, possibly caused by the cerebellopetal and cerebellofugal pathologies, respectively. Saccade profiles provide important information regarding the accelerating and braking signals of the cerebellum in spinocerebellar ataxia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Distinct Parameters in the EEG of the PLP α-SYN Mouse Model for Multiple System Atrophy Reinforce Face Validity

    PubMed Central

    Härtner, Lorenz; Keil, Tobias W. M.; Kreuzer, Matthias; Fritz, Eva Maria; Wenning, Gregor K.; Stefanova, Nadia; Fenzl, Thomas

    2017-01-01

    Multiple system atrophy (MSA) is a neurodegenerative movement disorder characterized by parkinsonian symptoms and cerebellar symptoms. Sleep disturbances also play a crucial role in MSA. One of the most convincing animal models in MSA research is the PLP α-SYN model, but to date no studies on sleep disturbances in this mouse model, frequently found in MSA patients are available. We identified spectral shifts within the EEG of the model, strikingly resembling results of clinical studies. We also characterized muscle activity during REM sleep, which is one of the key symptoms in REM sleep behavioral disorder. Spectral shifts and REM sleep-linked muscle activity were age dependent, supporting Face Validity of the PLP α-SYN model. We also strongly suggest our findings to be critically evaluated for Predictive Validity in future studies. Currently, research on MSA lacks potential compounds attenuating or curing MSA. Future drugs must prove its potential in animal models, for this our study provides potential biomarkers. PMID:28119583

  10. Effect of Repetitive Transcranial Magnetic Stimulation on fMRI Resting-State Connectivity in Multiple System Atrophy

    PubMed Central

    Chou, Ying-hui; Zhao, Yan-Ping; Hou, Bo; Feng, Feng

    2015-01-01

    Abstract Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been used to treat neurological and psychiatric conditions. Although results of rTMS intervention are promising, so far, little is known about the rTMS effect on brain functional networks in clinical populations. In this study, we used a whole-brain connectivity analysis of resting-state functional magnetic resonance imaging data to uncover changes in functional connectivity following rTMS intervention and their association with motor symptoms in patients with multiple system atrophy (MSA). Patients were randomized to active rTMS or sham rTMS groups and completed a 10-session 5-Hz rTMS treatment over the left primary motor area. The results showed significant rTMS-related changes in motor symptoms and functional connectivity. Specifically, (1) significant improvement of motor symptoms was observed in the active rTMS group, but not in the sham rTMS group; and (2) several functional links involving the default mode, cerebellar, and limbic networks exhibited positive changes in functional connectivity in the active rTMS group. Moreover, the positive changes in functional connectivity were associated with improvement in motor symptoms for the active rTMS group. The present findings suggest that rTMS may improve motor symptoms by modulating functional links connecting to the default mode, cerebellar, and limbic networks, inferring a future therapeutic candidate for patients with MSA. PMID:25786196

  11. Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy.

    PubMed

    Shabanpoor, Fazel; Hammond, Suzan M; Abendroth, Frank; Hazell, Gareth; Wood, Matthew J A; Gait, Michael J

    2017-06-01

    Splice-switching antisense oligonucleotides are emerging treatments for neuromuscular diseases, with several splice-switching oligonucleotides (SSOs) currently undergoing clinical trials such as for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). However, the development of systemically delivered antisense therapeutics has been hampered by poor tissue penetration and cellular uptake, including crossing of the blood-brain barrier (BBB) to reach targets in the central nervous system (CNS). For SMA application, we have investigated the ability of various BBB-crossing peptides for CNS delivery of a splice-switching phosphorodiamidate morpholino oligonucleotide (PMO) targeting survival motor neuron 2 (SMN2) exon 7 inclusion. We identified a branched derivative of the well-known ApoE (141-150) peptide, which as a PMO conjugate was capable of exon inclusion in the CNS following systemic administration, leading to an increase in the level of full-length SMN2 transcript. Treatment of newborn SMA mice with this peptide-PMO (P-PMO) conjugate resulted in a significant increase in the average lifespan and gains in weight, muscle strength, and righting reflexes. Systemic treatment of adult SMA mice with this newly identified P-PMO also resulted in small but significant increases in the levels of SMN2 pre-messenger RNA (mRNA) exon inclusion in the CNS and peripheral tissues. This work provides proof of principle for the ability to select new peptide paradigms to enhance CNS delivery and activity of a PMO SSO through use of a peptide-based delivery platform for the treatment of SMA potentially extending to other neuromuscular and neurodegenerative diseases.

  12. Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy

    PubMed Central

    Shabanpoor, Fazel; Hammond, Suzan M; Abendroth, Frank; Hazell, Gareth; Wood, Matthew J.A.

    2017-01-01

    Splice-switching antisense oligonucleotides are emerging treatments for neuromuscular diseases, with several splice-switching oligonucleotides (SSOs) currently undergoing clinical trials such as for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). However, the development of systemically delivered antisense therapeutics has been hampered by poor tissue penetration and cellular uptake, including crossing of the blood–brain barrier (BBB) to reach targets in the central nervous system (CNS). For SMA application, we have investigated the ability of various BBB-crossing peptides for CNS delivery of a splice-switching phosphorodiamidate morpholino oligonucleotide (PMO) targeting survival motor neuron 2 (SMN2) exon 7 inclusion. We identified a branched derivative of the well-known ApoE (141–150) peptide, which as a PMO conjugate was capable of exon inclusion in the CNS following systemic administration, leading to an increase in the level of full-length SMN2 transcript. Treatment of newborn SMA mice with this peptide-PMO (P-PMO) conjugate resulted in a significant increase in the average lifespan and gains in weight, muscle strength, and righting reflexes. Systemic treatment of adult SMA mice with this newly identified P-PMO also resulted in small but significant increases in the levels of SMN2 pre-messenger RNA (mRNA) exon inclusion in the CNS and peripheral tissues. This work provides proof of principle for the ability to select new peptide paradigms to enhance CNS delivery and activity of a PMO SSO through use of a peptide-based delivery platform for the treatment of SMA potentially extending to other neuromuscular and neurodegenerative diseases. PMID:28118087

  13. Spinal muscular atrophy with respiratory distress type 1 (SMARD1).

    PubMed

    Kaindl, Angela M; Guenther, Ulf-Peter; Rudnik-Schöneborn, Sabine; Varon, Raymonda; Zerres, Klaus; Schuelke, Markus; Hübner, Christoph; von Au, Katja

    2008-02-01

    Autosomal recessive spinal muscular atrophy with respiratory distress type 1 (SMARD1), recently referred to as distal spinal muscular atrophy 1 (DSMA1; MIM#604320) and also known as distal hereditary motor neuropathy type 6 (dHMN6 or HMN6), results from mutations in the IGHMBP2 gene on chromosome 11q13.3 encoding the immunoglobulin micro-binding protein 2. In contrast to the infantile spinal muscular atrophy type 1 (SMA1; Werdnig-Hoffmann disease) with weakness predominantly of proximal muscles and bell-shaped thorax deformities due to intercostal muscle atrophy, infants with distal spinal muscular atrophy 1 usually present with distal muscle weakness, foot deformities, and sudden respiratory failure due to diaphragmatic paralysis that often requires urgent intubation. In this article, the authors review the clinical, neuropathological, and genetic aspects of distal spinal muscular atrophy 1 and discuss differential diagnoses.

  14. Is multiple system atrophy with cerebellar ataxia (MSA-C) like spinocerebellar ataxia and multiple system atrophy with parkinsonism (MSA-P) like Parkinson's disease? - A saccade study on pathophysiology.

    PubMed

    Terao, Yasuo; Fukuda, Hideki; Tokushige, Shinnichi; Inomata-Terada, Satomi; Yugeta, Akihiro; Hamada, Masashi; Ichikawa, Yaeko; Hanajima, Ritsuko; Ugawa, Yoshikazu

    2016-02-01

    Patients with multiple system atrophy (MSA) are classified into those mainly manifesting cerebellar ataxia (MSA-C) and those mainly manifesting parkinsonism (MSA-P). Pathophysiological bases of these subtypes remain unclear. We hypothesized that MSA-C patients would resemble spinocerebellar degeneration patients and MSA-P patients would resemble Parkinson's disease (PD) patients in saccade abnormalities. We recorded visually guided and memory guided saccades (MGS) in 27 MSA-C and 15 MSA-P patients, as well as 50 age-matched normal subjects, 14 spinocerebellar degeneration patients showing pure cerebellar symptoms (SCD) and 61 Parkinson's disease (PD) patients. Saccade parameters of both tasks showed similar changes with progressing disease in SCD and MSA-C patients, as did those of MSA-C and MSA-P patients, although hypometria was slightly more pronounced in MSA-P. In both subtypes of MSA, latency and success rate of MGS were stable throughout disease stages, whereas they deteriorated progressively with progressing disease in PD. Pathophysiology underlying MSA-C and MSA-P is similar as viewed from saccade performance. The MGS performance in MSA was preserved. However, MSA-P patients showed more marked hypometria, suggesting a mixture of basal ganglia pathophysiology. The similarity of saccade performance between MSA-C and MSA-P may reflect common olivopontocerebellar pathology, while the direct pathway of the basal ganglia is relatively spared compared with PD, even in MSA-P. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. A second generation expert system for checking and diagnosing AXAF's electric power system

    NASA Astrophysics Data System (ADS)

    Bykat, Alex

    1992-12-01

    AXAF - Advanced X-ray Astrophysics Facility - is a third NASA's great space observatory. Each of these observatories is intended to cover different parts of the electromagnetic spectrum (x-ray for AXAF) and to provide high resolution images of celestial sources in our universe. While the spacecraft is in orbit, the electric power system (EPS) performance is monitored via sensors measuring voltages, currents, pressures, and temperatures. The sensor data are sent from the spacecraft to the ground station as telemetry and analyzed on arrival. Monitoring, diagnosis and maintenance of such EPS is an arduous task which requires expertise and constant attention of the ground personnel. To help the ground crew in this task, much of it should be automated and delegated to expert systems, which draw engineer's attention to possible malfunctions and allows him to review the telemetry to determine the source of the trouble, diagnose the suspected fault and to propose a corrective action. Those systems are built on assumptions such as: (1) domain knowledge is available and can be represented as a set of rules; (2) domain knowledge is circumscribed, static, and monotonic; and (3) expert decision making can be emulated by a logical inference mechanism.

  16. A second generation expert system for checking and diagnosing AXAF's electric power system

    NASA Technical Reports Server (NTRS)

    Bykat, Alex

    1992-01-01

    AXAF - Advanced X-ray Astrophysics Facility - is a third NASA's great space observatory. Each of these observatories is intended to cover different parts of the electromagnetic spectrum (x-ray for AXAF) and to provide high resolution images of celestial sources in our universe. While the spacecraft is in orbit, the electric power system (EPS) performance is monitored via sensors measuring voltages, currents, pressures, and temperatures. The sensor data are sent from the spacecraft to the ground station as telemetry and analyzed on arrival. Monitoring, diagnosis and maintenance of such EPS is an arduous task which requires expertise and constant attention of the ground personnel. To help the ground crew in this task, much of it should be automated and delegated to expert systems, which draw engineer's attention to possible malfunctions and allows him to review the telemetry to determine the source of the trouble, diagnose the suspected fault and to propose a corrective action. Those systems are built on assumptions such as: (1) domain knowledge is available and can be represented as a set of rules; (2) domain knowledge is circumscribed, static, and monotonic; and (3) expert decision making can be emulated by a logical inference mechanism.

  17. Diagnosing tuberculosis with a novel support vector machine-based artificial immune recognition system.

    PubMed

    Saybani, Mahmoud Reza; Shamshirband, Shahaboddin; Golzari Hormozi, Shahram; Wah, Teh Ying; Aghabozorgi, Saeed; Pourhoseingholi, Mohamad Amin; Olariu, Teodora

    2015-04-01

    Tuberculosis (TB) is a major global health problem, which has been ranked as the second leading cause of death from an infectious disease worldwide. Diagnosis based on cultured specimens is the reference standard, however results take weeks to process. Scientists are looking for early detection strategies, which remain the cornerstone of tuberculosis control. Consequently there is a need to develop an expert system that helps medical professionals to accurately and quickly diagnose the disease. Artificial Immune Recognition System (AIRS) has been used successfully for diagnosing various diseases. However, little effort has been undertaken to improve its classification accuracy. In order to increase the classification accuracy of AIRS, this study introduces a new hybrid system that incorporates a support vector machine into AIRS for diagnosing tuberculosis. Patient epacris reports obtained from the Pasteur laboratory of Iran were used as the benchmark data set, with the sample size of 175 (114 positive samples for TB and 60 samples in the negative group). The strategy of this study was to ensure representativeness, thus it was important to have an adequate number of instances for both TB and non-TB cases. The classification performance was measured through 10-fold cross-validation, Root Mean Squared Error (RMSE), sensitivity and specificity, Youden's Index, and Area Under the Curve (AUC). Statistical analysis was done using the Waikato Environment for Knowledge Analysis (WEKA), a machine learning program for windows. With an accuracy of 100%, sensitivity of 100%, specificity of 100%, Youden's Index of 1, Area Under the Curve of 1, and RMSE of 0, the proposed method was able to successfully classify tuberculosis patients. There have been many researches that aimed at diagnosing tuberculosis faster and more accurately. Our results described a model for diagnosing tuberculosis with 100% sensitivity and 100% specificity. This model can be used as an additional tool for

  18. On the diagnosability of multicomputer systems with homogeneous and incomplete tests

    SciTech Connect

    Krawczyk, H.; Kozlowski, W.E. )

    1988-11-01

    A generalized PMC model, where only a subset of possible unit faults (the same for each unit) can be detected by unit tests, is considered. A category of visible faults is introduced and the necessary and sufficient condition for the new class of tupsilon-diagnosable system is determined. Moreover, an O(absolute value T ) diagnosis algorithm is presented.

  19. Diagnoses and Presenting Symptoms in an Infant Psychiatry Clinic: Comparison of Two Diagnostic Systems.

    ERIC Educational Resources Information Center

    Frankel, Karen A.; Boyum, Lisa A.; Harmon, Robert J.

    2004-01-01

    Objective: To present data from a general infant psychiatry clinic, including range and frequency of presenting symptoms, relationship between symptoms and diagnoses, and comparison of two diagnostic systems, DSM-IV and Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC: 0-3). Method: A…

  20. Diagnoses and Presenting Symptoms in an Infant Psychiatry Clinic: Comparison of Two Diagnostic Systems.

    ERIC Educational Resources Information Center

    Frankel, Karen A.; Boyum, Lisa A.; Harmon, Robert J.

    2004-01-01

    Objective: To present data from a general infant psychiatry clinic, including range and frequency of presenting symptoms, relationship between symptoms and diagnoses, and comparison of two diagnostic systems, DSM-IV and Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC: 0-3). Method: A…

  1. Development and Evaluation of an Expert System for Diagnosing Pest Damage of Red Pine

    Treesearch

    Daniel L Schmoldt; George L. Martin

    1989-01-01

    An expert system for diagnosing pest damage of red pine stands in Wisconsin, PREDICT, runs on IBM or compatible microcomputers and is designed to be useful for field foresters with no advanced training in forest pathology or entomology. PREDICT recognizes 28 damaging agents including species of mammals, insects, and pathogens, as well as two types of abiotic damage....

  2. Tracking sensory system atrophy and outcome prediction in spinal cord injury

    PubMed Central

    Grabher, Patrick; Callaghan, Martina F.; Ashburner, John; Weiskopf, Nikolaus; Thompson, Alan J.; Curt, Armin

    2015-01-01

    Objective In patients with subacute spinal cord injury (SCI), the motor system undergoes progressive structural changes rostral to the lesion, which are associated with motor outcome. The extent to which the sensory system is affected and how this relates to sensory outcome are uncertain. Methods Changes in the sensory system were prospectively followed by applying a comprehensive magnetic resonance imaging (MRI) protocol to 14 patients with subacute traumatic SCI at baseline, 2 months, 6 months, and 12 months after injury, combined with a full neurological examination and comprehensive pain assessment. Eighteen controls underwent the same MRI protocol. T1‐weighted volumes, myelin‐sensitive magnetization transfer saturation (MT), and longitudinal relaxation rate (R1) mapping provided data on spinal cord and brain morphometry and microstructure. Regression analysis assessed the relationship between MRI readouts and sensory outcomes. Results At 12 months from baseline, sensory scores were unchanged and below‐level neuropathic pain became prominent. Compared with controls, patients showed progressive degenerative changes in cervical cord and brain morphometry across the sensory system. At 12 months, MT and R1 were reduced in areas of structural decline. Sensory scores at 12 months correlated with rate of change in cord area and brain volume and decreased MT in the spinal cord at 12 months. Interpretation This study has demonstrated progressive atrophic and microstructural changes across the sensory system with a close relation to sensory outcome. Structural MRI protocols remote from the site of lesion provide new insights into neuronal degeneration underpinning sensory disturbance and have potential as responsive biomarkers of rehabilitation and treatment interventions. Ann Neurol 2015;78:Ann Neurol 2015;78:679–696 PMID:26290444

  3. The evolution of shortcomings in Incident Command System: Revisions have allowed critical management functions to atrophy.

    PubMed

    Stambler, Kimberly S; Barbera, Joseph A

    2015-01-01

    The original Incident Command System (ICS) was created through the federally funded Firefighting Resources of Southern California Organized for Potential Emergencies (FIRESCOPE) program. Initially developed as one element of multiagency coordination for managing severe wildfires, the FIRESCOPE ICS guidance was adopted and evolved through increasingly routine wildl and firefighting. It then was modified for all hazards for the fire service. Only later, through the National Incident Management System (NIMS), was ICS officially adopted for all hazards and all responders. Over this multidecade evolution, the current NIMS ICS version became simplified in several key areas compared to the original, robust FIRESCOPE ICS. NIMS ICS is now promulgated as guidance for managing today's novel, complex, and lengthy disasters involving multidisciplinary response but experiences recurrent problems in key functions. This article examines the history of the subtle, yet critical differences in current ICS compared to the original system design, and focuses on information dissemination and intermediate, long-range and contingency planning. ICS transitions resulted in simplification and consolidation of positions and functions, without recognizing and maintaining critical position tasks necessary for managing complex, extended incidents.

  4. Whole body and cardiac metaiodobenzylguanidine kinetics in Parkinson disease and multiple system atrophy: implications for the diagnostic role of imaging.

    PubMed

    Marini, Cecilia; Bandettini di Poggio, Monica; Pomposelli, Elena; Marchese, Roberta; Nobili, Flavio; Morbelli, Silvia D; Villa, Giuseppe; Abbruzzese, Giovanni; Sambuceti, Gianmario

    2010-05-01

    This study investigates whether combined analysis of I-123 metaiodobenzylguanidine (MIBG) kinetics in the heart and in the whole body can improve the accuracy of differential diagnosis between idiopathic Parkinson disease (PD) and a Parkinson variant of multiple system atrophy (MSA-P). A total of 30 patients with clinical suspicion of PD (n = 16) or MSA-P (n = 14) underwent MIBG whole-body planar imaging. Final diagnosis was confirmed at follow-up. Images were collected 30 minutes and 4 hours after tracer injection. Myocardial uptake was evaluated by measuring heart/mediastinum (H/M) ratio and the percent fraction of the injected dose retained by the heart (calculated by whole-body counts). Tracer washout was measured from both the heart and the whole body. H/M ratio was lower in PD than in MSA-P at early imaging (1.32 +/- 0.21 vs. 1.81 +/- 0.46, respectively, P < 0.01), although a large overlap in individual data was observed. By contrast, % of injected dose taken up by the heart documented a large difference between PD and MSA-P (0.97% +/- 0.51% vs. 1.91% +/- 0.66% of the dose, P < 0.01), and a very small overlap in individual values. There was no difference in the heart washout between the 2 Groups (31% +/- 13% vs. 32% +/- 15%, P = 0.9), while tracer loss from the whole body was higher in PD than in MSA-P (29% +/- 12% vs. 19% +/- 10%, P < 0.01). PD and its correlated global postganglionic dysfunction alter MIBG kinetics in the heart and in the whole body. Image analysis accounting for tracer kinetics in the whole body may improve the diagnostic accuracy of this test in patients with suspected PD or MSA-P.

  5. A ground-based comparison of the Muscle Atrophy Research and Exercise System (MARES) and a commercially available isokinetic dynamometer

    NASA Astrophysics Data System (ADS)

    English, Kirk L.; Hackney, Kyle J.; De Witt, John K.; Ploutz-Snyder, Robert J.; Goetchius, Elizabeth L.; Ploutz-Snyder, Lori L.

    2013-11-01

    IntroductionInternational Space Station (ISS) crewmembers perform muscle strength and endurance testing pre- and postflight to assess the physiologic adaptations associated with long-duration exposure to microgravity. However, a reliable and standardized method to document strength changes in-flight has not been established. To address this issue, a proprietary dynamometer, the Muscle Atrophy Research and Exercise System (MARES) has been developed and flown aboard the ISS. The aims of this ground-based investigation were to: (1) evaluate the test-retest reliability of MARES and (2) determine its agreement with a commercially available isokinetic dynamometer previously used for pre- and postflight medical testing. MethodsSix males (179.5±4.7 cm; 82.0±8.7 kg; 31.3±4.0 yr) and four females (163.2±7.3 cm; 63.2±1.9 kg; 32.3±6.8 yr) completed two testing sessions on a HUMAC NORM isokinetic dynamometer (NORM) and two sessions on MARES using a randomized, counterbalanced, cross-over design. Peak torque values at 60° and 180° s-1 were calculated from five maximal repetitions of knee extension (KE) and knee flexion (KF) for each session. Total work at 180° s-1 was determined from the area under the torque versus displacement curve during 20 maximal repetitions of KE and KF. ResultsIntraclass correlation coefficients were relatively high for both devices (0.90-0.99). Only one dependent measure, KE peak torque at 60° s-1 exhibited good concordance between devices (ρ=0.92) and a small average difference (0.9±17.3 N m). ConclusionMARES demonstrated acceptable test-retest reliability and thus should serve as a good tool to monitor in-flight strength changes. However, due to poor agreement with NORM, it is not advisable to compare absolute values obtained on these devices.

  6. Antidepressants reduce neuroinflammatory responses and astroglial alpha-synuclein accumulation in a transgenic mouse model of multiple system atrophy.

    PubMed

    Valera, Elvira; Ubhi, Kiren; Mante, Michael; Rockenstein, Edward; Masliah, Eliezer

    2014-02-01

    Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the pathological accumulation of alpha-synuclein (α-syn) within oligodendroglial cells. This accumulation is accompanied by neuroinflammation with astrogliosis and microgliosis, that leads to neuronal death and subsequent parkinsonism and dysautonomia. Antidepressants have been explored as neuroprotective agents as they normalize neurotrophic factor levels, increase neurogenesis and reduce neurodegeneration, but their anti-inflammatory properties have not been fully characterized. We analyzed the anti-inflammatory profiles of three different antidepressants (fluoxetine, olanzapine and amitriptyline) in the MBP1-hα-syn transgenic (tg) mouse model of MSA. We observed that antidepressant treatment decreased the number of α-syn-positive cells in the basal ganglia of 11-month-old tg animals. This reduction was accompanied with a similar decrease in the colocalization of α-syn with astrocyte markers in this brain structure. Consistent with these results, antidepressants reduced astrogliosis in the hippocampus and basal ganglia of the MBP1-hα-syn tg mice, and modulated the expression levels of key cytokines that were dysregulated in the tg mouse model, such as IL-1β. In vitro experiments in the astroglial cell line C6 confirmed that antidepressants inhibited NF-κB translocation to the nucleus and reduced IL-1β protein levels. We conclude that the anti-inflammatory properties of antidepressants in the MBP1-hα-syn tg mouse model of MSA might be related to their ability to inhibit α-syn propagation from oligodendrocytes to astroglia and to regulate transcription factors involved in cytokine expression. Our results suggest that antidepressants might be of interest as anti-inflammatory and α-syn-reducing agents for MSA and other α-synucleinopathies. Copyright © 2013 Wiley Periodicals, Inc.

  7. Serum creatinine is associated with the prevalence but not disease progression of multiple system atrophy in Chinese population.

    PubMed

    Cao, Bei; Guo, XiaoYan; Chen, Ke; Song, Wei; Huang, Rui; Wei, QianQian; Zhao, Bi; Shang, Hui-Fang

    2016-03-01

    Oxidative stress is involved in the pathogenesis of multiple system atrophy (MSA). Creatine, which is converted to creatinine, has an anti-oxidative effect. Our aim is to clarify the correlations between creatinine and the occurrence as well as the progression of MSA. A total of 115 patients with probable MSA and 115 age- and gender-matched healthy controls were included in the study. The serum creatinine level of all patients and controls were evaluated and compared. The mean age of MSA patients was 58.18 ± 8.67 years and the mean disease duration was 2.85 ± 1.71 years. The creatinine level of MSA patients was significantly lower than that of healthy controls (P < 0.0001). The occurrence of MSA was decreased in the highest creatinine quartiles compared with the lowest creatinine quartiles. In a gender-specific analysis, patients with the highest quartiles and second quartiles of creatinine level had decreased occurrence than patients with the lowest quartile in females, but not in males. The serum level of creatinine was not found correlated with the mean rate of annualised changes, neither with other independent factors, such as age, body mass index (BMI), sex, Unified MSA Rating Scale (UMSARS) scores and disease duration at the initial visit in patients with MSA. High level of serum creatinine may be associated with a low occurrence of MSA in Chinese population, especially in female. However, serum creatinine does not deteriorate or ameliorate the progression of MSA.

  8. Subgroup differences in 'brain-type' transferrin and α-synuclein in Parkinson's disease and multiple system atrophy.

    PubMed

    Yoshihara, Akioh; Fukatsu, Masahiko; Hoshi, Kyoka; Ito, Hiromi; Nollet, Kenneth; Yamaguchi, Yoshiki; Ishii, Ryotaro; Tokuda, Takahiko; Miyajima, Masakazu; Arai, Hajime; Kato, Takeo; Furukawa, Katsutoshi; Arai, Hiroyuki; Kikuchi, Akio; Takeda, Atsushi; Ugawa, Yoshikazu; Hashimoto, Yasuhiro

    2016-08-01

    Two transferrin (Tf) glycan-isoforms were previously found in cerebrospinal fluid (CSF); one appears to be derived from serum (Tf-2) and the other from choroid plexus, a CSF-producing tissue (Tf-1). To analyse metabolic differences associated with the two isoforms, their ratio (Tf-2/Tf-1) was defined as the Tf index. Here we report that Tf indices of patients with tauopathies including Alzheimer's disease (2.29 + 0.64) were similar to those of neurological controls (2.07 + 0.87) (P = 0.147). In contrast, Tf indices with Parkinson's disease (PD, 3.38 ± 1.87) and multiple system atrophy (MSA, 3.15 ± 1.72) were higher than those of the controls (2.07 ± 0.87), the P-values being < 0.001 and 0.024, respectively. Tf indices of PD and MSA did not appear to be normally distributed. Indeed, detrended normal Quantile-Quantile plot analysis revealed the presence of an independent subgroup showing higher Tf indices in PD and MSA. The subgroup of PD showed higher levels of CSF α-synuclein (38.3 ± 17.8 ng/ml) than the rest (25.3 ± 11.3 ng/ml, P = 0.012). These results suggest that PD (and MSA) includes two subgroups, which show different metabolism of CSF transferrin and α-synuclein. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  9. Involvement of Peripheral Nerves in the Transgenic PLP-α-Syn Model of Multiple System Atrophy: Extending the Phenotype.

    PubMed

    Kuzdas-Wood, Daniela; Irschick, Regina; Theurl, Markus; Malsch, Philipp; Mair, Norbert; Mantinger, Christine; Wanschitz, Julia; Klimaschewski, Lars; Poewe, Werner; Stefanova, Nadia; Wenning, Gregor K

    2015-01-01

    Multiple system atrophy (MSA) is a fatal, rapidly progressive neurodegenerative disease with (oligodendro-)glial cytoplasmic α-synuclein (α-syn) inclusions (GCIs). Peripheral neuropathies have been reported in up to 40% of MSA patients, the cause remaining unclear. In a transgenic MSA mouse model featuring GCI-like inclusion pathology based on PLP-promoter driven overexpression of human α-syn in oligodendroglia motor and non-motor deficits are associated with MSA-like neurodegeneration. Since α-syn is also expressed in Schwann cells we aimed to investigate whether peripheral nerves are anatomically and functionally affected in the PLP-α-syn MSA mouse model. To this end, heat/cold as well as mechanical sensitivity tests were performed. Furthermore, in vivo and ex vivo nerve conduction and the G-ratios of the sciatic nerve were analyzed, and thermosensitive ion channel mRNA expression in dorsal root ganglia (DRG) was assessed. The presence of human α-syn in Schwann cells was associated with subtle behavioral impairments. The G-ratio of the sciatic nerve, the conduction velocity of myelinated and unmyelinated primary afferents and the expression of thermosensitive ion channels in the sensory neurons, however, were similar to wildtype mice. Our results suggest that the PNS appears to be affected by Schwann cell α-syn deposits in the PLP-α-syn MSA mouse model. However, there was no consistent evidence for functional PNS perturbations resulting from such α-syn aggregates suggesting a more central cause of the observed behavioral abnormalities. Nonetheless, our results do not exclude a causal role of α-syn in the pathogenesis of MSA associated peripheral neuropathy.

  10. Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy

    PubMed Central

    Bassil, Fares; Fernagut, Pierre-Olivier; Bezard, Erwan; Pruvost, Alain; Leste-Lasserre, Thierry; Hoang, Quyen Q.; Ringe, Dagmar; Petsko, Gregory A.; Meissner, Wassilios G.

    2016-01-01

    Multiple system atrophy (MSA) is a sporadic orphan neurodegenerative disorder. No treatment is currently available to slow down the aggressive neurodegenerative process, and patients die within a few years after disease onset. The cytopathological hallmark of MSA is the accumulation of alpha-synuclein (α-syn) aggregates in affected oligodendrocytes. Several studies point to α-syn oligomerization and aggregation as a mediator of neurotoxicity in synucleinopathies including MSA. C-terminal truncation by the inflammatory protease caspase-1 has recently been implicated in the mechanisms that promote aggregation of α-syn in vitro and in neuronal cell models of α-syn toxicity. We present here an in vivo proof of concept of the ability of the caspase-1 inhibitor prodrug VX-765 to mitigate α-syn pathology and to mediate neuroprotection in proteolipid protein α-syn (PLP-SYN) mice, a transgenic mouse model of MSA. PLP-SYN and age-matched wild-type mice were treated for a period of 11 wk with VX-765 or placebo. VX-765 prevented motor deficits in PLP-SYN mice compared with placebo controls. More importantly, VX-765 was able to limit the progressive toxicity of α-syn aggregation by reducing its load in the striatum of PLP-SYN mice. Not only did VX-765 reduce truncated α-syn, but it also decreased its monomeric and oligomeric forms. Finally, VX-765 showed neuroprotective effects by preserving tyrosine hydroxylase-positive neurons in the substantia nigra of PLP-SYN mice. In conclusion, our results suggest that VX-765, a drug that was well tolerated in a 6 wk-long phase II trial in patients with epilepsy, is a promising candidate to achieve disease modification in synucleinopathies by limiting α-syn accumulation. PMID:27482103

  11. Involvement of Peripheral Nerves in the Transgenic PLP-α-Syn Model of Multiple System Atrophy: Extending the Phenotype

    PubMed Central

    Kuzdas-Wood, Daniela; Irschick, Regina; Theurl, Markus; Malsch, Philipp; Mair, Norbert; Mantinger, Christine; Wanschitz, Julia; Klimaschewski, Lars; Poewe, Werner; Stefanova, Nadia; Wenning, Gregor K.

    2015-01-01

    Multiple system atrophy (MSA) is a fatal, rapidly progressive neurodegenerative disease with (oligodendro-)glial cytoplasmic α-synuclein (α-syn) inclusions (GCIs). Peripheral neuropathies have been reported in up to 40% of MSA patients, the cause remaining unclear. In a transgenic MSA mouse model featuring GCI-like inclusion pathology based on PLP-promoter driven overexpression of human α-syn in oligodendroglia motor and non-motor deficits are associated with MSA-like neurodegeneration. Since α-syn is also expressed in Schwann cells we aimed to investigate whether peripheral nerves are anatomically and functionally affected in the PLP-α-syn MSA mouse model. Results To this end, heat/cold as well as mechanical sensitivity tests were performed. Furthermore, in vivo and ex vivo nerve conduction and the G-ratios of the sciatic nerve were analyzed, and thermosensitive ion channel mRNA expression in dorsal root ganglia (DRG) was assessed. The presence of human α-syn in Schwann cells was associated with subtle behavioral impairments. The G-ratio of the sciatic nerve, the conduction velocity of myelinated and unmyelinated primary afferents and the expression of thermosensitive ion channels in the sensory neurons, however, were similar to wildtype mice. Conclusion Our results suggest that the PNS appears to be affected by Schwann cell α-syn deposits in the PLP-α-syn MSA mouse model. However, there was no consistent evidence for functional PNS perturbations resulting from such α-syn aggregates suggesting a more central cause of the observed behavioral abnormalities. Nonetheless, our results do not exclude a causal role of α-syn in the pathogenesis of MSA associated peripheral neuropathy. PMID:26496712

  12. A Ground-Based Comparison of the Muscle Atrophy Research and Exercise System (MARES) and a Standard Isokinetic Dynamometer

    NASA Technical Reports Server (NTRS)

    Hackney, K. J.; English, K. L.; Redd, E.; DeWitt, J. K.; Ploutz-Snyder, R.; Ploutz-Snyder, L. L.

    2010-01-01

    PURPOSE: 1) To compare the test-to-test reliability of Muscle Atrophy Research and Exercise System (MARES) with a standard laboratory isokinetic dynamometer (ISOK DYN) and; 2) to determine if measures of peak torque and total work differ between devices. METHODS: Ten subjects (6M, 4F) completed two trials on both MARES and an ISOK DYN in a counterbalanced order. Peak torque values at 60 deg & 180 deg / s were obtained from five maximal repetitions of knee extension (KE) and knee flexion (KF). Total work at 180 deg / s was determined from the area under the torque vs. displacement curve during twenty maximal repetitions of KE and KF. Reliability of measures within devices was interpreted from the intraclass correlation coefficient (ICC) and compared between devices using the ratio of the within-device standard deviations. Indicators of agreement for the two devices were evaluated from: 1) a calculation of concordance (rho) and; 2) the correlation between the mean of measures versus the delta difference between measures (m u vs delta). RESULTS: For all outcome measures ICCs were high for both the ISOK DYN (0.95-0.99) and MARES (0.90-0.99). However, ratios of the within-device standard deviation were 1.3 to 4.3 times higher on MARES. On average, a wide range (3.3 to 1054 Nm) of differences existed between the values obtained. Only KE peak torque measured at 60 deg & 180 deg / s showed similarities between devices (rho = 0.91 & 0.87; Pearson's r for m u vs delta = -0.22 & -0.37, respectively). CONCLUSION: Although MARES was designed for use in microgravity it was quite reliable during ground-based testing. However, MARES was consistently more variable than an ISOK DYN. Future longitudinal studies evaluating a change in isokinetic peak torque or total work should be limited within one device.

  13. Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy.

    PubMed

    Bassil, Fares; Fernagut, Pierre-Olivier; Bezard, Erwan; Pruvost, Alain; Leste-Lasserre, Thierry; Hoang, Quyen Q; Ringe, Dagmar; Petsko, Gregory A; Meissner, Wassilios G

    2016-08-23

    Multiple system atrophy (MSA) is a sporadic orphan neurodegenerative disorder. No treatment is currently available to slow down the aggressive neurodegenerative process, and patients die within a few years after disease onset. The cytopathological hallmark of MSA is the accumulation of alpha-synuclein (α-syn) aggregates in affected oligodendrocytes. Several studies point to α-syn oligomerization and aggregation as a mediator of neurotoxicity in synucleinopathies including MSA. C-terminal truncation by the inflammatory protease caspase-1 has recently been implicated in the mechanisms that promote aggregation of α-syn in vitro and in neuronal cell models of α-syn toxicity. We present here an in vivo proof of concept of the ability of the caspase-1 inhibitor prodrug VX-765 to mitigate α-syn pathology and to mediate neuroprotection in proteolipid protein α-syn (PLP-SYN) mice, a transgenic mouse model of MSA. PLP-SYN and age-matched wild-type mice were treated for a period of 11 wk with VX-765 or placebo. VX-765 prevented motor deficits in PLP-SYN mice compared with placebo controls. More importantly, VX-765 was able to limit the progressive toxicity of α-syn aggregation by reducing its load in the striatum of PLP-SYN mice. Not only did VX-765 reduce truncated α-syn, but it also decreased its monomeric and oligomeric forms. Finally, VX-765 showed neuroprotective effects by preserving tyrosine hydroxylase-positive neurons in the substantia nigra of PLP-SYN mice. In conclusion, our results suggest that VX-765, a drug that was well tolerated in a 6 wk-long phase II trial in patients with epilepsy, is a promising candidate to achieve disease modification in synucleinopathies by limiting α-syn accumulation.

  14. Antidepressants reduce neuroinflammatory responses and astroglial alpha-synuclein accumulation in a transgenic mouse model of Multiple System Atrophy

    PubMed Central

    Valera, Elvira; Ubhi, Kiren; Mante, Michael; Rockenstein, Edward; Masliah, Eliezer

    2014-01-01

    Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the pathological accumulation of alpha-synuclein (α-syn) within oligodendroglial cells. This accumulation is accompanied by neuroinflammation with astrogliosis and microgliosis, that leads to neuronal death and subsequent parkinsonism and dysautonomia. Antidepressants have been explored as neuroprotective agents as they normalize neurotrophic factor levels, increase neurogenesis and reduce neurodegeneration, but their anti-inflammatory properties have not been fully characterized. We analyzed the anti-inflammatory profiles of three different antidepressants (fluoxetine, olanzapine and amitriptyline) in the MBP1-hα-syn transgenic (tg) mouse model of MSA. We observed that antidepressant treatment decreased the number of α-syn-positive cells in the basal ganglia of 11-month old tg animals. This reduction was accompanied with a similar decrease in the colocalization of α-syn with astrocyte markers in this brain structure. Consistent with these results, antidepressants reduced astrogliosis in the hippocampus and basal ganglia of the MBP1-hα-syn tg mice, and modulated the expression levels of key cytokines that were dysregulated in the tg mouse model, such as IL-1β. In vitro experiments in the astroglial cell line C6 confirmed that antidepressants inhibited NF-κB translocation to the nucleus and reduced IL-1β protein levels. We conclude that the anti-inflammatory properties of antidepressants in the MBP1-hα-syn tg mouse model of MSA might be related to their ability to inhibit α-syn propagation from oligodendrocytes to astroglia and to regulate transcription factors involved in cytokine expression. Our results suggest that antidepressants might be of interest as anti-inflammatory and α-syn-reducing agents for MSA and other α-synucleinopathies. PMID:24310907

  15. Horse-Expert: An aided expert system for diagnosing horse diseases.

    PubMed

    Qin, H; Xiao, J; Gao, X; Wang, H

    2016-12-01

    In contrast to the rapid development of the horse husbandry in China, the ability of horse veterinarians to diagnose diseases has not been improved and only a few domain experts have considerable expertise. At present, many expert systems have been developed for diseases diagnosis, but few for horse diseases diagnosis have been studied in depth. This paper presents the design and development of a computer-aided expert system for diagnosing horse diseases. We suggest an approach for diagnosis of horse diseases based on the analysis of diagnostic characteristics and the experiential knowledge of domain experts. It is based on using evidence-weighted uncertainty reasoning theory, which is a combination of evidence theory and an uncertainty pass algorithm of confidence factors. It enables drawing of inferences with atypical clinical signs and the uncertainty of the user's subjective understanding. It reduces the influence of subjective factors on diagnostic accuracy. The system utilizes a user friendly interface for users and requests a confidence factor from users when feedback is given to the system. Horse-Expert combines the confidence factors with weight factors assigned to clinical signs by experts during the knowledge acquisition process to make diagnostic conclusions. The system can diagnose 91 common horse diseases, and provides suggestions for appropriate treatment options. In addition, users can check the medical record through statistical charts. The system has been tested in seven demonstration areas of Xinjiang province in northwestern China. By constantly maintaining and updating the knowledge base, the system has potential application in veterinary practice.

  16. Cisplatin triggers atrophy of skeletal C2C12 myotubes via impairment of Akt signalling pathway and subsequent increment activity of proteasome and autophagy systems

    SciTech Connect

    Fanzani, Alessandro Zanola, Alessandra; Rovetta, Francesca; Rossi, Stefania; Aleo, Maria Francesca

    2011-02-01

    Cisplatin (cisPt) is an antineoplastic drug which causes an array of adverse effects on different organs and tissues, including skeletal muscle. In this work we show that cisPt behaves as a potent trigger to activate protein hypercatabolism in skeletal C2C12 myotubes. Within 24 h of 50 {mu}M cisPt administration, C2C12 myotubes displayed unchanged cell viability but showed a subset of hallmark signs typically recognized during atrophy, including severe reduction in body size, repression of Akt phosphorylation, transcriptional up-regulation of atrophy-related genes, such as atrogin-1, gabarap, beclin-1 and bnip-3, and loss of myogenic markers. As a consequence, proteasomal activity and formation of autophagosomes were remarkably increased in cisPt-treated myotubes, but forced stimulation of Akt pathway, as obtained through insulin administration or delivery of a constitutively activated Akt form, was sufficient to counter the cisPt-induced protein breakdown, leading to rescue of atrophic size. Overall, these results indicate that cisPt induces atrophy of C2C12 myotubes via activation of proteasome and autophagy systems, suggesting that the Akt pathway represents one sensitive target of cisPt molecular action in skeletal muscle.

  17. Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy.

    PubMed

    Doppler, Kathrin; Weis, Jessica; Karl, Katharina; Ebert, Sönke; Ebentheuer, Jens; Trenkwalder, Claudia; Klebe, Stephan; Volkmann, Jens; Sommer, Claudia

    2015-10-01

    MSA is characterized by deposition of alpha-synuclein (α-Syn) in oligodendrocytes and central nervous system (CNS) neurons. After recently detecting phospho-α-Syn (p-α-Syn) in dermal nerve fibers of patients with Parkinson's disease (PD), we assessed skin biopsies from patients with MSA to evaluate its potential role as a biomarker. Skin biopsies of patients with MSA (n = 12), idiopathic PD (n = 30), tauopathies (n = 15), and normal controls (n = 39) were analyzed. P-α-Syn within dermal nerves was detected by immunofluorescence staining. p-α-Syn was found in 67% of patients with MSA and Parkinson's disease, but not in patients with tauopathy or controls when analyzing 15 consecutive sections. Sensitivity could be increased to 75% and 73%, respectively, by analyzing serial sections. In contrast to PD, where p-α-Syn clustered in autonomic fibers, deposits were mainly found in unmyelinated somatosensory fibers in MSA. α-Syn pathology in MSA is not restricted to the CNS, and skin biopsy may be useful for the premortem study of p-α-Syn. © 2015 International Parkinson and Movement Disorder Society.

  18. Multiple System Atrophy

    MedlinePlus

    ... progressive loss of nerve cell function (neurodegeneration). Using cell models of MSA, scientists were able to show that damage to mitochondria (cellular “power plants”) and the generation of abnormal alpha-synuclein aggregates ...

  19. [Creating diagnoses and interventions under the auspices of different nursing classification systems].

    PubMed

    da Mata, Luciana Regina Ferreira; de Souza, Cristiane Chaves; Chianca, Tânia Couto Machado; de Carvalho, Emília Campos

    2012-12-01

    This study analyzes the use of different nursing classification systems to meet the standards established by the norm ISO 18.104:2003, based on a fictitious clinical situation. Nursing diagnoses and interventions were created using NANDA-I, NIC and ICNP® and an analysis was performed of the terminology agreement of these classification systems with the model proposed by the norm ISO 18.104:2003. For the creation of nursing diagnoses, NANDA-I and ICNP® comply with norm ISO 18.104:2003. As for the creation of nursing interventions, ICNP® meets the terminology reference model proposed by ISO 18104:2003. NIC, on the other hand, does not propose a combinatory terminology reference model. The unification of nursing terminology depends on reviewing, standardizing and testing these classifications in order to establish a common and sound language for the profession.

  20. Can endoscopic atrophy predict histological atrophy? Historical study in United Kingdom and Japan.

    PubMed

    Kono, Shin; Gotoda, Takuji; Yoshida, Shigeaki; Oda, Ichiro; Kondo, Hitoshi; Gatta, Luigi; Naylor, Greg; Dixon, Michael; Moriyasu, Fuminori; Axon, Anthony

    2015-12-14

    To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan. Using published data, a total of 252 patients, 126 in the United Kingdom and 126 in Japan, aged 20 to 80 years, were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system. The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibility, with a weighted kappa value of 0.76 (P < 0.001). Multivariate analysis showed that three factors were associated with decreased concordance: Japanese ethnicity [odds ratio (OR) 0.22, 95% confidence interval (CI) 0.11-0.43], older age (OR = 0.32, 95%CI: 0.16-0.66) and endoscopic atrophy (OR = 0.10, 95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy, assessed by cancer risk-oriented grading, was reproducible, with a kappa value of 0.81 (95%CI: 0.75-0.87). Only nine patients (3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives. Endoscopic grading can predict histological atrophy with few false negatives, indicating that precancerous conditions can be identified during screening endoscopy, particularly in patients in western countries.

  1. Can endoscopic atrophy predict histological atrophy? Historical study in United Kingdom and Japan

    PubMed Central

    Kono, Shin; Gotoda, Takuji; Yoshida, Shigeaki; Oda, Ichiro; Kondo, Hitoshi; Gatta, Luigi; Naylor, Greg; Dixon, Michael; Moriyasu, Fuminori; Axon, Anthony

    2015-01-01

    AIM: To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan. METHODS: Using published data, a total of 252 patients, 126 in the United Kingdom and 126 in Japan, aged 20 to 80 years, were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system. RESULTS: The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibility, with a weighted kappa value of 0.76 (P < 0.001). Multivariate analysis showed that three factors were associated with decreased concordance: Japanese ethnicity [odds ratio (OR) 0.22, 95% confidence interval (CI) 0.11-0.43], older age (OR = 0.32, 95%CI: 0.16-0.66) and endoscopic atrophy (OR = 0.10, 95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy, assessed by cancer risk-oriented grading, was reproducible, with a kappa value of 0.81 (95%CI: 0.75-0.87). Only nine patients (3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives. CONCLUSION: Endoscopic grading can predict histological atrophy with few false negatives, indicating that precancerous conditions can be identified during screening endoscopy, particularly in patients in western countries. PMID:26673849

  2. A machine independent expert system for diagnosing environmentally induced spacecraft anomalies

    NASA Technical Reports Server (NTRS)

    Rolincik, Mark J.

    1991-01-01

    A new rule-based, machine independent analytical tool for diagnosing spacecraft anomalies, the EnviroNET expert system, was developed. Expert systems provide an effective method for storing knowledge, allow computers to sift through large amounts of data pinpointing significant parts, and most importantly, use heuristics in addition to algorithms which allow approximate reasoning and inference, and the ability to attack problems not rigidly defines. The EviroNET expert system knowledge base currently contains over two hundred rules, and links to databases which include past environmental data, satellite data, and previous known anomalies. The environmental causes considered are bulk charging, single event upsets (SEU), surface charging, and total radiation dose.

  3. Utilization of computer-aided detection system in diagnosing unilateral maxillary sinusitis on panoramic radiographs

    PubMed Central

    Ohashi, Yasufumi; Katsumata, Akitoshi; Fujita, Hiroshi; Nakayama, Miwa; Fukuda, Motoki; Nozawa, Michihito; Ariji, Eiichiro

    2016-01-01

    Objectives: It is unclear whether computer-aided detection (CAD) systems for panoramic radiography can help inexperienced dentists to diagnose maxillary sinusitis. The aim of this study was to clarify whether a CAD system for panoramic radiography can contribute to improved diagnostic performance for maxillary sinusitis by inexperienced dentists. Methods: The panoramic radiographs of 49 patients with maxillary sinusitis and 49 patients with healthy sinuses were evaluated in this study. The diagnostic performance of the CAD system was determined. 12 inexperienced dentists and 4 expert oral and maxillofacial radiologists observed the total of 98 panoramic radiographs and judged the presence or absence of maxillary sinusitis, under conditions with and without the support of the CAD system. The receiver operating characteristic curves of the two groups were compared. Results: The CAD system provided sensitivity of 77.6%, specificity of 69.4% and accuracy of 73.5%. The diagnostic performance of the inexperienced dentists increased with the support of the CAD system. When the inexperienced dentists diagnosed maxillary sinusitis with CAD support, the area under the curve (AUC) was significantly higher than that without CAD support. When the focus was only on panoramic radiographs in which CAD support led to a correct diagnosis, the AUC of the inexperienced dentists increased to an equivalent level to that of the experienced radiologists. Conclusions: The CAD system supported the inexperienced dentists in diagnosing maxillary sinusitis on the panoramic radiographs. If the accuracy of the CAD system can be increased, the benefits of CAD support will be further enhanced. PMID:26837670

  4. Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates.

    PubMed

    Mandel, Ronald J; Marmion, David J; Kirik, Deniz; Chu, Yaping; Heindel, Clifford; McCown, Thomas; Gray, Steven J; Kordower, Jeffrey H

    2017-06-16

    Multiple system atrophy (MSA) is a horrible and unrelenting neurodegenerative disorder with an uncertain etiology and pathophysiology. MSA is a unique proteinopathy in which alpha-synuclein (α-syn) accumulates preferentially in oligodendroglia rather than neurons. Glial cytoplasmic inclusions (GCIs) of α-syn are thought to elicit changes in oligodendrocyte function, such as reduced neurotrophic support and demyelination, leading to neurodegeneration. To date, only a murine model using one of three promoters exist to study this disease. We sought to develop novel rat and nonhuman primate (NHP) models of MSA by overexpressing α-syn in oligodendroglia using a novel oligotrophic adeno-associated virus (AAV) vector, Olig001. To establish tropism, rats received intrastriatal injections of Olig001 expressing GFP. Histological analysis showed widespread expression of GFP throughout the striatum and corpus callosum with >95% of GFP+ cells co-localizing with oligodendroglia and little to no expression in neurons or astrocytes. We next tested the efficacy of this vector in rhesus macaques with intrastriatal injections of Olig001 expressing GFP. As in rats, we observed a large number of GFP+ cells in gray matter and white matter tracts of the striatum and the corpus callosum, with 90-94% of GFP+ cells co-localizing with an oligodendroglial marker. To evaluate the potential of our vector to elicit MSA-like pathology in NHPs, we injected rhesus macaques intrastriatally with Olig001 expressing the α-syn transgene. Histological analysis 3-months after injection demonstrated widespread α-syn expression throughout the striatum as determined by LB509 and phosphorylated serine-129 α-syn immunoreactivity, all of which displayed as tropism similar to that seen with GFP. As in MSA, Olig001-α-syn GCIs in our model were resistant to proteinase K digestion and caused microglial activation. Critically, demyelination was observed in the white matter tracts of the corpus callosum and

  5. Disease severity and progression in progressive supranuclear palsy and multiple system atrophy: validation of the NNIPPS--Parkinson Plus Scale.

    PubMed

    Payan, Christine A M; Viallet, François; Landwehrmeyer, Bernhard G; Bonnet, Anne-Marie; Borg, Michel; Durif, Franck; Lacomblez, Lucette; Bloch, Frédéric; Verny, Marc; Fermanian, Jacques; Agid, Yves; Ludolph, Albert C; Leigh, Peter N; Bensimon, Gilbert

    2011-01-01

    The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362) and Multiple System Atrophy (MSA, n = 398). To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study. Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116), validity (n = 760), and responsiveness (n = 642). Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α ≥ 0.70). Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94) and 9 dimensions (Intra-class coefficient = 0.80-0.93), and moderate (Intra-class coefficient = 0.54-0.77) for 6. Correlations of the total score with other clinical measures of severity were good (rho ≥ 0.70). The total score was significantly and linearly related to survival (p<0.0001). Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10), though higher in PSP (SRM = 1.25) than in MSA (SRM = 1.0), indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall severity and progression was similar. The NNIPPS-PPS has suitable validity, is

  6. Disease Severity and Progression in Progressive Supranuclear Palsy and Multiple System Atrophy: Validation of the NNIPPS – PARKINSON PLUS SCALE

    PubMed Central

    Payan, Christine A. M.; Viallet, François; Landwehrmeyer, Bernhard G.; Bonnet, Anne-Marie; Borg, Michel; Durif, Franck; Lacomblez, Lucette; Bloch, Frédéric; Verny, Marc; Fermanian, Jacques; Agid, Yves; Ludolph, Albert C.

    2011-01-01

    Background The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362) and Multiple System Atrophy (MSA, n = 398). To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study. Methods and Findings Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116), validity (n = 760), and responsiveness (n = 642). Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α≥0.70). Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94) and 9 dimensions (Intra-class coefficient = 0.80–0.93), and moderate (Intra-class coefficient = 0.54–0.77) for 6. Correlations of the total score with other clinical measures of severity were good (rho≥0.70). The total score was significantly and linearly related to survival (p<0.0001). Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10), though higher in PSP (SRM = 1.25) than in MSA (SRM = 1.0), indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall

  7. Parkinsonism in multiple system atrophy: natural history, severity (UPDRS-III), and disability assessment compared with Parkinson's disease.

    PubMed

    Tison, François; Yekhlef, Farid; Chrysostome, Virginie; Balestre, Eric; Quinn, Niall P; Poewe, Werner; Wenning, Gregor K

    2002-07-01

    We analyzed parkinsonian features in multiple system atrophy (MSA) compared with age- and disease duration-matched Parkinson's disease (PD) patients, and assessed the applicability of the Unified Parkinson's Disease Rating Scale (UPDRS) -III motor scale as a means of rating their severity. Cross-sectional analysis of parkinsonism was done using UPDRS-III, International Cerebellar Atatia Rating Scale, and disability scales (Hoehn and Yahr [H&A], Schwab and England, Katz and Lawton) in 50 unselected MSA patients and in 50 matched PD patients. At symptom onset, falls occurred 10 times more frequently in MSA, whereas limb tremor was 10 times more common in PD. At first visit (10.2 months), hemiparkinsonism and pill-rolling rest tremor were less common in MSA. Hypomimia, atypical rest, postural or action tremor, as well as postural instability were more frequent in MSA. At study examination (62.4 months), parkinsonian signs in MSA patients were more frequently symmetrical and associated with axial rigidity, antecollis and postural instability. A levodopa response of >50% was seen in <10% of MSA patients. Modified H&Y stages (3.2 +/- 1.3 vs. 2.2 +/- 0.78) and UPDRS-III scores (48.14 +/- 19.5 vs. 31.74 +/- 12.9) were significantly (P = 0.0001) higher in MSA. The internal consistency of the UPDRS-III was fair in MSA patients (Cronbach's alpha >0.90), and correlated well with marked dependency on the Schwab and England and Katz and Lawton scales. Factor structure analysis of UPDRS-III in MSA showed five clinically distinct subscores accounting for 74% of the variance, differing from PD by the dependency of the face-speech and limb bradykinesia items and independence of the postural-action tremor from the rest tremor items. There was a significant correlation (R(2) = 0.70, P = 0.001) between ICARS ataxia and UPDRS-III scores in MSA patients. Results confirm a distinct profile of parkinsonism in MSA and greater severity and disability compared with PD. It also indicates that

  8. Correlation of Brain Atrophy, Disability, and Spinal Cord Atrophy in a Murine Model of Multiple Sclerosis.

    PubMed

    Paz Soldán, M Mateo; Raman, Mekala R; Gamez, Jeffrey D; Lohrey, Anne K; Chen, Yi; Pirko, Istvan; Johnson, Aaron J

    2015-01-01

    Disability progression in multiple sclerosis (MS) remains incompletely understood. Unlike lesional measures, central nervous system atrophy has a strong correlation with disability. Theiler's murine encephalomyelitis virus infection in SJL/J mice is an established model of progressive MS. We utilized in vivo MRI to quantify brain and spinal cord atrophy in this model and analyzed the temporal relationship between atrophy and disability. Infected and control mice were followed for 12 months. Disability was assessed periodically using rotarod assay. Volumetric MRI datasets were acquired at 7 Tesla. Ventricular volume and C4-5 spinal cord cross-sectional area measurements were performed using Analyze 10. At 3 months, brain atrophy reached statistical significance (P = .005). In contrast, disability did not differ until 4 months post-infection (P = .0005). Cord atrophy reached significance by 9 months (P = 0.009). By 12 months, brain atrophy resulted in 111.8% increased ventricular volume (P = .00003), while spinal cord cross-sectional area was 25.6% reduced (P = .001) among cases. Our results suggest that significant brain atrophy precedes and predicts the development of disability, while spinal cord atrophy occurs late and correlates with severe disability. The observed temporal relationship establishes a framework for mechanisms of disability progression and enables further investigations of their underlying substrate. Copyright © 2015 by the American Society of Neuroimaging.

  9. [A clinical report of five cases of central nervous system miliary tuberculomas first diagnosed by neurologists].

    PubMed

    Huang, X; Wang, X Y; Zhu, Z H; Qi, X K; Yu, Y X

    2017-03-01

    To explore the clinical characteristics and imaging features of miliary tuberculomas in central nervous system(CNS). A total of 5 cases diagnosed with tuberculosis in CNS first diagnosed by neurologists in Navy General Hospital of PLA were enrolled in the study. All clinical and imaging data were collected and analyzed retrospectively. The main initial symptoms were fever and headache (4/5). Multiple diffused miliary lesions were shown by brain MRI, with maximum diameter ranged from 1-4 mm and ring-shape or nodular enhancement after gadolinium injection. As mycobacterium tuberculosis could seldomly be found in serum and cerebrospinal fluid, contrast MRI remains the effective method for detecting miliary tuberculomas in CNS.

  10. Molecular evidence for central nervous system involvement in children with newly diagnosed acute lymphoblastic leukemia.

    PubMed

    Januszkiewicz, D A; Nowak, J S

    1995-01-01

    Central nervous system (CNS) involvement in children with newly diagnosed acute lymphoblastic leukemia (ALL) would have profound implication for the prognosis and accurate stratification of CNS prophylactic therapy. Using PCR technique with specific primers for V, D and J segments of TCRD gene, the pattern of TCRD gene rearrangements in bone marrow lymphoblasts and in cells from cerebrospinal fluid (CSF) have been investigated. The study involved 21 children at the time of diagnosis with B-lineage ALL. In nine of 21 patients incomplete TCRDVD gene rearrangement has been found in CSF cells, which was identical to that observed in bone marrow of the same children. It can be concluded that at least in 43 per cent of all analysed cases, there were signs of CNS involvement in newly diagnosed ALL patients.

  11. [Etiological diagnosis of villous atrophy].

    PubMed

    Patey-Mariaud De Serre, N; Verkarre, V; Cellier, C; Cerf-Bensussan, N; Schmitz, J; Brousse, N

    2001-08-01

    Villous atrophy may have various etiologies. The diagnosis of villous atrophy relies on an intestinal biopsy which necessitates a perfect histological technique to assert the villous atrophy and its degree. The most frequent etiology is coeliac disease. Villous atrophy regresses with gluten free diet. The failure of a strict gluten free diet implies to exclude a refractory sprue thought to be the earliest form of enteropathy associated T cell lymphoma. The other etiologies of villous atrophy are unusual and could be observed in alpha chain disease, inflammatory and infectious diseases, immune disorders, and primitive ileal villous atrophy. Other etiologies characterize villous atrophy in children as cow milk allergy and epithelial abnormalities.

  12. Progressive hemifacial atrophy

    PubMed Central

    Sande, Abhijeet; Risbud, Mukund; Kshar, Avinash; Paranjpe, Arati Oka

    2013-01-01

    Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an uncommon degenerative and poorly understood condition. It is characterized by a slow and progressive but self-limited atrophy affecting one side of the face. The incidence and the cause of this alteration are unknown. A cerebral disturbance of fat metabolism has been proposed as a primary cause. Possible factors that are involved in the pathogenesis include trauma, viral infections, heredity, endocrine disturbances and auto-immunity. The most common complications that appear in association to this disorder are: trigeminal neuralgia, facial paresthesia, severe headache and epilepsy. Characteristically, the atrophy progresses slowly for several years and, it becomes stable. The objective of this work is, through the presentation of a clinical case, to accomplish a literature review concerning general characteristics, etiology, physiopathology and treatment of progressive hemifacial atrophy. PMID:23878573

  13. Hypoactivation of reward motivational system in patients with newly diagnosed hypertension grade I-II.

    PubMed

    Aftanas, L I; Brak, I V; Gilinskaya, O M; Korenek, V V; Pavlov, S V; Reva, N V

    2014-08-01

    In patients with newly diagnosed untreated grade I-II hypertension, EEG oscillations were recorded under conditions activation of the two basic motivational systems, defensive motivational system and positive reinforcement system, evoked by recall of personally meaningful emotional events. The 64-channel EEG and cardiovascular reactivity (beat-by-beat technology) were simultaneously recorded. At rest, hypertensive patients had significantly reduced platelet serotonin concentrations in comparison with healthy individuals. The patients experiencing emotional activation were characterized by significantly lower intensity of positive emotions associated with more pronounced suppression of EEG activity in the delta (2-4 Hz) and theta (ranges of frequency 4-6 and 6-8 Hz) oscillators in the parieto-occipital cortex (zones P and PO) in both hemispheres of the brain. The findings attest to insufficient function of the brain serotonin system and hypoactivation of the reward/reinforcement system in patients with primary hypertension.

  14. Wolfram Syndrome presenting with optic atrophy and diabetes mellitus: two case reports.

    PubMed

    Manaviat, Masoud Reza; Rashidi, Maryam; Mohammadi, Seyed Mohammad

    2009-12-19

    Wolfram syndrome is the constellation of juvenile onset diabetes mellitus and optic atrophy, known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness).Patients demonstrate diabetes mellitus followed by optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts early in the third decade, and multiple neurological abnormalities early in the fourth decade.This study reports two siblings with late diagnosed wolfram syndrome with diabetes insipidus, diabetes mellitus, optic atrophy, deafness and severe urological abnormalities.In conclusion, cases having early onset insulin-dependent diabetes mellitus and optic atrophy together need to be evaluated with respect to Wolfram.

  15. Wolfram Syndrome presenting with optic atrophy and diabetes mellitus: two case reports

    PubMed Central

    2009-01-01

    Wolfram syndrome is the constellation of juvenile onset diabetes mellitus and optic atrophy, known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). Patients demonstrate diabetes mellitus followed by optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts early in the third decade, and multiple neurological abnormalities early in the fourth decade. This study reports two siblings with late diagnosed wolfram syndrome with diabetes insipidus, diabetes mellitus, optic atrophy, deafness and severe urological abnormalities. In conclusion, cases having early onset insulin-dependent diabetes mellitus and optic atrophy together need to be evaluated with respect to Wolfram. PMID:20062605

  16. [Correlations between serum 25-hydroxyvitamin D and cytokines in patients newly diagnosed with systemic lupus erythematosus].

    PubMed

    Su, Jiang; Zhu, Jing; Dong, Wei; Long, Li; Long, Wubin; Chen, Xixi

    2016-12-01

    Objective To investigate the correlations between serum 25-hydroxyvitamin D (25-OH-VitD) and serum cytokines of interferon (IFN)-α2, interleukin(IL)-6, IL-10, and IL-17A in Chinese Han patients newly diagnosed with systemic lupus erythematosus (SLE). Methods This study recruited 86 Chinese patients newly diagnosed with SLE and 73 healthy volunteers. The serum 25-OH-VitD was detected using ELISA. The serum levels of IFN-α2, IL-6, IL-10 and IL-17A were detected using Luminex liquichip. The associations between serum 25-OH-VitD and serum cytokines, clinical manifestations and laboratory findings were analyzed using Spearman linear correlation analysis. Results The serum 25-OH-VitD was significantly lower in SLE patients than in healthy controls. The serum 25-OH-VitD was positively correlated with serum C3, negatively correlated with serum IL-17A and 24 hour urine protein excretion, but not obviously correlated with serum IFN-α2, IL-6 and IL-10. Conclusion The serum 25-OH-VitD decreases in Chinese patients newly diagnosed with SLE and it is negatively correlated with serum IL-17A.

  17. Wireless telemedicine systems for diagnosing sleep disorders with Zigbee star network topology

    NASA Astrophysics Data System (ADS)

    Oh, Sechang; Kwon, Hyeokjun; Varadan, Vijay K.

    2012-10-01

    Good sleep is critical for one's overall physical and mental health but more than 50 million Americans have experienced or are suffering from sleep disorders. Nevertheless, 85% of them remain undiagnosed or untreated. They can lead to chronic diseases. Sleep disorders are diagnosed through polysomnography, also known as sleep study, performed in a sleep laboratory overnight. This perturbs his/her daily sleep routine, and consequently, an accurate diagnosis cannot be made. Many companies have been developing home sleep test systems to reduce the cost of sleep studies and provide a more convenience solution to patients. The category of the system varies as type II, type III and type IV according to the type of sleep study. Current systems cannot be easily extended from one type to include a higher type. A patient who has a type III system to diagnose sleep apnea should additionally purchase a type II system which has functions that overlap with a type III system, to evaluate sleep stages. In this paper, we propose a wireless telemedicine system for easy extension of channels using the start network topology of the Zigbee protocol. The HST system consists of two wireless HST devices with a Zigbee module, a wireless HST receiver with both a Zigbee and a Wi-Fi module, and a sever which monitors/saves the physiological signals. One transmitter provides 5 channels for 2x EOG, 2x EEG and EMG to evaluate sleep stages. The other transmitter provides 5 additional channels for ECG, nasal air flow, body position, abdominal/chest efforts and oxygen saturation to diagnose sleep apnea. These two transmitters, acting as routers, and the receiver as a coordinator form a Zigbee star network. The data from each transmitter in the receiver are retransmitted to the monitoring unit through Wi-Fi. By building a star network with Zigbee, channels can be easily extended so that low level systems can be upgraded to higher level systems by simply adding the necessary channels. In addition

  18. Dorfin Localizes to the Ubiquitylated Inclusions in Parkinson’s Disease, Dementia with Lewy Bodies, Multiple System Atrophy, and Amyotrophic Lateral Sclerosis

    PubMed Central

    Hishikawa, Nozomi; Niwa, Jun-ichi; Doyu, Manabu; Ito, Takashi; Ishigaki, Shinsuke; Hashizume, Yoshio; Sobue, Gen

    2003-01-01

    In many neurodegenerative diseases, the cytopathological hallmark is the presence of ubiquitylated inclusions consisting of insoluble protein aggregates. Lewy bodies in Parkinson’s disease and dementia with Lewy bodies disease, glial cell inclusions in multiple system atrophy, and hyaline inclusions in amyotrophic lateral sclerosis (ALS) are representative of these inclusions. The elucidation of the components of these inclusions and the mechanisms underlying inclusion formation is important in uncovering the pathogenesis of these disorders. We hypothesized that Dorfin, a perinuclearly located E3 ubiquitin ligase, participates in the formation of ubiquitylated inclusions in a wide range of neurodegenerative diseases. Here, we report that affinity-purified anti-Dorfin antibody labeled ubiquitylated inclusions of Parkinson’s disease, dementia with Lewy bodies disease, multiple system atrophy, and sporadic and familial ALS. A double-immunofluorescence study revealed that Dorfin shows a distribution pattern parallel to that of ubiquitin. Furthermore, by a filter trap assay, we detected that Dorfin is present in the ubiquitylated high-molecular weight structures derived from these diseases. These results suggest that Dorfin plays a crucial role in the formation of ubiquitylated inclusions of α-synucleinopathy and ALS. However, because we failed to show the direct binding of α-synuclein with Dorfin, future investigations into the binding partner(s) of Dorfin will be needed to deepen our understanding of the pathophysiology of α-synucleinopathy and ALS. PMID:12875980

  19. [MSA-QoL: disease-specific questionnaire to assess health-related quality of life in multiple system atrophy: validation of the German translation].

    PubMed

    Krismer, F; Duerr, S; Minnerop, M; Klockgether, T; Stamelou, M; Eggert, K M; Oertel, W H; Schrag, A; Poewe, W; Wenning, G K

    2013-06-01

    Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder which causes early sustained disability and quality of life impairment. Recently, a self-reported questionnaire focusing on MSA-specific symptoms (Multiple System Atrophy Quality of Life questionnaire, MSA-QoL) was developed in the English language. This article reports the validation of the German translation of the MSA-QoL. Translation of the MSA-QoL was implemented in a 3-tiered approach including a forward translation, a back translation and an independent review. For the validation study 38 consecutive patients with MSA according to the consensus criteria were recruited by the participating centers in a German-Austrian cohort. Data were analyzed using standard psychometric procedures. As determined by the independent review, the German translation of the MSA-QoL was classified as fully equivalent to the English version. The validation study confirmed good psychometric properties of the rating scale. The German translation of the MSA-QoL was shown to be a reliable patient-reported rating scale to determine health-related quality of life in MSA patients.

  20. Bed Rest Muscular Atrophy

    NASA Technical Reports Server (NTRS)

    Greenleaf, John E.

    2000-01-01

    A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

  1. Bed Rest Muscular Atrophy

    NASA Technical Reports Server (NTRS)

    Greenleaf, John E.

    2000-01-01

    A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

  2. In vivo evaluation of gray and white matter volume loss in the parkinsonian variant of multiple system atrophy using SPM8 plus DARTEL for VBM.

    PubMed

    Shigemoto, Yoko; Matsuda, Hiroshi; Kamiya, Kouhei; Maikusa, Norihide; Nakata, Yasuhiro; Ito, Kimiteru; Ota, Miho; Matsunaga, Naofumi; Sato, Noriko

    2013-01-01

    In multiple system atrophy with predominant parkinsonism (MSA-P), several voxel-based morphometry (VBM) studies have revealed gray matter loss; however, the white matter volume changes have been rarely reported. We investigated the volume changes of white matter as well as gray matter by VBM. A retrospective MRI study was performed in 20 patients with MSA-P and 30 age-matched healthy controls. We applied VBM with statistical parametric mapping (SPM8) plus diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) to explore the regional atrophy of gray and white matter in all of the MSA-P patients, 14 patients with left-side dominant and 6 patients with right-side dominant onset as compared to controls. In all of the MSA-P patients, VBM revealed a significant volume reduction of gray matter in the bilateral putamina, cerebellums and dorsal midbrain. White matter loss was located in bilateral globus pallidi, external capsules extending to the midbrain, right subcortical to precentral area through internal capsule, the pons, bilateral middle cerebellar peduncles and left cerebellum. In left-side dominant MSA-P patients, the gray and white matter volume loss was detected predominantly on the right side and vice versa in right-side dominant MSA-P patients. A correlation with disease duration and severity was not detected. VBM using SPM8 plus DARTEL detected significant volume loss not only in the gray but also in the white matter of the area affected by MSA-P.

  3. Siblings’ Perceptions of Their ADHD-Diagnosed Sibling’s Impact on the Family System

    PubMed Central

    King, Kerry; Alexander, Daleen; Seabi, Joseph

    2016-01-01

    This qualitative study explored siblings’ perceptions of the impact a sibling diagnosed with ADHD has within the family system. Specific focus was placed on the different ways these different sibling cohorts were parented. Participants constituted eight adult females with a mean age of 20 years from different cultural and socio-economic backgrounds in the province of Gauteng, South Africa. Data was collected using semi-structured interviews and was analysed thematically. The four themes that emerged from the interviews include differential parental treatment, rejection, discrepancy with discipline, and the parentified child. Specifically, the results of this study revealed feelings of differential parental treatment and discipline that took place in the home and rejection experienced by the non-ADHD sibling. There was also a common theme of a parentified child, who had to carry a burden of caring for their sibling with ADHD. The non-diagnosed siblings perceive themselves to be particularly negatively impacted. The results are discussed in light of the previous empirical studies, and recommendations are made. PMID:27649212

  4. Improvements of Vaginal Atrophy without Systemic Side Effects after Topical Application of Pueraria mirifica, a Phytoestrogen-rich Herb, in Postmenopausal Cynomolgus Macaques

    PubMed Central

    JAROENPORN, Sukanya; URASOPON, Nontakorn; WATANABE, Gen; MALAIVIJITNOND, Suchinda

    2014-01-01

    The estrogenic efficacy of topical vaginal application of Pueraria mirifica extract (PM) on the restoration of vaginal atrophy, and the presence of any systemic side effects, were investigated in postmenopausal cynomolgus macaques. Twelve postmenopausal cynomolgus macaques, with complete cessation of menstruation for at least 5 years before start of this experiment, were divided into three groups. They received a topical vaginal application daily of 0.1 or 1% (w/w) PM cream or a conjugated equine estrogen (CEE) cream (a mixture of estrone, equilin, 17β-dihydroequilin, 17α-estradiol and 17α-dihydroequilin at 0.625 mg total estrogen/g cream) for 28 days. Estrogenic efficacy was assessed weekly by vaginal cytology assay and vaginal pH measurement, whilst the plasma luteinizing hormone (LH) and sex skin coloration levels were determined at the end of each treatment period to evaluate the systemic side effects. PM significantly increased the proportion of superficial cells in a dose-dependent manner, with a similar efficacy between 1% (w/w) PM and CEE. Together with increased vaginal maturation, PM decreased the vaginal pH to acidic levels, as observed in the CEE group. PM induced no detected systemic side effects, whilst CEE decreased the plasma LH level and increased the reddish color of the sex skin during the posttreatment period. Topical vaginal treatment with PM stimulated the maturation of the vaginal epithelium without causing systemic side effects in postmenopausal monkeys. The implication is that PM could be a safer alternative to treat vaginal atrophy in postmenopausal women. PMID:24748397

  5. Improvements of vaginal atrophy without systemic side effects after topical application of Pueraria mirifica, a phytoestrogen-rich herb, in postmenopausal cynomolgus macaques.

    PubMed

    Jaroenporn, Sukanya; Urasopon, Nontakorn; Watanabe, Gen; Malaivijitnond, Suchinda

    2014-01-01

    The estrogenic efficacy of topical vaginal application of Pueraria mirifica extract (PM) on the restoration of vaginal atrophy, and the presence of any systemic side effects, were investigated in postmenopausal cynomolgus macaques. Twelve postmenopausal cynomolgus macaques, with complete cessation of menstruation for at least 5 years before start of this experiment, were divided into three groups. They received a topical vaginal application daily of 0.1 or 1% (w/w) PM cream or a conjugated equine estrogen (CEE) cream (a mixture of estrone, equilin, 17β-dihydroequilin, 17α-estradiol and 17α-dihydroequilin at 0.625 mg total estrogen/g cream) for 28 days. Estrogenic efficacy was assessed weekly by vaginal cytology assay and vaginal pH measurement, whilst the plasma luteinizing hormone (LH) and sex skin coloration levels were determined at the end of each treatment period to evaluate the systemic side effects. PM significantly increased the proportion of superficial cells in a dose-dependent manner, with a similar efficacy between 1% (w/w) PM and CEE. Together with increased vaginal maturation, PM decreased the vaginal pH to acidic levels, as observed in the CEE group. PM induced no detected systemic side effects, whilst CEE decreased the plasma LH level and increased the reddish color of the sex skin during the posttreatment period. Topical vaginal treatment with PM stimulated the maturation of the vaginal epithelium without causing systemic side effects in postmenopausal monkeys. The implication is that PM could be a safer alternative to treat vaginal atrophy in postmenopausal women.

  6. Quasi-optical design for systems to diagnose the electron temperature and density fluctuations on EAST

    SciTech Connect

    Cao, Qifo; Liu, Yong; Zhao, Hailin Zhou, Tianfu; Ti, Ang; Hu, Liqun

    2016-11-15

    A system to simultaneously diagnose the electron temperature and density fluctuations is proposed for Experimental Advanced Superconducting Tokamak device. This system includes a common quasi-optical antenna, a correlation electron cyclotron emission (CECE) system that is used to measure the electron temperature fluctuations and a Doppler backscattering (DBS) system that is used to measure the electron density fluctuations. The frequency range of the proposed CECE system is 108-120 GHz, and this corresponds to a radial coverage of normalized radius ((R − R{sub 0})/a, R{sub 0} = 1850 mm, a = 450 mm) from 0.2 to 0.67 for the plasma operation with a toroidal magnetic field of 2.26 T. This paper focuses on the design of the quasi-optical antenna and aims at optimizing the poloidal resolution for different frequency bands. An optimum result gives the beam radius for the CECE system of 13-15 mm and this corresponds to a wave number range of k{sub θ} < 2.4 cm{sup −1}. The beam radius is 20-30 mm for V band (50-75 GHz) and 15-20 mm for W band (75-110 GHz).

  7. Quasi-optical design for systems to diagnose the electron temperature and density fluctuations on EAST.

    PubMed

    Cao, Qifo; Liu, Yong; Zhao, Hailin; Zhou, Tianfu; Ti, Ang; Hu, Liqun

    2016-11-01

    A system to simultaneously diagnose the electron temperature and density fluctuations is proposed for Experimental Advanced Superconducting Tokamak device. This system includes a common quasi-optical antenna, a correlation electron cyclotron emission (CECE) system that is used to measure the electron temperature fluctuations and a Doppler backscattering (DBS) system that is used to measure the electron density fluctuations. The frequency range of the proposed CECE system is 108-120 GHz, and this corresponds to a radial coverage of normalized radius ((R - R0)/a, R0 = 1850 mm, a = 450 mm) from 0.2 to 0.67 for the plasma operation with a toroidal magnetic field of 2.26 T. This paper focuses on the design of the quasi-optical antenna and aims at optimizing the poloidal resolution for different frequency bands. An optimum result gives the beam radius for the CECE system of 13-15 mm and this corresponds to a wave number range of kθ < 2.4 cm(-1). The beam radius is 20-30 mm for V band (50-75 GHz) and 15-20 mm for W band (75-110 GHz).

  8. Quasi-optical design for systems to diagnose the electron temperature and density fluctuations on EAST

    NASA Astrophysics Data System (ADS)

    Cao, Qifo; Liu, Yong; Zhao, Hailin; Zhou, Tianfu; Ti, Ang; Hu, Liqun

    2016-11-01

    A system to simultaneously diagnose the electron temperature and density fluctuations is proposed for Experimental Advanced Superconducting Tokamak device. This system includes a common quasi-optical antenna, a correlation electron cyclotron emission (CECE) system that is used to measure the electron temperature fluctuations and a Doppler backscattering (DBS) system that is used to measure the electron density fluctuations. The frequency range of the proposed CECE system is 108-120 GHz, and this corresponds to a radial coverage of normalized radius ((R - R0)/a, R0 = 1850 mm, a = 450 mm) from 0.2 to 0.67 for the plasma operation with a toroidal magnetic field of 2.26 T. This paper focuses on the design of the quasi-optical antenna and aims at optimizing the poloidal resolution for different frequency bands. An optimum result gives the beam radius for the CECE system of 13-15 mm and this corresponds to a wave number range of kθ < 2.4 cm-1. The beam radius is 20-30 mm for V band (50-75 GHz) and 15-20 mm for W band (75-110 GHz).

  9. An on-line expert system for diagnosing environmentally induced spacecraft anomalies using CLIPS

    NASA Technical Reports Server (NTRS)

    Lauriente, Michael; Rolincik, Mark; Koons, Harry C; Gorney, David

    1993-01-01

    A new rule-based, expert system for diagnosing spacecraft anomalies is under development. The knowledge base consists of over two-hundred rules and provide links to historical and environmental databases. Environmental causes considered are bulk charging, single event upsets (SEU), surface charging, and total radiation dose. The system's driver translates forward chaining rules into a backward chaining sequence, prompting the user for information pertinent to the causes considered. The use of heuristics frees the user from searching through large amounts of irrelevant information (varying degrees of confidence in an answer) or 'unknown' to any question. The expert system not only provides scientists with needed risk analysis and confidence estimates not available in standard numerical models or databases, but it is also an effective learning tool. In addition, the architecture of the expert system allows easy additions to the knowledge base and the database. For example, new frames concerning orbital debris and ionospheric scintillation are being considered. The system currently runs on a MicroVAX and uses the C Language Integrated Production System (CLIPS).

  10. Diagnosing Disaster Resilience of Communities as Multi-scale Complex Socio-ecological Systems

    NASA Astrophysics Data System (ADS)

    Liu, Wei; Mochizuki, Junko; Keating, Adriana; Mechler, Reinhard; Williges, Keith; Hochrainer, Stefan

    2014-05-01

    Global environmental change, growing anthropogenic influence, and increasing globalisation of society have made it clear that disaster vulnerability and resilience of communities cannot be understood without knowledge on the broader social-ecological system in which they are embedded. We propose a framework for diagnosing community resilience to disasters, as a form of disturbance to social-ecological systems, with feedbacks from the local to the global scale. Inspired by iterative multi-scale analysis employed by Resilience Alliance, the related socio-ecological systems framework of Ostrom, and the sustainable livelihood framework, we developed a multi-tier framework for thinking of communities as multi-scale social-ecological systems and analyzing communities' disaster resilience and also general resilience. We highlight the cross-scale influences and feedbacks on communities that exist from lower (e.g., household) to higher (e.g., regional, national) scales. The conceptual framework is then applied to a real-world resilience assessment situation, to illustrate how key components of socio-ecological systems, including natural hazards, natural and man-made environment, and community capacities can be delineated and analyzed.

  11. An Intelligent computer-aided tutoring system for diagnosing anomalies of spacecraft in operation

    NASA Technical Reports Server (NTRS)

    Rolincik, Mark; Lauriente, Michael; Koons, Harry C.; Gorney, David

    1993-01-01

    A new rule-based, expert system for diagnosing spacecraft anomalies is under development. The knowledge base consists of over two-hundred (200) rules and provides links to historical and environmental databases. Environmental causes considered are bulk charging, single event upsets (SEU), surface charging, and total radiation dose. The system's driver translates forward chaining rules into a backward chaining sequence, prompting the user for information pertinent to the causes considered. When the user selects the novice mode, the system automatically gives detailed explanations and descriptions of terms and reasoning as the session progresses, in a sense teaching the user. As such it is an effective tutoring tool. The use of heuristics frees the user from searching through large amounts of irrelevant information and allows the user to input partial information (varying degrees of confidence in an answer) or 'unknown' to any question. The system is available on-line and uses C Language Integrated Production System (CLIPS), an expert shell developed by the NASA Johnson Space Center AI Laboratory in Houston.

  12. Research opportunities in muscle atrophy

    NASA Technical Reports Server (NTRS)

    Herbison, G. J. (Editor); Talbot, J. M. (Editor)

    1984-01-01

    Muscle atrophy in a weightless environment is studied. Topics of investigation include physiological factors of muscle atrophy in space flight, biochemistry, countermeasures, modelling of atrophied muscle tissue, and various methods of measurement of muscle strength and endurance. A review of the current literature and suggestions for future research are included.

  13. Spinal Muscular Atrophy

    MedlinePlus

    ... are most often affected. Complications include scoliosis and chronic shortening of muscles or tendons around joints. × Definition Spinal Muscular Atrophy (SMA) Types I, II, and III belong to a group of hereditary diseases that cause weakness and wasting of the voluntary muscles in the arms and ...

  14. Frequent globular neuronal cytoplasmic inclusions in the medial temporal region as a possible characteristic feature in multiple system atrophy with dementia.

    PubMed

    Homma, Taku; Mochizuki, Yoko; Komori, Takashi; Isozaki, Eiji

    2016-10-01

    Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease, which is characterized clinically by parkinsonism, cerebellar ataxia and/or autonomic dysfunction, and pathologically by alpha-synuclein-related multisystem neurodegeneration, so-called alpha-synucleinopathy, which particularly involves the striatonigral and olivopontocerebellar systems, with glial cytoplasmic inclusions and neuronal cytoplasmic/nuclear inclusions (NCIs/NNIs). In the recent consensus criteria for the diagnosis of MSA, dementia is described as one of the features not supporting a diagnosis of MSA. However, MSA with dementia has been reported, although the location of the lesion responsible for the dementia remains unclear. In the present study, we aimed to investigate where this lesion may be found, by analyzing 12 autopsy-proven MSA cases, with a particular focus on the medial temporal region. Three of 12 cases with MSA had dementia (MSA-D). Compared with MSA cases without dementia, MSA-D cases had frequent globular NCIs (G-NCIs) in the medial temporal region, especially in their subiculum. In addition, MSA-D cases could be divided into two types; MSA-D with distinct fronto-temporal lobar degeneration (FTLD type) and without distinct fronto-temporal lobar degeneration (non-FTLD type). There was no association between dementia and Alzheimer pathologies, such as neurofibrillary tangles and senile plaques. We suggest that frequent G-NCIs in the medial temporal region, and particularly the subiculum, is one of the important pathological findings of MSA-D, even when a case with MSA-D reveals no significant cerebral atrophy.

  15. Clinical trials in spinal muscular atrophy.

    PubMed

    Kaufmann, Petra; Iannaccone, Susan T

    2008-08-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by muscle atrophy and weakness due to degeneration of the anterior horn cells in the spinal cord. A great need exists for an effective treatment of SMA, a disease that often causes severe disability in patients who are cognitively intact and can have a normal life expectancy. Unlike many other neurologic diseases, SMA can be easily diagnosed through genetic testing. Also, preclinical progress over the last 2 decades has been major, with the discovery of the gene and of a "druggable" modifying gene that provides one of several promising targets for treatment. SMA is rare but is a common orphan disease, so trials should be feasible, raising the hope that we will find effective treatments for this disorder.

  16. Comparative assessment of rule-based and Bayes' theorem as inference engines in diagnosing symptoms for Islamic medication expert system

    NASA Astrophysics Data System (ADS)

    Daud, H.; Razali, R.; Low, T. J.; Sabdin, M.; Zafrul, S. Z. Mohd

    2014-06-01

    An expert system for diagnosing sickness and suggesting treatment based on Islamic Medication (IM) was constructed using Rule Based (RB) and Bayes' theorem (BT) algorithms independently as its inference engine. Comparative assessment on the quality of diagnosing based on symptoms provided by users for certain type of sickness using RB and BT reasoning that lead to the suggested treatment (based on IM) are discussed. Both approaches are found to be useful, each has its own advantages and disadvantages. Major difference of the two algorithms is the selection of symptoms during the diagnosing process. For BT, likely combinations of symptoms need to be classified for each sickness before the diagnosing process. This eliminates any irrelevant sickness based on the combination of symptoms provided by user and combination of symptoms that is unlikely. This is not the case for RB, it will diagnose the sickness as long as one the symptoms is related to the sickness regardless of unlikely combination. Few tests have been carried out using combinations of symptoms for same sickness to investigate their diagnosing accuracy in percentage. BT gives more promising diagnosing results compared to RB for each sickness that comes with common symptoms.

  17. Getting Diagnosed

    MedlinePlus

    ... also for those with related disorders. How is Marfan syndrome diagnosed? getting_diagnosed.jpg A Marfan diagnosis ... spinal column). Is there a genetic test for Marfan syndrome? Genetic testing can provide helpful information in ...

  18. Unyvero i60 implant and tissue infection (ITI) multiplex PCR system in diagnosing periprosthetic joint infection.

    PubMed

    Hischebeth, Gunnar T R; Randau, Thomas M; Buhr, Johanna K; Wimmer, Matthias D; Hoerauf, Achim; Molitor, Ernst; Bekeredjian-Ding, Isabelle; Gravius, Sascha

    2016-02-01

    Periprosthetic joint infection (PJI) is one of the most challenging complications in orthopedic surgery. In cases of suspected periprosthetic joint infection several diagnostic methods are available. In this study we investigated the performance of the newly available Unyvero i60 implant and tissue infection (ITI) multiplex PCR System. 62 specimens from 31 patients with suspected PJI or aseptic loosening of a painful joint arthoplasty were included in this study. Besides the established diagnostic procedures we included a commercial multiplex PCR detection system for diagnosis of PJI. The PCR results obtained from analysis of sonication and synovial fluids (62 specimens) showed a sensitivity of 66.7%, a specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 68.4% when compared to cultural methods. Notably, cultures from sonication fluid displayed a sensitivity of 88.9%, a specificity of 61.5%, a PPV of 76.2% and a NPV of 80.0% when compared to tissue cultures. In conclusion, multiplex PCR is an additional - rapid - method for diagnosing PJI. Positive results with the PCR assay used in this study were always confirmed by subsequent matching culture positivity. However, apart from the time saved the nucleic acid amplification technique did not yield additional information than that obtained from microbiological cultures.

  19. Gender differences in disease activity and clinical features in newly diagnosed systemic lupus erythematosus patients.

    PubMed

    Muñoz-Grajales, C; González, L A; Alarcón, G S; Acosta-Reyes, J

    2016-10-01

    The objective of this paper is to compare disease activity and clinical features at diagnosis in male and female patients with systemic lupus erythematosus (SLE). This was a cross-sectional study in which every male patient (n = 40) was matched with three female patients of the same age (±5 years) and racial/ethnic group; disease activity as per the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and disease manifestations at the time of diagnosis were compared. Alopecia and anti-Ro antibodies were more frequent in female patients. No statistically significant difference in any other disease characteristics was found. However, male gender was associated with a risk of severe disease activity at the time of diagnosis (as determined by SLEDAI ≥12 score) independent of age, racial/ethnic group, anti-Ro positivity or time to criteria accrual (OR: 3.11 95% CI, 1.09-8.92; p = 0.035). In newly diagnosed SLE patients, male gender is associated with higher disease activity despite the fact that male and female patients seem to experience similar overall disease manifestations. © The Author(s) 2016.

  20. Cardiac Atrophy and Heart Failure In Cancer

    PubMed Central

    Sweeney, Mark; Yiu, Angela

    2017-01-01

    Functional changes in the heart in patients with cancer can be a result of both the disease itself and various cancer therapies, and limiting cardiac damage has become an increasingly important issue as survival rates in patients with cancer have improved. Processes involved in cancer-induced cardiac atrophy may include cardiomyocyte atrophy and apoptosis, decreased protein synthesis, increased autophagy and proteolysis via the ubiquitin-proteosome system. Further to direct effects of malignancy on the heart, several chemotherapeutic agents are known to affect the myocardium, in particular the anthracyclines. The aim of this report is to review the effects of cancer and cancer treatment on the heart and what is known about the underlying mechanisms. Furthermore, clinical strategies to limit and treat cancer-associated cardiac atrophy are discussed, emphasising the benefit of a multidisciplinary approach by cardiologists and oncologists to optimise models of care to improve outcomes for patients with cancer. PMID:28785478

  1. Cardiac Atrophy and Heart Failure In Cancer.

    PubMed

    Sweeney, Mark; Yiu, Angela; Lyon, Alexander R

    2017-04-01

    Functional changes in the heart in patients with cancer can be a result of both the disease itself and various cancer therapies, and limiting cardiac damage has become an increasingly important issue as survival rates in patients with cancer have improved. Processes involved in cancer-induced cardiac atrophy may include cardiomyocyte atrophy and apoptosis, decreased protein synthesis, increased autophagy and proteolysis via the ubiquitin-proteosome system. Further to direct effects of malignancy on the heart, several chemotherapeutic agents are known to affect the myocardium, in particular the anthracyclines. The aim of this report is to review the effects of cancer and cancer treatment on the heart and what is known about the underlying mechanisms. Furthermore, clinical strategies to limit and treat cancer-associated cardiac atrophy are discussed, emphasising the benefit of a multidisciplinary approach by cardiologists and oncologists to optimise models of care to improve outcomes for patients with cancer.

  2. Method and system for the diagnosis of disease using retinal image content and an archive of diagnosed human patient data

    DOEpatents

    Tobin, Kenneth W; Karnowski, Thomas P; Chaum, Edward

    2013-08-06

    A method for diagnosing diseases having retinal manifestations including retinal pathologies includes the steps of providing a CBIR system including an archive of stored digital retinal photography images and diagnosed patient data corresponding to the retinal photography images, the stored images each indexed in a CBIR database using a plurality of feature vectors, the feature vectors corresponding to distinct descriptive characteristics of the stored images. A query image of the retina of a patient is obtained. Using image processing, regions or structures in the query image are identified. The regions or structures are then described using the plurality of feature vectors. At least one relevant stored image from the archive based on similarity to the regions or structures is retrieved, and an eye disease or a disease having retinal manifestations in the patient is diagnosed based on the diagnosed patient data associated with the relevant stored image(s).

  3. Neuroblastoma in a Patient With Spinal Muscular Atrophy Type I: Is It Just a Coincidence?

    PubMed

    Sag, Erdal; Sen, Hilal Susam; Haliloglu, Goknur; Yalcin, Bilgehan; Kutluk, Tezer

    2015-07-01

    Spinal muscular atrophy is an autosomal recessive disorder characterized by progressive degeneration of anterior horn cells of the spinal cord resulting in hypotonia, skeletal muscle atrophy, and weakness. Herein, we report a 4-month-old male infant who presented to our hospital with an abdominal mass that was diagnosed as neuroblastoma and spinal muscular atrophy type I. We would like to discuss the course and differential diagnosis with an algorithm leading to the diagnosis in this peculiar patient. To our knowledge, coexistence of spinal muscular atrophy type I and neuroblastoma is defined for the first time in the literature. © The Author(s) 2014.

  4. Pax2 expression in simultaneously diagnosed WHO and EIN classification systems.

    PubMed

    Joiner, Amy K; Quick, Charles M; Jeffus, Susanne K

    2015-01-01

    PAX2 has been cited as a technically robust biomarker which nicely delineates precancerous lesions of the endometrium when the endometrial intraepithelial neoplasia (EIN) classification scheme is used. Its utility in distinguishing between atypical and nonatypical hyperplasia when applied within the 1994 World Health Organization classification system is questionable. The purpose of this study was to evaluate PAX2 in a side by side comparison of its staining patterns in a series of endometrial samples that were classified using both systems. A total of 108 precancerous endometrial cases were identified, of which 30 cases were deemed nonhyperplastic by consensus agreement and 11 cases lost the tissue of interest on deeper sections. The remaining 67 cases were categorized according to the 1994 World Health Organization criteria and EIN scheme by 2 gynecologic pathologists. PAX2 staining was scored in lesional tissue as normal or altered (lost, increased, or decreased) compared with nonlesional background. The most common pattern of alteration was complete loss of nuclear PAX2 staining (86.3%) followed by decreased staining (11.3%) and markedly increased staining (2.3%). PAX2 alterations correlated well with EIN diagnoses (33/36, 92%) compared with benign hyperplasia (2/13, 15%) but were less useful when the 1994 World Health Organization classification system was applied (PAX2 alteration in 22/25 (88%) of atypical hyperplasia cases versus 16/25 (64%) of nonatypical hyperplasia cases). Forty-five percent of follow-up hysterectomies with a previous PAX2-altered biopsy case harbored adenocarcinoma. In conclusion, PAX2 may be a helpful adjunct stain and training tool when the features of atypical hyperplasia/EIN are in question.

  5. Angioimmunoblastic lymphadenopathy, sulphasalazine exposure and villous atrophy.

    PubMed Central

    Smith, M. A.; Steele, P. R.; Youngs, G. R.

    1985-01-01

    A woman with inflammatory lesions in the terminal ileum was treated with sulphasalazine. Nine months later she developed angioimmunoblastic lymphadenopathy and was found to have intestinal villous atrophy. Her systemic illness partially responded to oral steroids but a gluten free diet restored clinical and biochemical well being coincident with a return of her villous pattern. PMID:2862622

  6. Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases

    PubMed Central

    Smola, Malgorzata; Vandamme, Thierry; Sokolowski, Adam

    2008-01-01

    The purpose of this review is to discuss the impact of nanocarriers administered by pulmonary route to treat and to diagnose respiratory and non respiratory diseases. Indeed, during the past 10 years, the removal of chlorofluorocarbon propellants from industrial and household products intended for the pulmonary route has lead to the developments of new alternative products. Amongst these ones, on one hand, a lot of attention has been focused to improve the bioavailability of marketed drugs intended for respiratory diseases and to develop new concepts for pulmonary administration of drugs and, on the other hand, to use the pulmonary route to administer drugs for systemic diseases. This has led to some marketed products through the last decade. Although the introduction of nanotechnology permitted to step over numerous problems and to improve the bioavailability of drugs, there are, however, unresolved delivery problems to be still addressed. These scientific and industrial innovations and challenges are discussed along this review together with an analysis of the current situation concerning the industrial developments. PMID:18488412

  7. [Nursing diagnoses and outcomes related to the circulatory-system terms (ICNP®) represented in an ontology].

    PubMed

    Cubas, Marcia Regina; Brondani, Arianny Macedo; Malucelli, Andreia

    2013-10-01

    The aim of the present study was to develop titles of Nursing Diagnoses and Outcomes (ND/NO) through the relationship between the terms of the Focus axis, limited to the Circulatory System Process, and the terms of other ICNP® axes and to integrate these terms into an ontology. Titles were developed linking 17 terms of the focus axis, which were evaluated by expert nurses in five Brazilian cities. Titles whose use concordance was above 0.80 were included in the ontology. In total, 89 titles for ND/NO were supported in the literature, and 19 were not supported; 37 were assessed as eligible for use in healthcare practice and were included in the ontology. The construction of ND/NO titles based on the ICNP® and using a formal representation of knowledge is a task that requires deepening concepts used for nursing and adequate classification revisions. The elaborated titles will facilitate the composition of diagnostics that are more consistent with practice.

  8. Using MERRA Gridded Innovations for Quantifying Uncertainties in Analysis Fields and Diagnosing Observing System Inhomogeneities

    NASA Technical Reports Server (NTRS)

    da Silva, Arlindo; Redder, Christopher

    2010-01-01

    -likelihood estimates of background and observation errors, as well as global bias estimates. Starting with the joint PDF of innovations and analysis increments at observation locations we propose a technique for diagnosing bias among the observing systems, and document how these contextual biases have evolved during the satellite era covered by MERRA.

  9. Using MERRA Gridded Innovation for Quantifying Uncertainties in Analysis Fields and Diagnosing Observing System Inhomogeneities

    NASA Astrophysics Data System (ADS)

    da Silva, A.; Redder, C. R.

    2010-12-01

    -likelihood estimates of background and observation errors, as well as global bias estimates. Starting with the joint PDF of innovations and analysis increments at observation locations we propose a technique for diagnosing bias among the observing systems, and document how these contextual biases have evolved during the satellite era covered by MERRA.

  10. Diagnosing Snow and Sea Ice Radiative Forcing in the Community Earth System Model

    NASA Astrophysics Data System (ADS)

    Perket, J.; Flanner, M. G.

    2012-12-01

    Earth's albedo is evolving from changes in seasonal snow and sea-ice. Albedo feedback in climate models has been evaluated previously using the radiative kernel technique, where top-of-atmosphere (TOA) radiative fluxes associated with albedo change are calculated "offline" using pre-defined atmospheric states. This approach facilitates model intercomparisons, but can lead to inaccuracies associated with inconsistent surface and cloud states. We have incorporated a new diagnostic feature in the NCAR Community Earth System Model (CESM) that provides the instantaneous effect of land snow and sea ice on the TOA radiation budget at each time step. This diagnostic provides a precise measure of the radiative influence of model snow and sea ice, enables direct model comparison with observation-derived cryosphere radiative forcing (CrRF) estimates, and provides a means to evaluate the accuracy of the radiative kernel technique for diagnosing albedo feedback. Compared with observed northern hemisphere CrRF, we find that CESM produces a larger radiative effect for both land snow and sea ice. Preliminary analysis shows the snow radiative effect in the Northern Hemisphere to be higher in coupled ocean-land-atmosphere simulations compared to standalone land simulations forced with atmospheric reanalysis data. The same is true for ice when comparing the coupled system to offline ice simulations in the Southern Hemisphere. Differences are not as appreciable for sea ice in the North or snow in the South. Studies are planned to assess the accuracy of different radiative kernels, evaluate reasons for model-observation discrepancy in cryosphere radiative forcing, and quantify model changes in CrRF under different climate forcing scenarios.

  11. Chronic exposure to cerebrospinal fluid of multiple system atrophy in neuroblastoma and glioblastoma cells induces cytotoxicity via ER stress and autophagy activation

    PubMed Central

    Teng, Junfang; Zhang, Jiewen; Zhou, Shuang; Zhang, Ying; Wu, Erxi; Ding, Xuebing

    2015-01-01

    Oncogenesis and neurodegeneration share many common pathogenic pathways, involved in endoplastic reticulum (ER) stress, autophagy, DNA repair, and oxidative stress. However, mechanisms of cross-talking between oncogenesis and neurodegeneration are still unknown. Characterized by abnormal accumulation of α-synuclein (α-syn) aggregates in central nervous system (CNS), multiple system atrophy (MSA) is classified as α-synucleinopathy. Rapidly emerging evidence suggests that ‘prion-like propagation’ of α-syn aggregates in the regional spread of CNS leads to the progression of α-synucleinopathy. Whether cerebrospinal fluid (CSF) has deteriorating effects on neurogenic tumor cells and is involved in progression of α-synucleinopathy has not been explored. Here, we first show the cytotoxic effects of MSA-CSF on the neuroblastoma and glioblastoma cells and its underlying mechanism in vitro. Remarkably, MSA-CSF induced cytotoxicity via activating ER stress-associated apoptosis and autophagy in both SH-SY5Y and U251 cells. The result from in vivo systematic neuropathological analysis reveals that abnormally activated ER stress and autophagy were confined to substantia nigra and cerebellum in mouse CNS following MSA-CSF treatment. Specifically, dopamine neurons in substantia nigra and Purkinje cells in cerebellum cortex were degenerated in MSA-CSF-injected mice. Altogether, these findings demonstrate that MSA-CSF exerts cytotoxicities on nervous system neoplasms and accelerates the progression of synucleinopathies. PMID:25965819

  12. Automated analysis of whole skeletal muscle for muscular atrophy detection of ALS in whole-body CT images: preliminary study

    NASA Astrophysics Data System (ADS)

    Kamiya, Naoki; Ieda, Kosuke; Zhou, Xiangrong; Yamada, Megumi; Kato, Hiroki; Muramatsu, Chisako; Hara, Takeshi; Miyoshi, Toshiharu; Inuzuka, Takashi; Matsuo, Masayuki; Fujita, Hiroshi

    2017-03-01

    Amyotrophic lateral sclerosis (ALS) causes functional disorders such as difficulty in breathing and swallowing through the atrophy of voluntary muscles. ALS in its early stages is difficult to diagnose because of the difficulty in differentiating it from other muscular diseases. In addition, image inspection methods for aggressive diagnosis for ALS have not yet been established. The purpose of this study is to develop an automatic analysis system of the whole skeletal muscle to support the early differential diagnosis of ALS using whole-body CT images. In this study, the muscular atrophy parts including ALS patients are automatically identified by recognizing and segmenting whole skeletal muscle in the preliminary steps. First, the skeleton is identified by its gray value information. Second, the initial area of the body cavity is recognized by the deformation of the thoracic cavity based on the anatomical segmented skeleton. Third, the abdominal cavity boundary is recognized using ABM for precisely recognizing the body cavity. The body cavity is precisely recognized by non-rigid registration method based on the reference points of the abdominal cavity boundary. Fourth, the whole skeletal muscle is recognized by excluding the skeleton, the body cavity, and the subcutaneous fat. Additionally, the areas of muscular atrophy including ALS patients are automatically identified by comparison of the muscle mass. The experiments were carried out for ten cases with abnormality in the skeletal muscle. Global recognition and segmentation of the whole skeletal muscle were well realized in eight cases. Moreover, the areas of muscular atrophy including ALS patients were well identified in the lower limbs. As a result, this study indicated the basic technology to detect the muscle atrophy including ALS. In the future, it will be necessary to consider methods to differentiate other kinds of muscular atrophy as well as the clinical application of this detection method for early ALS

  13. Developing Expert System for Tuberculosis Diagnose to Support Knowledge Sharing in the Era of National Health Insurance System

    NASA Astrophysics Data System (ADS)

    Lidya, L.

    2017-03-01

    National Health Insurance has been implemented since 1st January 2014. A number of new policies have been established including multilevel referral system. The multilevel referral system classified health care center into three levels, it determined that the flow of patient treatment should be started from first level health care center. There are 144 kind of diseases that must be treat in the first level which mainly consists of general physicians. Unfortunately, competence of the physician in the first level may not fulfil the standard competence yet. To improved the physisians knowledge, government has created many events to accelerate knowledge sharing. However, it still needs times and many resources to give significan results. Expert system is kind of software that provide consulting services to non-expert users in accordance with the area of its expertise. It can improved effectivity and efficiency of knowledge sharing and learning. This research was developed a model of TB diagnose expert system which comply with the standard procedure of TB diagnosis and regulation. The proposed expert system has characteristics as follows provide facility to manage multimedia clinical data, supporting the complexity of TB diagnosis (combine rule-based and case-based expert system), interactive interface, good usability, multi-platform, evolutionary.

  14. Non-gaussianity of low frequency heart rate variability and sympathetic activation: lack of increases in multiple system atrophy and Parkinson disease.

    PubMed

    Kiyono, Ken; Hayano, Junichiro; Kwak, Shin; Watanabe, Eiichi; Yamamoto, Yoshiharu

    2012-01-01

    The correlates of indices of long-term ambulatory heart rate variability (HRV) of the autonomic nervous system have not been completely understood. In this study, we evaluated conventional HRV indices, obtained from the daytime (12:00-18:00) Holter recording, and a recently proposed non-Gaussianity index (λ; Kiyono et al., 2008) in 12 patients with multiple system atrophy (MSA) and 10 patients with Parkinson disease (PD), known to have varying degrees of cardiac vagal and sympathetic dysfunction. Compared with the age-matched healthy control group, the MSA patients showed significantly decreased HRV, most probably reflecting impaired vagal heart rate control, but the PD patients did not show such reduced variability. In both MSA and PD patients, the low-to-high frequency (LF/HF) ratio and the short-term fractal exponent α(1), suggested to reflect the sympathovagal balance, were significantly decreased, as observed in congestive heart failure (CHF) patients with sympathetic overdrive. In contrast, the analysis of the non-Gaussianity index λ showed that a marked increase in intermittent and non-Gaussian HRV observed in the CHF patients was not observed in the MSA and PD patients with sympathetic dysfunction. These findings provide additional evidence for the relation between the non-Gaussian intermittency of HRV and increased sympathetic activity.

  15. The value of the bulbocavernosus reflex and pudendal nerve somatosensory evoked potentials in distinguishing between multiple system atrophy and Parkinson's disease at an early stage.

    PubMed

    Cai, Z-Y; Niu, X-T; Pan, J; Ni, P-Q; Wang, X; Shao, B

    2017-09-01

    This study was designed to investigate the clinical value of the bulbocavernosus reflex (BCR) and pudendal nerve somatosensory evoked potentials (PSEPs) in the differential diagnosis between multiple system atrophy (MSA) and Parkinson's disease (PD) in early stage. A total of 31 patients with MSA, 45 patients with PD, and 60 healthy participants were included in this study. A Keypoint EMG/EP system was used for BCR and PSEP measurements. Electrophysiological parameters were collected for statistical analysis. The BCR elicitation rates were significantly lower in the patients with MSA than in the patients with PD (P<.05). Prolonged BCR latencies were found in the MSA group compared to the PD and control groups (P<.05). Bulbocavernosus reflex latencies were significantly prolonged in patients with MSA compared with PD patients showing early urogenital symptoms (P<.05). There was no significant difference in PSEP P41 latencies among the three groups (P=.434 in males, P=.948 in females). Both BCR and PSEP amplitudes were significantly lower in the MSA/PD group than in the control group (P<.001). Pudendal nerve damage is more severe in MSA than in PD. Prolonged BCR latency may be valuable for distinguishing between MSA and PD in the early stages. BCR and PSEP testing may also contribute to localized and qualitative diagnosis of the distribution of neurodegenerative pathologies in these two disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Color Doppler ultrasound criteria to diagnose varicoceles: correlation of a new scoring system with physical examination.

    PubMed

    Chiou, R K; Anderson, J C; Wobig, R K; Rosinsky, D E; Matamoros, A; Chen, W S; Taylor, R J

    1997-12-01

    Color Doppler ultrasound (CDU) diagnostic criteria for varicoceles are poorly defined, and the role of CDU in diagnosing varicoceles is controversial. The purpose of this study is to assess the diagnostic accuracy of CDU for varicoceles compared to physical examination. We prospectively studied 64 patients with CDU and collected the following data: maximum diameter of scrotal veins, the presence of a venous plexus, sum of the diameter of up to six veins of the plexus, and the duration and amplitude of flow change on Valsalva maneuver. To avoid interphysician variation, all patients were examined by one designated senior urologist with the sonographer remaining unaware of the findings. CDU parameters of 127 testis units in 64 patients were analyzed and compared to the physical findings. Fifty-nine testis units were positive and 57 units were negative for varicocele on physical examination. In 11 testis units, results of physical examination were inconclusive regarding the presence of varicocele. The commonly accepted CDU criterion for varicocele (maximal vein diameter of 3 mm or greater) had a sensitivity of 53% and specificity of 91% compared to physical examination. We developed a new scoring system incorporating the maximal venous diameter (score 0 to 3), the presence of a venous plexus and the sum of the diameters of veins in the plexus (score 0 to 3), and the change of flow on Valsalva maneuver (score 0 to 3). Using a total score of 4 or more to define the presence of CDU-positive varicocele, we observed a sensitivity of 93% and a specificity of 85% when compared to physical examination. All moderate to large varicoceles found on physical examination were positive by CDU diagnosis using the scoring system, but the same group had only a 68% positive rate by traditional CDU diagnostic criteria. Using the proposed new scoring system, CDU has been shown to be a reliable and accurate method of diagnosis for varicoceles compared to the current reference standard

  17. Progressive Hemifacial Atrophy--case report.

    PubMed

    Pinheiro, Thiago Pastor da Silva; Silva, Camila Camarinha da; Silveira, Carolina Souza Limeira da; Botelho, Patrícia Cristina Ereno; Pinheiro, Maria das Graças Rodriguez; Pinheiro, João de Jesus Viana

    2006-03-01

    Progressive Hemifacial Atrophy, also known as Parry-Romberg Syndrome, is an uncommon degenerative and poorly understood condition. It is characterized by a slow and progressive atrophy affecting one side of the face. The incidence and the cause of this alteration is unknown. A cerebral disturbance of fat metabolism has been proposed as a primary cause. This can be the result of a trophic malformation of Cervical Sympathetic Nervous System. Possible factors that are involved in the pathogenesis include trauma, viral infections, heredity, endocrine disturbances and auto-immunity, among others. The most common complications that appear in association to this health disorder are: trigeminal neuritis, facial paresthesia, severe headache and epilepsy, being this last one the most frequent complication of the Central Nervous System. Characteristically, the atrophy progresses slowly for several years and, soon after, it become stable. Now, plastic surgery with graft of autogenous fat can be performed, after stabilization of the disease, to correct the deformity. Orthodontic treatment can help in the correction of any associated malformation. The objective of this work is, through the presentation of a clinical case, to accomplish a literature review concerning general characteristics, etiology, physiopathology, differential diagnosis and treatment of progressive hemifacial atrophy.

  18. Treatment of vaginal atrophy.

    PubMed

    Domoney, Claudine

    2014-03-01

    Vaginal or vulvovaginal atrophy is a widespread but poorly recognized condition of peri- and post-menopausal women. It causes urogenital symptoms of dryness, reduced lubrication, itching, burning, irritable bladder symptoms and painful intercourse. This impacts quality of life and sexual health, but increases with time rather than reduces, as with most other menopausal symptoms. With early identification, treatments can improve these symptoms and reverse the physical changes. However, when embedded, bladder and sexual changes have occurred and these may be more difficult to remedy. Therefore, it is important to educate both healthcare professionals and women about these symptoms and advise on the range of interventions available.

  19. Spinal Muscular Atrophy.

    PubMed

    Kolb, Stephen J; Kissel, John T

    2015-11-01

    Spinal muscular atrophy is an autosomal-recessive disorder characterized by degeneration of motor neurons in the spinal cord and caused by mutations in the survival motor neuron 1 gene, SMN1. The severity of SMA is variable. The SMN2 gene produces a fraction of the SMN messenger RNA (mRNA) transcript produced by the SMN1 gene. There is an inverse correlation between SMN2 gene copy number and clinical severity. Clinical management focuses on multidisciplinary care. Preclinical models of SMA have led to an explosion of SMA clinical trials that hold great promise of effective therapy in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. The effects of Capn1 gene inactivation on skeletal muscle growth, development, and atrophy, and the compensatory role of other proteolytic systems.

    PubMed

    Kemp, C M; Oliver, W T; Wheeler, T L; Chishti, A H; Koohmaraie, M

    2013-07-01

    Myofibrillar protein turnover is a key component of muscle growth and degeneration, requiring proteolytic enzymes to degrade the skeletal muscle proteins. The objective of this study was to investigate the role of the calpain proteolytic system in muscle growth development using μ-calpain knockout (KO) mice in comparison with control wild-type (WT) mice, and evaluate the subsequent effects of silencing this gene on other proteolytic systems. No differences in muscle development between genotypes were observed during the early stages of growth due to the up regulation of other proteolytic systems. The KO mice showed significantly greater m-calpain protein abundance (P < 0.01) and activity (P < 0.001), and greater caspase 3/7 activity (P < 0.05). At 30 wk of age, KO mice showed increased protein:DNA (P < 0.05) and RNA:DNA ratios (P < 0.01), greater protein content (P < 0.01) at the expense of lipid deposition (P < 0.05), and an increase in size and number of fast-twitch glycolytic muscle fibers (P < 0.05), suggesting that KO mice exhibit an increased capacity to accumulate and maintain protein in their skeletal muscle. Also, expression of proteins associated with muscle regeneration (neural cell adhesion molecule and myoD) were both reduced in the mature KO mice (P < 0.05 and P < 0.01, respectively), indicating less muscle regeneration and, therefore, less muscle damage. These findings indicate the concerted action of proteolytic systems to ensure muscle protein homeostasis in vivo. Furthermore, these data contribute to the existing evidence of the importance of the calpain system's involvement in muscle growth, development, and atrophy. Collectively, these data suggest that there are opportunities to target the calpain system to promote the growth and/or restoration of skeletal muscle mass.

  1. Predictive efficacy of the 2014 International Society of Urological Pathology Gleason grading system in initially diagnosed metastatic prostate cancer

    PubMed Central

    Sun, Guang-Xi; Shen, Peng-Fei; Zhang, Xing-Ming; Gong, Jing; Gui, Hao-Jun; Shu, Kun-Peng; Liu, Jiang-Dong; Zhao, Jinge; Yang, Yao-Jing; Chen, Xue-Qin; Chen, Ni; Zeng, Hao

    2017-01-01

    We compared the predictive ability of the 2014 and 2005 Gleason grading systems in 568 patients initially diagnosed with metastatic prostate cancer (PCa). Outcomes included the duration of castration-resistant prostate cancer-free survival (CFS) and overall survival (OS). Univariate analyses and log-rank tests were used to identify prognosis indicators and assess univariable differences in CFS and OS in Gleason score (GS) groups. Cox proportional hazards and area under the curves of receiver operator characteristics methods were used to evaluate the predictive efficacy of the 2005 and 2014 ISUP grading systems. Univariate analyses showed that the 2005 and 2014 grading systems were prognosticators for CFS and OS; both systems could distinguish the clinical outcome of patients with GS 6, GS 7, and GS 8–10. Using the 2014 criteria, no statistical differences in patient survival were observed between GS 3 + 4 and GS 4 + 3 or GS 8 and GS 9–10. The predictive ability of the 2014 and 2005 grading systems was comparable for CFS and OS (P = 0.321). However, the 2014 grading system did not exhibit superior predictive efficacy in patients initially diagnosed with PCa and bone metastasis; trials using larger cohorts are required to confirm its predictive value. To the best of our knowledge, ours is the first study to compare the 2005 and 2014 grading systems in initially diagnosed PCa with bone metastasis. At present, we recommend that both systems should be used to predict the prognosis of patients with metastatic PCa. PMID:27569001

  2. Diagnosing ALS

    MedlinePlus

    ... that a person diagnosed with ALS seek a second opinion from an ALS "expert" - someone who diagnoses and treats many ALS patients and has training in this medical specialty. The ALS Association maintains a list of recognized experts in the field of ALS. See ALS Association Certified Centers of ...

  3. Association between diagnosed diabetes and serious psychological distress among U.S. adults: the Behavioral Risk Factor Surveillance System, 2007.

    PubMed

    Li, Chaoyang; Ford, Earl S; Zhao, Guixiang; Strine, Tara W; Dhingra, Satvinder; Barker, Lawrence; Berry, Joyce T; Mokdad, Ali H

    2009-06-01

    To estimate the prevalence of serious psychological distress (SPD) according to diabetes status and to assess the association of diabetes-related risks and conditions with SPD among U.S. adults. We analyzed data from the Behavioral Risk Factor Surveillance System, 2007. SPD was determined by a score of > or = 13 on the Kessler-6 scale. We used log-binomial regression analysis to estimate prevalence ratios (PRs) and 95 % confidence intervals (CIs). We estimated the prevalence of SPD to be 7.6 % and 3.6 % among U.S. adults with and without diagnosed diabetes (unadjusted PR: 2.09; 95 % CI: 1.87, 2.34). The association of diagnosed diabetes with SPD was attenuated after adjustments for potential confounding effects of cardiovascular risk factors and cardiovascular comorbid conditions (adjusted PR, 1.12; 95 % CI: 0.99, 1.27). Significant correlates of SPD among persons with diagnosed diabetes were young age, low education levels, low household income, obesity, current smoking, no leisure-time physical activity, presence of one or more micro- or macro-vascular complications, and disability. The crude prevalence of SPD among adults with diagnosed diabetes was twice as high as that among those without diabetes. The increased prevalence of SPD may be accounted for by the excessive rates of cardiovascular risks and comorbid conditions among people with diagnosed diabetes.

  4. Posterior Cortical Atrophy

    PubMed Central

    Crutch, Sebastian J; Lehmann, Manja; Schott, Jonathan M; Rabinovici, Gil D; Rossor, Martin N; Fox, Nick C

    2013-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that is characterized by a progressive decline in visuospatial, visuoperceptual, literacy and praxic skills. The progressive neurodegeneration affecting parietal, occipital and occipito-temporal cortices which underlies PCA is attributable to Alzheimer's disease (AD) in the majority of patients. However, alternative underlying aetiologies including Dementia with Lewy Bodies (DLB), corticobasal degeneration (CBD) and prion disease have also been identified, and not all PCA patients have atrophy on clinical imaging. This heterogeneity has led to diagnostic and terminological inconsistencies, caused difficulty comparing studies from different centres, and limited the generalizability of clinical trials and investigations of factors driving phenotypic variability. Significant challenges remain in identifying the factors associated with both the selective vulnerability of posterior cortical regions and the young age of onset seen in PCA. Greater awareness of the syndrome and agreement over the correspondence between syndrome-and disease-level classifications are required in order to improve diagnostic accuracy, research study design and clinical management. PMID:22265212

  5. Collagenous colitis associated with small intestinal villous atrophy.

    PubMed Central

    Hamilton, I; Sanders, S; Hopwood, D; Bouchier, I A

    1986-01-01

    Two patients diagnosed as having small intestinal hyperplastic villous atrophy and being treated with a gluten free diet were investigated because of persistent watery diarrhoea. Both were found to have collagenous colitis. Previous reports of this condition have emphasised the presence of normal small intestinal mucosal architecture and the association of collagenous colitis with intestinal villous atrophy has not previously been reported. Both cases responded to oral steroid therapy, but not to other previously recommended treatment regimens. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:3792923

  6. Inflammation, atrophy, and gastric cancer

    PubMed Central

    Fox, James G.; Wang, Timothy C.

    2006-01-01

    The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world’s population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment. PMID:17200707

  7. [A case of an anti-Ma2 antibody-positive patient presenting with variable CNS symptoms mimicking multiple system atrophy with a partial response to immunotherapy].

    PubMed

    Shiraishi, Wataru; Iwanaga, Yasutaka; Yamamoto, Akifumi

    2015-01-01

    A 70-year-old man with a 5-month history of progressive bradykinesia of the bilateral lower extremities was admitted to our hospital. At the age of 64, he underwent proximal gastrectomy for gastric cancer. He also had a history of subacute combined degeneration of the spinal cord since the age of 67, which was successfully treated with vitamin B12 therapy. Four weeks before admission to our hospital, he admitted himself to his former hospital complaining of walking difficulty. Two weeks later, however, his symptoms progressed rapidly; he was immobilized for two weeks and did not respond to the vitamin therapy. On admission to our hospital, he showed moderate paralysis of the lower extremities, cog-wheel rigidity of the four extremities, and dystonic posture of his left hand. He also showed orthostatic hypotension and vesicorectal disorders. Blood examination and cerebrospinal fluid analysis revealed no remarkable abnormalities. Electroencephalography showed frontal dominant, high voltage, sharp waves. His brain and spinal MRI revealed no notable abnormalities. We suspected autoimmune disease and commenced one course of intravenous methylprednisolone therapy, resulting in improvement of the parkinsonism and orthostatic hypotension. Based on these results, we investigated possible neural antigens and detected anti-Ma2 antibody. In addition to limbic encephalitis, anti-Ma2 antibody-positive neural disorders are characterized by rapid eye movement sleep behavior disorders or parkinsonism. Here, we report an anti-Ma2 antibody positive patient presenting variable CNS symptoms mimicking multiple system atrophy, who responded to immunotherapy.

  8. Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson Disease, dementia with Lewy bodies, multiple system atrophy) from Alzheimer disease.

    PubMed

    Tateno, Fuyuki; Sakakibara, Ryuji; Kawai, Takayuki; Kishi, Masahiko; Murano, Takeyoshi

    2012-01-01

    We examined the utility of quantification of α-synuclein (SNCA) in the cerebrospinal fluid (CSF) to differentiate patients with Alzheimer disease (AD), dementia with Lewy bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA). Thirty-seven patients were divided into 4 age-matched and sex-matched clinical groups: AD (n = 9), DLB (n = 6), PD (n = 11), and MSA (n = 11). Eleven subjects served as neurological disease controls. The total of 48 subjects included 27 men and 21 women, aged 66.5 ± 11.4 years. We performed a solid-phase sandwich enzyme-linked immunosorbent assay, which enables the sensitive quantification of CSF SNCA. In comparison with controls, CSF SNCA levels in AD were significantly higher (P < 0.05). CSF SNCA levels in PD (P < 0.001), DLB (P < 0.01), and MSA (P < 0.05) were all significantly lower than those in AD. However, CSF SNCA levels did not differ significantly among the 3 synucleinopathies. The results of the present study suggest that quantification of CSF SNCA helps in the differentiation of synucleinopathies (PD, DLB, and MSA) from AD. However, CSF SNCA levels did not differ significantly among the 3 synucleinopathies.

  9. The Utility of Post-Void Residual Volume versus Sphincter Electromyography to Distinguish between Multiple System Atrophy and Parkinson’s Disease

    PubMed Central

    Yamamoto, Tatsuya; Asahina, Masato; Yamanaka, Yoshitaka; Uchiyama, Tomoyuki; Hirano, Shigeki; Fuse, Miki; Koga, Yasuko; Sakakibara, Ryuji; Kuwabara, Satoshi

    2017-01-01

    Objective To determine the ability of sphincter electromyography (EMG) and post-void residual urine volume (PVR) during a free-flow study and a pressure-flow study (PFS) for distinguishing multiple system atrophy (MSA) from Parkinson’s disease (PD). Methods We retrospectively reviewed 241 case records; both urodynamic study and sphincter EMG were performed in patients with MSA (n = 147) and PD (n = 94). Results There was a statistically significant difference (p < 0.01) in the mean PVR during the free-flow study (113.1 ± 7.5 mL in MSA and 40.4 ± 3.8 mL in PD), mean PVR during PFS (230.1 ± 12.6 mL in MSA and 71.7 ± 6.6 mL in PD), and mean duration of MUP for sphincter EMG (9.3 ± 0.1 ms in MSA and 7.7 ± 0.1 ms in PD). The area under the curve used for differentiating MSA from PD was 0.79 and 0.73 for PVR during PFS and the free-flow study, respectively. There was a mean duration of 0.69 ms for the sphincter EMG. Conclusions The present results suggested that PVR was more appropriate than sphincter EMG for differentiating MSA from PD. PMID:28060892

  10. Comparison of brain MRI and 18F-FDG PET in the differential diagnosis of multiple system atrophy from Parkinson's disease.

    PubMed

    Kwon, Kyum-Yil; Choi, Choong G; Kim, Jae S; Lee, Myoung C; Chung, Sun J

    2007-12-01

    To investigate the diagnostic value of brain magnetic resonance image (MRI) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the differentiation of multiple system atrophy (MSA) from Parkinson's disease (PD). Thirty-five patients with MSA (23 MSA-P and 12 MSA-C) and 17 patients with PD were included in this study. Overall correct diagnosis rates between clinical and imaging diagnosis among MSA-P, MSA-C, and PD patients were 80% for visual MRI analysis, 88.5% for visual (18)F-FDG PET analysis, and 84.3% for SPM-supported analysis of (18)F-FDG PET. The sensitivity of brain MRI, and visual and SPM analysis of (18)F-FDG PET in differentiating MSA from PD was 72.7%, 90.9%, and 95.5%, respectively, the specificity was 100% for each imaging analysis, the positive predictive value was 100% for each imaging analysis, and the negative predictive value was 60%, 81.8%, and 90%, respectively. Our results suggest that brain MRI and (18)F-FDG PET are diagnostically useful in differentiating MSA (MSA-P and MSA-C) from PD, and indicate that (18)F-FDG PET has a tendency toward higher sensitivity compared to brain MRI, but a larger longitudinal study including pathological data will be required to confirm our findings.

  11. Redox control of skeletal muscle atrophy

    PubMed Central

    Powers, Scott K.; Morton, Aaron B.; Ahn, Bumsoo; Smuder, Ashley J.

    2016-01-01

    Skeletal muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal muscles is important to support overall health of the body. Prolonged periods of muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal muscle atrophy. An excessive loss of muscle mass is associated with a poor prognosis in several diseases and significant muscle weakness impairs the quality of life. The skeletal muscle atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and muscle atrophy. More specifically, this review will debate the sources of oxidant production in skeletal muscle undergoing atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown. PMID:26912035

  12. Diagnosing Flu

    MedlinePlus

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine/Variant Pandemic Other Diagnosing Flu Questions & Answers Language: English (US) Español Recommend ...

  13. Validation of a novel sleep-monitoring system for diagnosing obstructive sleep apnea: A comparison with polysomnography

    PubMed Central

    Meng, Lili; Xu, Huajun; Guan, Jian; Yi, Hongliang; Wu, Hongmin; Yin, Shankai

    2016-01-01

    Overnight polysomnography (PSG) is currently the gold standard for diagnosing obstructive sleep apnea (OSA); however, it is time-consuming, expensive and uncomfortable for the patient. A micromovement sensitive mattress (MSM) sleep-monitoring system was developed as an alternative to PSG, however, there has yet to be a study verifying the accuracy of diagnosing OSA with this device. Therefore, the present study assessed the validity of the MSM sleep-monitoring system. Chinese Han participants who were suspected of having OSA were recruited between June 2013 and June 2014. The MSM sleep-monitoring system and PSG were utilized simultaneously overnight on each subject. The apnea-hypopnea index (AHI) was measured by the MSM sleep-monitoring system (AHIMSM) and compared with that determined by PSG (AHIPSG), revealing a significant correlation between the two values (r=0.97, P<0.001). Bland-Altman plots also indicated good agreement (97%) between MSM and PSG. Using an AHIPSG cut-off of ≥5, ≥15 and ≥30 events/h, the sensitivity (specificity) of detecting an AHIMSM of ≥5, ≥15, and ≥30 events/h were 94.9 (100%), 89.9 (96.9%) and 90.3% (94.9%), respectively. The areas under the receiver operating characteristic curve, which were used to differentiate an AHIPSG of ≥5, ≥15 and ≥30 events/h in clinically diagnosed OSA, were 0.984, 0.982 and 0.980, respectively. Thus, the MSM sleeping system may accurately diagnose OSA in the Chinese Han population. Further community-based studies with larger sample sizes are warranted to confirm the validity of this MSM sleeping system. PMID:27882098

  14. Validation of a novel sleep-monitoring system for diagnosing obstructive sleep apnea: A comparison with polysomnography.

    PubMed

    Meng, Lili; Xu, Huajun; Guan, Jian; Yi, Hongliang; Wu, Hongmin; Yin, Shankai

    2016-11-01

    Overnight polysomnography (PSG) is currently the gold standard for diagnosing obstructive sleep apnea (OSA); however, it is time-consuming, expensive and uncomfortable for the patient. A micromovement sensitive mattress (MSM) sleep-monitoring system was developed as an alternative to PSG, however, there has yet to be a study verifying the accuracy of diagnosing OSA with this device. Therefore, the present study assessed the validity of the MSM sleep-monitoring system. Chinese Han participants who were suspected of having OSA were recruited between June 2013 and June 2014. The MSM sleep-monitoring system and PSG were utilized simultaneously overnight on each subject. The apnea-hypopnea index (AHI) was measured by the MSM sleep-monitoring system (AHIMSM) and compared with that determined by PSG (AHIPSG), revealing a significant correlation between the two values (r=0.97, P<0.001). Bland-Altman plots also indicated good agreement (97%) between MSM and PSG. Using an AHIPSG cut-off of ≥5, ≥15 and ≥30 events/h, the sensitivity (specificity) of detecting an AHIMSM of ≥5, ≥15, and ≥30 events/h were 94.9 (100%), 89.9 (96.9%) and 90.3% (94.9%), respectively. The areas under the receiver operating characteristic curve, which were used to differentiate an AHIPSG of ≥5, ≥15 and ≥30 events/h in clinically diagnosed OSA, were 0.984, 0.982 and 0.980, respectively. Thus, the MSM sleeping system may accurately diagnose OSA in the Chinese Han population. Further community-based studies with larger sample sizes are warranted to confirm the validity of this MSM sleeping system.

  15. Hypocupremia: A Possible Association with Late Cortical Cerebellar Atrophy

    PubMed Central

    Mittal, Shivam Om; Machado, Duarte G.

    2014-01-01

    Background We report a patient, diagnosed with late cortical cerebellar atrophy, who had persistent low serum copper levels. Case report A 48-year-old male developed progressive difficulty with balance, frequent falls, and dysarthric speech, which worsened over a short time span. He had an extensive ataxia work-up, which was unremarkable except for persistent low serum copper levels despite adequate supplementation. Magnetic resonance imaging of the brain showed marked cerebellar atrophy. The patient experienced progressive worsening of symptoms, which did not improve with either oral or parenteral copper supplementation. Discussion To our knowledge, ours is the first case report of late cortical cerebellar atrophy in the setting of low serum copper levels. The current report should trigger further research in mechanisms leading to copper deficiency and its possible role in cerebellar disease. PMID:25247109

  16. Transcriptional profile of a myotube starvation model of atrophy

    NASA Technical Reports Server (NTRS)

    Stevenson, Eric J.; Koncarevic, Alan; Giresi, Paul G.; Jackman, Robert W.; Kandarian, Susan C.

    2005-01-01

    Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

  17. Transcriptional profile of a myotube starvation model of atrophy

    NASA Technical Reports Server (NTRS)

    Stevenson, Eric J.; Koncarevic, Alan; Giresi, Paul G.; Jackman, Robert W.; Kandarian, Susan C.

    2005-01-01

    Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

  18. Systemic, postsymptomatic antisense oligonucleotide rescues motor unit maturation delay in a new mouse model for type II/III spinal muscular atrophy

    PubMed Central

    Bogdanik, Laurent P.; Osborne, Melissa A.; Davis, Crystal; Martin, Whitney P.; Austin, Andrew; Rigo, Frank; Bennett, C. Frank; Lutz, Cathleen M.

    2015-01-01

    Clinical presentation of spinal muscular atrophy (SMA) ranges from a neonatal-onset, very severe disease to an adult-onset, milder form. SMA is caused by the mutation of the Survival Motor Neuron 1 (SMN1) gene, and prognosis inversely correlates with the number of copies of the SMN2 gene, a human-specific homolog of SMN1. Despite progress in identifying potential therapies for the treatment of SMA, many questions remain including how late after onset treatments can still be effective and what the target tissues should be. These questions can be addressed in part with preclinical animal models; however, modeling the array of SMA severities in the mouse, which lacks SMN2, has proven challenging. We created a new mouse model for the intermediate forms of SMA presenting with a delay in neuromuscular junction maturation and a decrease in the number of functional motor units, all relevant to the clinical presentation of the disease. Using this new model, in combination with clinical electrophysiology methods, we found that administering systemically SMN-restoring antisense oligonucleotides (ASOs) at the age of onset can extend survival and rescue the neurological phenotypes. Furthermore, these effects were also achieved by administration of the ASOs late after onset, independent of the restoration of SMN in the spinal cord. Thus, by adding to the limited repertoire of existing mouse models for type II/III SMA, we demonstrate that ASO therapy can be effective even when administered after onset of the neurological symptoms, in young adult mice, and without being delivered into the central nervous system. PMID:26460027

  19. APOE ε4 is associated with disproportionate progressive hippocampal atrophy in AD.

    PubMed

    Manning, Emily N; Barnes, Josephine; Cash, David M; Bartlett, Jonathan W; Leung, Kelvin K; Ourselin, Sebastien; Fox, Nick C

    2014-01-01

    To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates. MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into "progressors" (MCI-P) if diagnosed with AD within 36 months or "stable" (MCI-S) if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated. Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P. These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD.

  20. Smart cloud system with image processing server in diagnosing brain diseases dedicated for hospitals with limited resources.

    PubMed

    Fahmi, Fahmi; Nasution, Tigor H

    2017-01-19

    The use of medical imaging in diagnosing brain disease is growing. The challenges are related to the big size of data and complexity of the image processing. High standard of hardware and software are demanded, which can only be provided in big hospitals. Our purpose was to provide a smart cloud system to help diagnosing brain diseases for hospital with limited infrastructure. The expertise of neurologists was first implanted in cloud server to conduct an automatic diagnosis in real time using image processing technique developed based on ITK library and web service. Users upload images through website and the result, in this case the size of tumor was sent back immediately. A specific image compression technique was developed for this purpose. The smart cloud system was able to measure the area and location of tumors, with average size of 19.91 ± 2.38 cm2 and an average response time 7.0 ± 0.3 s. The capability of the server decreased when multiple clients accessed the system simultaneously: 14 ± 0 s (5 parallel clients) and 27 ± 0.2 s (10 parallel clients). The cloud system was successfully developed to process and analyze medical images for diagnosing brain diseases in this case for tumor.

  1. Rates of cerebral atrophy differ in different degenerative pathologies

    PubMed Central

    Whitwell, Jennifer L; Jack, Clifford R.; Parisi, Joseph E.; Knopman, David S.; Boeve, Bradley F.; Petersen, Ronald C.; Ferman, Tanis J.; Dickson, Dennis W.; Josephs, Keith A.

    2009-01-01

    SUMMARY Neurodegenerative disorders are pathologically characterized by the deposition of abnormal proteins in the brain. It is likely that future treatment trials will target the underlying protein biochemistry and it is therefore increasingly important to be able to distinguish between different pathologies during life. The aim of this study was to determine whether rates of brain atrophy differ in neurodegenerative dementias that vary by pathological diagnoses and characteristic protein biochemistry. Fifty-six autopsied subjects were identified with a clinical diagnosis of dementia and two serial head MRI. Subjects were subdivided based on pathological diagnoses into Alzheimer's disease (AD), dementia with Lewy bodies (DLB), mixed AD/DLB, frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes (FTLD-U), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Twenty-five controls were matched by age, gender, and scan interval, to the study cohort. The boundary-shift integral was used to calculate change over time in whole brain (BBSI) and ventricular volume (VBSI). All BSI results were annualized by adjusting for scan interval. The rates of whole brain atrophy and ventricular expansion were significantly increased compared to controls in the AD, mixed AD/DLB, FTLD-U, CBD and PSP groups. However, atrophy rates in the DLB group were not significantly different from control rates of atrophy. The largest rates of atrophy were observed in the CBD group which had a BBSI of 2.3% and VBSI of 16.2%. The CBD group had significantly greater rates of BBSI and VBSI than the DLB, mixed AD/DLB, AD and PSP groups, with a similar trend observed when compared to the FTLD-U group. The FTLD-U group showed the next largest rates with a BBSI of 1.7% and VBSI of 9.6% which were both significantly greater than the DLB group. There was no significant difference in the rates of atrophy between the AD, mixed AD/DLB and PSP groups, which all showed

  2. Brain atrophy in frontotemporal dementia.

    PubMed Central

    Frisoni, G B; Beltramello, A; Geroldi, C; Weiss, C; Bianchetti, A; Trabucchi, M

    1996-01-01

    OBJECTIVES--To evaluate the pattern of regional brain atrophy in patients with frontotemporal dementia by comparing it with that in patients with Alzheimer's disease and normal controls. METHODS--Fourteen patients with frontotemporal dementia, 13 with moderate, and 33 with mild Alzheimer's disease, and 31 controls were studied. Atrophy was evaluated with linear measures in the anterior brain, medial temporal lobe, and hippocampal formation regions using MRI. RESULTS--Patients with frontotemporal dementia had greater atrophy in the anterior brain regions than patients with Alzheimer's disease or controls. Atrophy of the hippocampal formation, which best discriminates Alzheimer's disease from controls, was present also in patients with frontotemporal dementia. By contrast, atrophy of the medial temporal lobe, which is also present in Alzheimer's disease, was absent in frontotemporal dementia. CONCLUSION--A pattern of atrophy in the frontal lobes and hippocampal formation with sparing of the medial temporal lobe might be distinctive of frontotemporal dementia. Hippocampal involvement might not be specific for Alzheimer's disease and specific patterns of atrophy might be distinctive of some forms of degenerative dementia. Images PMID:8708683

  3. The Significance of Bronchial Atrophy

    PubMed Central

    Maisel, John C.; Silvers, G. Wayne; George, Marlyce S.; Dart, Gladys A.; Petty, Thomas L.; Mitchell, Roger S.

    1972-01-01

    In a 4-year period, 196 lungs from patients with and without chronic obstructive pulmonary disease were examined postmortem for the presence of atrophy in segmental and subsegmental bronchi. As a result of simultaneous postmortem spirometry, cinefluorobronchography and partitioning of airways resistance, plus later assessment of anatomic emphysema, bronchial atrophy emerges as only one of at least three factors usually cooperating in production of abnormal expiratory airway collapse. In selected cases, bronchial atrophy appears to be an important contributor to expiratory airways obstruction. ImagesFig 1 PMID:5021107

  4. Concordance between Patient Self-Reports and Claims Data on Clinical Diagnoses, Medication Use, and Health System Utilization in Taiwan

    PubMed Central

    Wu, Chi-Shin; Lai, Mei-Shu; Gau, Susan Shur-Fen; Wang, Sheng-Chang; Tsai, Hui-Ju

    2014-01-01

    Purpose The aim of this study was to evaluate the concordance between claims records in the National Health Insurance Research Database and patient self-reports on clinical diagnoses, medication use, and health system utilization. Methods In this study, we used the data of 15,574 participants collected from the 2005 Taiwan National Health Interview Survey. We assessed positive agreement, negative agreement, and Cohen's kappa statistics to examine the concordance between claims records and patient self-reports. Results Kappa values were 0.43, 0.64, and 0.61 for clinical diagnoses, medication use, and health system utilization, respectively. Using a strict algorithm to identify the clinical diagnoses recorded in claims records could improve the negative agreement; however, the effect on positive agreement and kappa was diverse across various conditions. Conclusion We found that the overall concordance between claims records in the National Health Insurance Research Database and patient self-reports in the Taiwan National Health Interview Survey was moderate for clinical diagnosis and substantial for both medication use and health system utilization. PMID:25464005

  5. Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson's disease and multiple system atrophy in a Chinese population.

    PubMed

    Chen, YongPing; Cao, Bei; Yang, Jing; Wei, QianQian; Ou, Ru Wei; Zhao, Bi; Song, Wei; Guo, XiaoYan; Shang, HuiFang

    2015-11-01

    Whether polymorphisms rs11856808 and rs9652490 of the Leucine-rich repeat and Ig domain containing, Nogo receptor-interacting protein-1 (LINGO1) gene, as well as rs10968280, rs13362909 and rs7033345 of the LINGO2 gene, increase the risk for Parkinson's disease (PD) is controversial. Considering the overlap of the clinical and pathological characteristics among PD and multiple system atrophy (MSA), we explored the associations between these five polymorphisms and PD and MSA in a Chinese population. A total of 1055 PD patients, 320 MSA patients, and 810 healthy controls (HCs) were genotyped for these five polymorphisms in LINGO1 and LINGO 2 using Sequenom iPLEX Assay technology. Moreover, after combining our results with available published data, a meta-analysis was conducted to investigate the associations between LINGO 1 rs11856808 and rs9652490 and the risk of PD. The frequency of the minor alleles "T" of LINGO1 rs11856808 was significantly lower in PD than that in HCs (p = 0.011, OR 0.89, 95 % CI 0.81-0.97), but not in MSA. Moreover, there were no significant differences in the minor allele frequency distributions of the other four polymorphisms between PD and HCs, and between MSA and HCs. The meta-analysis showed a lack of association of rs9652490 and PD, regardless of the genetic model or ethnic origin. However, the rs11856808 allele decreased the risk of PD in patients of Asian origin in a dominant genetic model. Our findings suggest that rs11856808 plays a protective role by decreasing the risk for PD, but not for MSA, in Asian population, the other four polymorphisms do not contribute to the risk for PD and MSA.

  6. Genetic Variants of SNCA Are Associated with Susceptibility to Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis or Multiple System Atrophy in a Chinese Population

    PubMed Central

    Ou, RuWei; Cao, Bei; Chen, XuePing; Zhao, Bi; Guo, XiaoYan; Yang, Yuan; Chen, Ke; Wu, Ying; Song, Wei; Shang, Hui-Fang

    2015-01-01

    Background The polymorphisms of α-synuclein (SNCA), rs3775444, rs3822086 and rs11931074 that are strongly associated with Parkinson’s disease (PD) in Caucasian populations, were examined in this study to elucidate the role of polymorphisms in different ethnic backgrounds. The possible associations of these three polymorphisms were also investigated in PD, amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) in a Chinese population based on the overlapping of clinical manifestations and pathological characteristics of these three neurodegenerative diseases. Methods A total of 1276 PD, 885 sporadic ALS (SALS), 364 MSA patients, and 846 healthy controls (HCs) were included. All subjects were genotyped for the three polymorphisms using Sequenom iPLEX Assay technology. Results Significant differences in the genotype distributions (p = 5.99E-06 and p = 4.98E-06, respectively) and the minor allele frequency (MAF) (p = 2.16E-06 and p = 2.15E-06, respectively) of SNCA rs3822086 (C) and rs11931074 (G) were observed between PD and HCs. However, no differences were found in the genotype distributions and MAF of SNCA rs3775444 (T) between PD and HCs. Haplotype that incorporated the three SNPs further strengthened the association with PD (best haplotype, p = 9.62E-005). No significant differences in the genotype distributions and MAF of the SNPs were found between SALS and HCs, MSA and HCs, and subgroups of PD and SALS. However, the MAF of SNCA rs3775444 (T) was significantly higher in MSA patients with frontal lobe dysfunction than MSA patients without dysfunction (p = 0.0002, OR 2.53, 95%CI: 1.55-4.15). Conclusion Our results suggest that the rs3822086 (C) allele and rs11931074 (G) allele in SNCA decrease the risk for PD, and SNCA rs11931074 may affect frontal lobe dysfunction of MSA in the Chinese population. However, these SNCA polymorphisms are not likely a common cause of SALS or MSA. PMID:26208350

  7. Intraventricular cerebrospinal fluid temperature analysis using MR diffusion-weighted imaging thermometry in Parkinson's disease patients, multiple system atrophy patients, and healthy subjects.

    PubMed

    Sumida, Kaoru; Sato, Noriko; Ota, Miho; Sakai, Koji; Nippashi, Yasumasa; Sone, Daichi; Yokoyama, Kota; Ito, Kimiteru; Maikusa, Norihide; Imabayashi, Etsuko; Matsuda, Hiroshi; Yamada, Kei; Murata, Miho; Kunimatsu, Akira; Ohtomo, Kuni

    2015-06-01

    We examined the temperature of the intraventricular cerebrospinal fluid (Tv) in patients with Parkinson's disease (PD) and those with multiple system atrophy (MSA) in comparison with healthy subjects, and we examined normal changes in this temperature with aging. Tv was estimated by magnetic resonance (MR) diffusion-weighted imaging (DWI) thermometry in 36 PD patients (19 males, 17 females), 34 MSA patients (17 males, 17 females), 64 age-matched controls (27 men, 37 women), and 114 all-age adult controls (47 men, 67 women; 28-89 years old). The volume of lateral ventricles was also estimated using FreeSurfer in all subjects. Tv and ventricular volume data were compared among the PD and MSA patients and age-matched controls. We also evaluated the relationship between Tv and age in the 114 all-age controls, controlling for ventricular volume. Men and women were analyzed separately. The male PD and MSA patients had significantly higher Tv values compared to the male controls, with no significant difference in ventricular volume among them. There was no significant difference in Tv between the female patients and controls. In the all-age male controls, there was a significant negative correlation between Tv and age controlling for ventricular volume, and this was not observed in the women. DWI thermometry is a useful and easy method for demonstrating an altered intracranial environment in male patients and healthy controls, but not in females. DWI thermometry can thus be used to help to explore the pathophysiology of Parkinsonian syndromes and to differentiate individuals affected by neurodegenerative disease with autonomic dysfunction from those without it.

  8. The utility of susceptibility-weighted imaging for differentiating Parkinsonism-predominant multiple system atrophy from Parkinson's disease: correlation with 18F-flurodeoxyglucose positron-emission tomography.

    PubMed

    Yoon, Ra Gyoung; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Kim, Jae Seung; Oh, Jungsu; Chung, Sun J; Lee, Chong Sik

    2015-01-01

    Our study was intended to demonstrate the different signal intensity (SI) pattern of the putamen seen on susceptibility-weighted imaging (SWI) between that of Parkinson's disease (PD) and Parkinsonism-predominant multiple system atrophy (MSA-P), and to correlate it with (18)F-flurodeoxyglucose positron-emission tomography ((18)F-FDG PET). Thirty patients with PD and 17 with MSA-P underwent SWI, and (18)F-FDG PET were included. The SI was measured on SWI in the anterior and posterior halves of the putamen using a region-of-interest (ROI) on both sides. The normalized regional glucose metabolism (standardized uptake value ratio, SUVR) was measured on co-registered (18)F-FDG PET images using the ROI obtained with SWI. Analysis included a group-level comparison of the SI values obtained on SWI, and these results were correlated with the SUVR on (18)F-FDG PET. The SIs of the bilateral posterior, dominant-side of the posterior, mean values of the bilateral anterior and posterior halves of the putamen on SWI, differed significantly between the two groups (P < 0.001, respectively). The SUVR of the all locations also differed significantly between PD and MSA-P (P < 0.001, respectively). There was a moderate degree of positive correlation between the SI and the SUVR of the left posterior half, and mean value of the bilateral posterior putamen in MSA-P (r = 0.634, P = 0.006, r = 0.492, P = 0.045). In conclusion, the low SI seen on the posterior putamen may differentiate MSA-P from PD. Furthermore, low SI in the putamen correlated with hypometabolism on (18)F-FDG PET. Therefore, SWI could be a potential complementary diagnostic tool to (18)F-FDG PET for differentiating these conditions.

  9. Using 'swallow-tail' sign and putaminal hypointensity as biomarkers to distinguish multiple system atrophy from idiopathic Parkinson's disease: A susceptibility-weighted imaging study.

    PubMed

    Wang, Na; Yang, HuaGuang; Li, ChengBo; Fan, GuoGuang; Luo, XiaoGuang

    2017-08-01

    To investigate the value of 'swallow-tail' sign and putaminal hypointensity on 3 T susceptibility-weighted imaging (SWI) for distinguishing multiple system atrophy (MSA) from idiopathic Parkinson's disease (IPD). Three groups - 39 MSA patients, 18 IPD patients,and 31 healthy controls (HCs) - were administered a 3 T SWI sequence to evaluate 'swallow-tail' sign and putaminal hypointensity using visual scales from 0 to 2 and 0 to 3 scores, respectively. The diagnostic accuracy of the two signs separately and combined was calculated using a receiver operating characteristic curve, with clinical diagnosis as the gold standard. The scores of 'swallow-tail' sign were lower in IPD than in MSA or in HCs, as well as for putaminal hypointensity in IPD or HCs than in MSA (p < 0.05). The sensitivity and specificity of 'swallow-tail' sign and putaminal hypointensity were 87.9% and 83.3%, and 35.9% and 100%, respectively, in the respective patient groups. The area under the curve of combined signs was increased from 0.85 ('swallow tail') or 0.68 (putaminal hypointensity) to 0.93. The combination of 'swallow-tail' sign and putaminal hypointensity can increase the accuracy of discriminating between MSA and IPD. • Differential diagnosis of MSA and IPD is still challenging in clinical practice. • Absence of 'swallow-tail' sign is a valuable biomarker for IPD on SWI. • Putaminal hypointensity is a valuable biomarker for MSA on SWI. • Combined 'swallow- tail' sign and putaminal hypointensity increase diagnostic accuracy.

  10. Intraventricular cerebrospinal fluid temperature analysis using MR diffusion-weighted imaging thermometry in Parkinson's disease patients, multiple system atrophy patients, and healthy subjects

    PubMed Central

    Sumida, Kaoru; Sato, Noriko; Ota, Miho; Sakai, Koji; Nippashi, Yasumasa; Sone, Daichi; Yokoyama, Kota; Ito, Kimiteru; Maikusa, Norihide; Imabayashi, Etsuko; Matsuda, Hiroshi; Yamada, Kei; Murata, Miho; Kunimatsu, Akira; Ohtomo, Kuni

    2015-01-01

    Purpose We examined the temperature of the intraventricular cerebrospinal fluid (Tv) in patients with Parkinson's disease (PD) and those with multiple system atrophy (MSA) in comparison with healthy subjects, and we examined normal changes in this temperature with aging. Methods Tv was estimated by magnetic resonance (MR) diffusion-weighted imaging (DWI) thermometry in 36 PD patients (19 males, 17 females), 34 MSA patients (17 males, 17 females), 64 age-matched controls (27 men, 37 women), and 114 all-age adult controls (47 men, 67 women; 28–89 years old). The volume of lateral ventricles was also estimated using FreeSurfer in all subjects. Tv and ventricular volume data were compared among the PD and MSA patients and age-matched controls. We also evaluated the relationship between Tv and age in the 114 all-age controls, controlling for ventricular volume. Men and women were analyzed separately. Results The male PD and MSA patients had significantly higher Tv values compared to the male controls, with no significant difference in ventricular volume among them. There was no significant difference in Tv between the female patients and controls. In the all-age male controls, there was a significant negative correlation between Tv and age controlling for ventricular volume, and this was not observed in the women. Conclusion DWI thermometry is a useful and easy method for demonstrating an altered intracranial environment in male patients and healthy controls, but not in females. DWI thermometry can thus be used to help to explore the pathophysiology of Parkinsonian syndromes and to differentiate individuals affected by neurodegenerative disease with autonomic dysfunction from those without it. PMID:26085965

  11. MRI derived brain atrophy in PSP and MSA-P. Determining sample size to detect treatment effects.

    PubMed

    Paviour, Dominic C; Price, Shona L; Lees, Andrew J; Fox, Nick C

    2007-04-01

    Progressive supranuclear palsy (PSP) and multiple system (MSA) atrophy are associated with progressive brain atrophy. Serial MRI can be applied in order to measure this change in brain volume and to calculate atrophy rates. We evaluated MRI derived whole brain and regional atrophy rates as potential markers of progression in PSP and the Parkinsonian variant of multiple system atrophy (MSA-P). 17 patients with PSP, 9 with MSA-P and 18 healthy controls underwent two MRI brain scans. MRI scans were registered, and brain and regional atrophy rates (midbrain, pons, cerebellum, third and lateral ventricles) measured. Sample sizes required to detect the effect of a proposed disease-modifying treatment were estimated. The effect of scan interval on the variance of the atrophy rates and sample size was assessed. Based on the calculated yearly rates of atrophy, for a drug effect equivalent to a 30% reduction in atrophy, fewer PSP subjects are required in each treatment arm when using midbrain rather than whole brain atrophy rates (183 cf. 499). Fewer MSA-P subjects are required, using pontine/cerebellar, rather than whole brain atrophy rates (164/129 cf. 794). A reduction in the variance of measured atrophy rates was observed with a longer scan interval. Regional rather than whole brain atrophy rates calculated from volumetric serial MRI brain scans in PSP and MSA-P provide a more practical and powerful means of monitoring disease progression in clinical trials.

  12. The Bethesda system for reporting thyroid cytopathology in Colombia: Correlation with histopathological diagnoses in oncology and non-oncology institutions

    PubMed Central

    Melo-Uribe, Mario Alexander; Sanabria, Álvaro; Romero-Rojas, Alfredo; Pérez, Gabriel; Vargas, Elga Johanna; Abaúnza, María Claudia; Gutiérrez, Víctor

    2015-01-01

    Aim: To determine the correlation between the results of thyroid fine-needle aspirations interpreted using the Bethesda system and final histopathological reports for patients at an oncology hospital (OH) and non-oncology hospitals (NOHs). Materials and Methods: A retrospective, cross-sectional, descriptive study was performed to compare the cytology and histopathology results for patients with thyroid nodules in three Colombian hospitals. The final correlation of diagnoses between the two methods is reported. In Colombia, the health system provides the existence of general care hospitals and hospitals specializing in care of patients with cancer. Results: A total of 196 reports were reviewed, of which 53% were from OH and 47% were from NOHs. A greater proportion of category V (37.5%) was diagnosed at the OH, whereas NOHs diagnosed a greater proportion of category II (42.3%). The global correlation between diagnoses made using cytology and histopathology was 93.3% for categories V and VI (based on the final malignant diagnosis) and 86.9% for benign category II. Significant differences between institution types were observed when category IV and V and malignant histopathology were compared (56.3% OH vs. 23.5% NOH; P = 0.05 for category IV, 97.4% OH vs. 82.3% NOH; P = 0.03 for category V), while no significant difference between institution types was observed when category II and final benign diagnosis were compared (P = 0.6). Conclusions: The Bethesda system for thyroid cytology correlates adequately with final histopathological diagnosis in Colombia. Significant differences were identified in the diagnostic correlation for malignant lesions between the OH and NOHs in categories IV and V caused by selection bias of the population. PMID:25948937

  13. Spinal muscular atrophy

    PubMed Central

    2011-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40-1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity. Differential diagnosis should be considered with other neuromuscular disorders which are not associated with increased CK manifesting as infantile hypotonia or as limb girdle weakness starting later in life. Considering the high carrier frequency, carrier testing is requested by siblings of patients or of parents of SMA children and are aimed at gaining information that may help with reproductive planning. Individuals at risk should be tested first and, in case of testing positive, the partner should be then analyzed. It is recommended that in case of a request on carrier testing on siblings of an affected SMA infant, a detailed neurological examination should be done and consideration given doing the direct test to exclude SMA. Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%). The role of follow-up coordination has to be managed by an expert in neuromuscular disorders and in SMA who is able to plan a multidisciplinary intervention that includes pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis depends on the phenotypic

  14. Spinal muscular atrophy.

    PubMed

    D'Amico, Adele; Mercuri, Eugenio; Tiziano, Francesco D; Bertini, Enrico

    2011-11-02

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40-1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity. Differential diagnosis should be considered with other neuromuscular disorders which are not associated with increased CK manifesting as infantile hypotonia or as limb girdle weakness starting later in life. Considering the high carrier frequency, carrier testing is requested by siblings of patients or of parents of SMA children and are aimed at gaining information that may help with reproductive planning. Individuals at risk should be tested first and, in case of testing positive, the partner should be then analyzed. It is recommended that in case of a request on carrier testing on siblings of an affected SMA infant, a detailed neurological examination should be done and consideration given doing the direct test to exclude SMA. Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%). The role of follow-up coordination has to be managed by an expert in neuromuscular disorders and in SMA who is able to plan a multidisciplinary intervention that includes pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis depends on the phenotypic

  15. Diagnostic Approach to Childhood-onset Cerebellar Atrophy: A 10-Year Retrospective Study of 300 Patients

    PubMed Central

    Al-Maawali, Almundher; Blaser, Susan; Yoon, Grace

    2013-01-01

    Hereditary ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. Selection of appropriate clinical and genetic tests for patients with cerebellar atrophy poses a diagnostic challenge. Neuroimaging is a crucial initial investigation in the diagnostic evaluation of ataxia in childhood, and the presence of cerebellar atrophy helps guide further investigations. We performed a detailed review of 300 patients with confirmed cerebellar atrophy on magnetic resonance imaging over a 10-year period. A diagnosis was established in 47% of patients: Mitochondrial disorders were most common, followed by the neuronal ceroid lipofuscinoses, ataxia telangectasia, and late GM2-gangliosidosis. We review the common causes of cerebellar atrophy in childhood and propose a diagnostic approach based on correlating specific neuroimaging patterns with clinical and genetic diagnoses. PMID:22764178

  16. Research opportunities in muscle atrophy

    NASA Technical Reports Server (NTRS)

    Herbison, G. J.; Talbot, J. M.

    1984-01-01

    A trophy of skeletal muscle; muscle a trophy associated with manned space flight; the nature, causes, and mechanisms of muscle atrophy associated with space flight, selected physiological factors, biochemical aspects, and countermeasures are addressed.

  17. Spinal muscular atrophies.

    PubMed

    Viollet, Louis; Melki, Judith

    2013-01-01

    Spinal muscular atrophies (SMA) are genetic disorders characterized by degeneration of lower motor neurons. The most frequent form is caused by mutations of the survival motor neuron 1 gene (SMN1). The identification of this gene greatly improved diagnostic testing and family-planning options of SMA families. SMN plays a key role in metabolism of RNA. However, the link between RNA metabolism and motor neuron degeneration remains unknown. A defect in mRNA processing likely generates either a loss of function of some critical RNA or abnormal transcripts with toxic property for motor neurons. Mutations of SMN in various organisms highlighted an essential role of SMN in motor axon and neuromuscular junction development or maintenance. The quality of life of patients has greatly improved over recent decades through the improvement of care and management of patients. In addition, major advances in translational research have been made in the field of SMA. Various therapeutic strategies have been successfully developed aiming at acting on SMN2, a partially functional copy of the SMN1 gene which remains present in patients. Drugs have been identified and some are already at preclinical stages. Identifying molecules involved in the SMA degenerative process should represent additional attractive targets for therapeutics in SMA. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Cellular and molecular mechanisms of muscle atrophy

    PubMed Central

    Bonaldo, Paolo; Sandri, Marco

    2013-01-01

    Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases. PMID:23268536

  19. Angiotensin II: role in skeletal muscle atrophy.

    PubMed

    Cabello-Verrugio, Claudio; Córdova, Gonzalo; Salas, José Diego

    2012-09-01

    Skeletal muscle, the main protein reservoir in the body, is a tissue that exhibits high plasticity when exposed to changes. Muscle proteins can be mobilized into free amino acids when skeletal muscle wasting occurs, a process called skeletal muscle atrophy. This wasting is an important systemic or local manifestation under disuse conditions (e.g., bed rest or immobilization), in starvation, in older adults, and in several diseases. The molecular mechanisms involved in muscle wasting imply the activation of specific signaling pathways which ultimately manage muscle responses to modulate biological events such as increases in protein catabolism, oxidative stress, and cell death by apoptosis. Many factors have been involved in the generation and maintenance of atrophy in skeletal muscle, among them angiotensin II (Ang-II), the main peptide of renin-angiotensin system (RAS). Together with Ang-II, the angiotensin-converting enzyme (ACE) and the Ang-II receptor type 1 (AT-1 receptor) are expressed in skeletal muscle, forming an important local axis that can regulate its function. In many of the conditions that lead to muscle wasting, there is an impairment of RAS in a global or local fashion. At this point, there are several pieces of evidence that suggest the participation of Ang-II, ACE, and AT-1 receptor in the generation of skeletal muscle atrophy. Interestingly, the Ang-II participation in muscle atrophy is strongly ligated to the regulation of hypertrophic activity of factors such as insulin-like growth factor 1 (IGF-1). In this article, we reviewed the current state of Ang-II and RAS function on skeletal muscle wasting and its possible use as a therapeutic target to improve skeletal muscle function under atrophic conditions.

  20. Usefulness of the MrWALLETS Scoring System to Predict First Diagnosed Atrial Fibrillation in Patients With Ischemic Stroke.

    PubMed

    Muscari, Antonio; Bonfiglioli, Andrea; Faccioli, Luca; Ghinelli, Marco; Magalotti, Donatella; Manzetto, Francesco; Pontarin, Anna; Puddu, Giovanni M; Spinardi, Luca; Tubertini, Eleonora; Zoli, Marco

    2017-04-01

    Some cryptogenic strokes are caused by undetected paroxysmal atrial fibrillation (AF) and could benefit from oral anticoagulation. In this study, we searched for echocardiographic parameters associated with first diagnosed AF, to form a scoring system for the identification of patients with AF. We examined 571 patients with ischemic stroke (72.7 ± 13.5 years, 50.6% women), subdivided into 4 groups: documented cause without AF, first diagnosed AF, known paroxysmal AF, and permanent AF. All patients underwent transthoracic echocardiography, brain computed tomography scan, carotid/vertebral ultrasound, and continuous electrocardiographic monitoring. Eight factors independently characterized first diagnosed AF and formed the "MrWALLETS" score: mitral regurgitation, mild-to-moderate (+1), white matter lesions (-1), age ≥75 years (+1), left atrium ≥4 cm (+1), cerebral lesion diameter ≥4 cm (+1), left ventricular end-diastolic volume <65 ml (+1), tricuspid regurgitation ≥moderate (+1), carotid stenosis ≥50% (-1). In the patients with ≥3 points, positive predictive value was 80%, specificity 97.5%, and sensitivity 57.1%. In the patients with ≥2 points sensitivity rose to 85.7%, but positive predictive value was 47.1%. The area under the receiver-operating characteristic curve was 0.89 (95% CI 0.83 to 0.95). There were important differences among AF groups, which therefore could not be merged. In conclusion, 4 echocardiographic parameters, 3 additional instrumental parameters, and age allow the identification of stroke patients with first diagnosed AF with high positive predictive value.

  1. Atrophying tinea versicolor: a clinical and histological study of 12 patients.

    PubMed

    Crowson, A N; Magro, C M

    2003-12-01

    We describe 12 patients with an atrophying dermatitis in whom the biopsy findings were compatible with tinea versicolor. We encountered 12 skin biopsies from 12 patients in whom a clinically atrophying dermatosis was associated with light microscopic (LM) evidence of atrophy and epidermal colonization by Pityrosporum sp. Formalin-fixed, paraffin-embedded tissue sections were cut at 5 microns and stained with H&E, alcian blue-PAS and PAS-diastase preparations. Five men and seven women aged 17-73 years in whom lesions characterized as atrophic plaques, patches or macules prompted clinical differential diagnoses including parapsoriasis or mycosis fungoides (MF), anetoderma, lupus erythematosus, and steroid atrophy. A LM examination showed epidermal colonization with pityrosporum hyphae and spores accompanied by variable epidermal and dermal atrophy characterized by rete-ridge effacement, subepidermal fibroplasia, pigment incontinence and elastolysis. Atrophying cutaneous lesions comprise part of the clinical spectrum of tinea versicolor for which we propose the term 'atrophying tinea versicolor'. The pathogenetic basis is unclear but could be the sequela of delayed type hypersensitivity and the release by T-helper lymphocytes of leukotrienes which perturb collagen metabolism and/or keratinocyte growth. Lesions may be mistaken clinically for MF or other atrophying dermatoses.

  2. Autosomal dominant congenital spinal muscular atrophy: a true form of spinal muscular atrophy caused by early loss of anterior horn cells.

    PubMed

    Oates, Emily C; Reddel, Stephen; Rodriguez, Michael L; Gandolfo, Luke C; Bahlo, Melanie; Hawke, Simon H; Lamandé, Shireen R; Clarke, Nigel F; North, Kathryn N

    2012-06-01

    Autosomal dominant congenital spinal muscular atrophy is characterized by predominantly lower limb weakness and wasting, and congenital or early-onset contractures of the hip, knee and ankle. Mutations in TRPV4, encoding a cation channel, have recently been identified in one large dominant congenital spinal muscular atrophy kindred, but the genetic basis of dominant congenital spinal muscular atrophy in many families remains unknown. It has been hypothesized that differences in the timing and site of anterior horn cell loss in the central nervous system account for the variations in clinical phenotype between different forms of spinal muscular atrophy, but there has been a lack of neuropathological data to support this concept in dominant congenital spinal muscular atrophy. We report clinical, electrophysiology, muscle magnetic resonance imaging and histopathology findings in a four generation family with typical dominant congenital spinal muscular atrophy features, without mutations in TRPV4, and in whom linkage to other known dominant neuropathy and spinal muscular atrophy genes has been excluded. The autopsy findings in the proband, who died at 14 months of age from an unrelated illness, provided a rare opportunity to study the neuropathological basis of dominant congenital spinal muscular atrophy. There was a reduction in anterior horn cell number in the lumbar and, to a lesser degree, the cervical spinal cord, and atrophy of the ventral nerve roots at these levels, in the absence of additional peripheral nerve pathology or abnormalities elsewhere along the neuraxis. Despite the young age of the child at the time of autopsy, there was no pathological evidence of ongoing loss or degeneration of anterior horn cells suggesting that anterior horn cell loss in dominant congenital spinal muscular atrophy occurs in early life, and is largely complete by the end of infancy. These findings confirm that dominant congenital spinal muscular atrophy is a true form of spinal

  3. Space travel directly induces skeletal muscle atrophy

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  4. Space travel directly induces skeletal muscle atrophy.

    PubMed

    Vandenburgh, H; Chromiak, J; Shansky, J; Del Tatto, M; Lemaire, J

    1999-06-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  5. Space travel directly induces skeletal muscle atrophy

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  6. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy

    PubMed Central

    Kaski, Diego; Yong, Keir X. X.; Paterson, Ross W.; Slattery, Catherine F.; Ryan, Natalie S.; Schott, Jonathan M.; Crutch, Sebastian J.

    2015-01-01

    The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal ‘visual dementia’ and most common atypical Alzheimer’s disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients’ (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer’s disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer’s disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer’s disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with ‘sticky fixation’. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer’s disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large

  7. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy.

    PubMed

    Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J

    2015-07-01

    The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal 'visual dementia' and most common atypical Alzheimer's disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients' (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer's disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer's disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer's disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with 'sticky fixation'. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer's disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions

  8. (131)I-MIBG myocardial scintigraphy for differentiation of Parkinson's disease from multiple system atrophy or essential tremor in Chinese population.

    PubMed

    Yang, Tuanfeng; Wang, Li; Li, Yuan; Cheng, Min; Jiao, Jinsong; Wang, Qian; Guo, Huailian

    2017-02-15

    Clinical distinction of Parkinson's disease (PD) from multiple system atrophy (MSA) or essential tremor (ET) is sometimes difficult. The purpose of this study was to assess changes in cardiac sympathetic nerve function in PD, MSA, and ET by (131)I-MIBG myocardial scintigraphy METHODS: Patients with PD (25), MSA (18), or ET (11) and 10 healthy controls (HC) were enrolled. (131)I-MIBG myocardial scintigraphy was performed for each subject, and heart/mediastinum (H/M) ratios were calculated at two sample times (15min and 4h after the injection of (131)I-MIBG), representing the (131)I-MIBG myocardial uptake ratios. The washout ratio (WOR) of MIBG which indicates the activity tone of the presynaptic sympathetic nerves was calculated for each subject. The H/M ratios at the two sample times (15min and 4h) were 1.65±0.36 and 1.50±0.43 in the PD group, 1.97±0.36 and 2.08±0.57 in the MSA group, 2.34±0.34 and 2.46±0.51 in the ET group, and 2.41±0.26 and 2.66±0.47 in the HC group. The H/M ratios at the two sample times were lower in the PD group than in the MSA, ET, or HC groups, with statistical significance (all P<0.05). The H/M ratios at the two sample times were significantly lower in the MSA group than in the HC group (all P<0.05). There was no significant difference in H/M ratios at either sample time between the ET and HC group (all P>0.05). The washout ratios (WORs) of MIBG were significantly increased in PD group compared with those in MSA, ET and HC groups. In subgroup analysis, The H/M ratios at the two sample times were decreased in early PD group compared with those in early MSA and early ET groups, with statistical significance (all P<0.05). Cardiac sympathetic dysfunction can occur in both PD and MSA patients, especially in PD patients, whereas it remains normal in ET patients. (131)I-MIBG myocardial scintigraphy can help distinguish patients with PD from those with MSA or ET with good sensitivity and specificity. Copyright © 2016 Elsevier B.V. All

  9. Comparison Study of Polysomnographic Features in Multiple System Atrophy-cerebellar Types Combined with and without Rapid Eye Movement Sleep Behavior Disorder

    PubMed Central

    Ding, Yan; Hu, Yue-Qing; Zhan, Shu-Qin; Li, Cun-Jiang; Wang, Hong-Xing; Wang, Yu-Ping

    2016-01-01

    Background: The brain stem is found to be impaired in multiple system atrophy-cerebellar types (MSA-C). Rapid eye movement (REM) sleep behavior disorder (RBD) is reported as a marker of progressive brain stem dysfunction. Few systematic studies about the sleep disturbances in MSA-C patients combined with or without RBD were reported. This study aimed to explore the polysomnographic (PSG) features of sleep disturbances between MSA-C patients with and without RBD. Methods: Totally, 46 MSA-C patients (23 with RBD, and 23 without RBD) were enrolled in this study. All patients underwent a structured interview for their demographic data, history of sleep pattern, and movement disorders; and then, overnight video-PSG was performed in each patient. All the records were evaluated by specialists at the Sleep Medicine Clinic for RBD and the Movement Disorder Clinic for MSA-C. The Student's t-test, Mann-Whitney U-test for continuous variables, and the Chi-square test for categorical variables were used in this study. Results: MSA-C patients with RBD had younger visiting age (52.6 ± 7.4 vs. 56.7 ± 6.0 years, P = 0.046) and shorter duration of the disease (12.0 [12.0, 24.0] vs. 24.0 [14.0, 36.0] months, P = 0.009) than MSA-C patients without RBD. MSA-C with RBD had shorter REM sleep latency (111.7 ± 48.2 vs. 157.0 ± 68.8 min, P = 0.042), higher percentage of REM sleep (14.9% ±4.0% vs. 10.0% ± 3.2%, P = 0.019), and lower Stage I (9.5% ±7.2% vs. 15.9% ±8.0%, P = 0.027) than MSA-C without RBD. Moreover, MSA-C patients with RBD had more decreased sleep efficiency (52.4% ±12.6% vs. 65.8% ±15.9%, P = 0.029) than that without RBD. Conclusions: In addition to the RBD, MSA-C patients with RBD had other more severe sleep disturbances than those without RBD. The sleep disorders of MSA patients might be associated with the progress of the disease. PMID:27625088

  10. Changes in the miRNA-mRNA Regulatory Network Precede Motor Symptoms in a Mouse Model of Multiple System Atrophy: Clinical Implications

    PubMed Central

    Refolo, Violetta; Venezia, Serena; Sturm, Edith; Piatti, Paolo; Hechenberger, Clara; Hackl, Hubert; Kessler, Roman; Willi, Michaela; Gstir, Ronald; Krogsdam, Anne; Lusser, Alexandra; Poewe, Werner; Wenning, Gregor K.; Hüttenhofer, Alexander; Stefanova, Nadia

    2016-01-01

    Multiple system atrophy (MSA) is a fatal rapidly progressive α-synucleinopathy, characterized by α-synuclein accumulation in oligodendrocytes. It is accepted that the pathological α-synuclein accumulation in the brain of MSA patients plays a leading role in the disease process, but little is known about the events in the early stages of the disease. In this study we aimed to define potential roles of the miRNA-mRNA regulatory network in the early pre-motor stages of the disease, i.e., downstream of α-synuclein accumulation in oligodendroglia, as assessed in a transgenic mouse model of MSA. We investigated the expression patterns of miRNAs and their mRNA targets in substantia nigra (SN) and striatum, two brain regions that undergo neurodegeneration at a later stage in the MSA model, by microarray and RNA-seq analysis, respectively. Analysis was performed at a time point when α-synuclein accumulation was already present in oligodendrocytes at neuropathological examination, but no neuronal loss nor deficits of motor function had yet occurred. Our data provide a first evidence for the leading role of gene dysregulation associated with deficits in immune and inflammatory responses in the very early, non-symptomatic disease stages of MSA. While dysfunctional homeostasis and oxidative stress were prominent in SN in the early stages of MSA, in striatum differential gene expression in the non-symptomatic phase was linked to oligodendroglial dysfunction, disturbed protein handling, lipid metabolism, transmembrane transport and altered cell death control, respectively. A large number of putative miRNA-mRNAs interaction partners were identified in relation to the control of these processes in the MSA model. Our results support the role of early changes in the miRNA-mRNA regulatory network in the pathogenesis of MSA preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards

  11. Lessons Learned from using a Livingstone Model to Diagnose a Main Propulsion System

    NASA Technical Reports Server (NTRS)

    Sweet, Adam; Bajwa, Anupa

    2003-01-01

    NASA researchers have demonstrated that qualitative, model-based reasoning can be used for fault detection in a Main Propulsion System (MPS), a complex, continuous system. At the heart of this diagnostic system is Livingstone, a discrete, propositional logic-based inference engine. Livingstone comprises a language for specifying a discrete model of the system and a set of algorithms that use the model to track the system's state. Livingstone uses the model to test assumptions about the state of a component - observations from the system are compared with values predicted by the model. The intent of this paper is to summarize some advantages of Livingstone seen through our modeling experience: for instance, flexibility in modeling, speed and maturity. We also describe some shortcomings we perceived in the implementation of Livingstone, such as modeling continuous dynamics and handling of transients. We list some upcoming enhancements to the next version of Livingstone that may resolve some of the current limitations.

  12. Correlation of hippocampal atrophy with hyperhomocysteinemia in hemodialysis patients: An exploratory pilot study.

    PubMed

    Maesato, Kyoko; Ohtake, Takayasu; Mochida, Yasuhiro; Ishioka, Kunihiro; Oka, Machiko; Moriya, Hidekazu; Hidaka, Sumi; Kobayashi, Shuzo

    2017-01-01

    Cognitive impairment is one of the important critical issues in hemodialysis (HD) patients. However, the associating factors of brain atrophy in HD patients have not been fully elucidated. Brain magnetic resonance imaging (MRI) was performed in 34 of total 72 HD outpatients in our dialysis center. These MRI images were analyzed by an application software; Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD). VSRAD quantitatively calculates the extent of brain atrophy (percent of volume reduction) comparing with a MRI imaging database of 80 age-matched healthy controls. The extent of both hippocampal and whole-brain atrophy was evaluated with possible contributing factors. In all patients, the mean extent of hippocampal atrophy was 27.3%, and the mean extent of whole-brain atrophy was 11.2%. The extent of hippocampal atrophy was significantly correlated with low body mass index (BMI), total serum homocysteine (tHcy) levels, and brachial-ankle pulse wave velocity (baPWV). The extent of whole-brain atrophy showed significant correlations with age, hypoalbuminemia, and baPWV. Based on the multiple regression analysis, tHcy was an independent determinant of hippocampal atrophy (β = 0.460, R2 = 0.189, P<0.01); while age was an independent determinant of whole-brain atrophy (β = 0.594, R2 = 0.333, P<0.01). In this exploratory pilot study, hippocampal atrophy was significantly correlated with hyperhomocysteinemia in HD patients.

  13. An artificial neural network system for diagnosing gas turbine engine fuel faults

    SciTech Connect

    Illi, O.J. Jr.; Greitzer, F.L.; Kangas, L.J.; Reeve, T.

    1994-04-01

    The US Army Ordnance Center & School and Pacific Northwest Laboratories are developing a turbine engine diagnostic system for the M1A1 Abrams tank. This system employs Artificial Neural Network (AN) technology to perform diagnosis and prognosis of the tank`s AGT-1500 gas turbine engine. This paper describes the design and prototype development of the ANN component of the diagnostic system, which we refer to as ``TEDANN`` for Turbine Engine Diagnostic Artificial Neural Networks.

  14. Storage and retrieval of SNOP-coded pathologic diagnoses using offsite computing and optical character recognizing systems.

    PubMed

    Cechner, R L; Carter, J R

    1976-05-01

    A computerized cross-reference system for retrieving autopsy and surgical pathology cases on the basis of case number or diagnosis has been implemented. The system achieves economy and flexibility by using offsite computer service bureaus for job production, eliminating the need for expensive onsite equipment. Coded diagnoses may be typed using the OCR (Optical Character Recognition) font simultaneously with or separately from the clinical documentation. The flexibility of new OCR equipment permits production of machine-readable code sheets with an ordinary pencil and completely eliminates the need for typing. The system produces year-to-date books that list all diagnoses, on an accumulating basis, in alphabetic order by SNOP* topology, morphology, etiology and function, and will be compatible with SNOMed. Because all data are stored on magnetic tape, they may be manipulated and retrieved as desired through user programming. The initial setup cost was dollar 1,000 for programming and testing, and production runs and all report printing cost about dollar 1,000 per year (autopsies and surgical pathology cases), which is about 1.1 cents per diagnosis.

  15. Cardiac transplant in young female patient diagnosed with diffuse systemic sclerosis.

    PubMed

    Bennasar, Guillermo; Carlevaris, Leandro; Secco, Anastasia; Romanini, Felix; Mamani, Marta

    2016-01-01

    Systemic sclerosis (SS) in a multifactorial and systemic, chronic, autoimmune disease that affects the connective tissue. We present this clinical case given the low prevalence of diffuse SS with early and progressive cardiac compromise in a young patient, and treatment with cardiac transplantation.

  16. Diagnosing Students' Mental Models via the Web-Based Mental Models Diagnosis System

    ERIC Educational Resources Information Center

    Wang, Tzu-Hua; Chiu, Mei-Hung; Lin, Jing-Wen; Chou, Chin-Cheng

    2013-01-01

    Mental models play an important role in science education research. To extend the effectiveness of conceptual change research and to improve mental model identi?cation and diagnosis, the authors developed and tested the Web-Based Mental Models Diagnosis (WMMD) system. In this article, they describe their WMMD system, which goes beyond the…

  17. An integrated decision support system for diagnosing and managing patients with community-acquired pneumonia.

    PubMed Central

    Aronsky, D.; Haug, P. J.

    1999-01-01

    Decision support systems that integrate guidelines have become popular applications to reduce variation and deliver cost-effective care. However, adverse characteristics of decision support systems, such as additional and time-consuming data entry or manually identifying eligible patients, result in a "behavioral bottleneck" that prevents decision support systems to become part of the clinical routine. This paper describes the design and the implementation of an integrated decision support system that explores a novel approach for bypassing the behavioral bottleneck. The real-time decision support system does not require health care providers to enter additional data and consists of a diagnostic and a management component. Images Fig. 1 Fig. 2 Fig. 3 PMID:10566348

  18. Artificial intelligence techniques applied to the development of a decision–support system for diagnosing celiac disease

    PubMed Central

    Tenório, Josceli Maria; Hummel, Anderson Diniz; Cohrs, Frederico Molina; Sdepanian, Vera Lucia; Pisa, Ivan Torres; de Fátima Marin, Heimar

    2013-01-01

    Background Celiac disease (CD) is a difficult-to-diagnose condition because of its multiple clinical presentations and symptoms shared with other diseases. Gold-standard diagnostic confirmation of suspected CD is achieved by biopsying the small intestine. Objective To develop a clinical decision–support system (CDSS) integrated with an automated classifier to recognize CD cases, by selecting from experimental models developed using intelligence artificial techniques. Methods A web-based system was designed for constructing a retrospective database that included 178 clinical cases for training. Tests were run on 270 automated classifiers available in Weka 3.6.1 using five artificial intelligence techniques, namely decision trees, Bayesian inference, k-nearest neighbor algorithm, support vector machines and artificial neural networks. The parameters evaluated were accuracy, sensitivity, specificity and area under the ROC curve (AUC). AUC was used as a criterion for selecting the CDSS algorithm. A testing database was constructed including 38 clinical CD cases for CDSS evaluation. The diagnoses suggested by CDSS were compared with those made by physicians during patient consultations. Results The most accurate method during the training phase was the averaged one-dependence estimator (AODE) algorithm (a Bayesian classifier), which showed accuracy 80.0%, sensitivity 0.78, specificity 0.80 and AUC 0.84. This classifier was integrated into the web-based decision–support system. The gold-standard validation of CDSS achieved accuracy of 84.2% and k = 0.68 (p < 0.0001) with good agreement. The same accuracy was achieved in the comparison between the physician’s diagnostic impression and the gold standard k = 0. 64 (p < 0.0001). There was moderate agreement between the physician’s diagnostic impression and CDSS k = 0.46 (p = 0.0008). Conclusions The study results suggest that CDSS could be used to help in diagnosing CD, since the algorithm tested achieved excellent

  19. Artificial intelligence techniques applied to the development of a decision-support system for diagnosing celiac disease.

    PubMed

    Tenório, Josceli Maria; Hummel, Anderson Diniz; Cohrs, Frederico Molina; Sdepanian, Vera Lucia; Pisa, Ivan Torres; de Fátima Marin, Heimar

    2011-11-01

    Celiac disease (CD) is a difficult-to-diagnose condition because of its multiple clinical presentations and symptoms shared with other diseases. Gold-standard diagnostic confirmation of suspected CD is achieved by biopsying the small intestine. To develop a clinical decision-support system (CDSS) integrated with an automated classifier to recognize CD cases, by selecting from experimental models developed using intelligence artificial techniques. A web-based system was designed for constructing a retrospective database that included 178 clinical cases for training. Tests were run on 270 automated classifiers available in Weka 3.6.1 using five artificial intelligence techniques, namely decision trees, Bayesian inference, k-nearest neighbor algorithm, support vector machines and artificial neural networks. The parameters evaluated were accuracy, sensitivity, specificity and area under the ROC curve (AUC). AUC was used as a criterion for selecting the CDSS algorithm. A testing database was constructed including 38 clinical CD cases for CDSS evaluation. The diagnoses suggested by CDSS were compared with those made by physicians during patient consultations. The most accurate method during the training phase was the averaged one-dependence estimator (AODE) algorithm (a Bayesian classifier), which showed accuracy 80.0%, sensitivity 0.78, specificity 0.80 and AUC 0.84. This classifier was integrated into the web-based decision-support system. The gold-standard validation of CDSS achieved accuracy of 84.2% and k=0.68 (p<0.0001) with good agreement. The same accuracy was achieved in the comparison between the physician's diagnostic impression and the gold standard k=0. 64 (p<0.0001). There was moderate agreement between the physician's diagnostic impression and CDSS k=0.46 (p=0.0008). The study results suggest that CDSS could be used to help in diagnosing CD, since the algorithm tested achieved excellent accuracy in differentiating possible positive from negative CD

  20. Idiopathic atrophie blanche.

    PubMed

    Amato, Lauretta; Chiarini, Caterina; Berti, Samantha; Massi, Daniela; Fabbri, Paolo

    2006-01-01

    clinical, serologic, histopathologic, and immunopathologic findings, a diagnosis of idiopathic atrophie blanche was made. The patient was treated with dapsone (50 mg p.o. q.d.) and pentoxifylline (400 mg p.o. t.i.d.) with pain relief and complete resolution of the ulcerations after 6 weeks of therapy.

  1. The accuracy of Internet search engines to predict diagnoses from symptoms can be assessed with a validated scoring system.

    PubMed

    Shenker, Bennett S

    2014-02-01

    To validate a scoring system that evaluates the ability of Internet search engines to correctly predict diagnoses when symptoms are used as search terms. We developed a five point scoring system to evaluate the diagnostic accuracy of Internet search engines. We identified twenty diagnoses common to a primary care setting to validate the scoring system. One investigator entered the symptoms for each diagnosis into three Internet search engines (Google, Bing, and Ask) and saved the first five webpages from each search. Other investigators reviewed the webpages and assigned a diagnostic accuracy score. They rescored a random sample of webpages two weeks later. To validate the five point scoring system, we calculated convergent validity and test-retest reliability using Kendall's W and Spearman's rho, respectively. We used the Kruskal-Wallis test to look for differences in accuracy scores for the three Internet search engines. A total of 600 webpages were reviewed. Kendall's W for the raters was 0.71 (p<0.0001). Spearman's rho for test-retest reliability was 0.72 (p<0.0001). There was no difference in scores based on Internet search engine. We found a significant difference in scores based on the webpage's order on the Internet search engine webpage (p=0.007). Pairwise comparisons revealed higher scores in the first webpages vs. the fourth (corr p=0.009) and fifth (corr p=0.017). However, this significance was lost when creating composite scores. The five point scoring system to assess diagnostic accuracy of Internet search engines is a valid and reliable instrument. The scoring system may be used in future Internet research. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Simulation modelling as a tool to diagnose the complex networks of security systems

    NASA Astrophysics Data System (ADS)

    Iskhakov, S. Y.; Shelupanov, A. A.; Meshcheryakov, R. V.

    2017-01-01

    In the article, the questions of modelling of complex security system networks are considered. The simulation model of operation of similar complexes and approbation of the offered approach to identification of the incidents are presented. The approach is based on detection of uncharacteristic alterations of the network operation mode. The results of the experiment allow one to draw a conclusion on possibility of the offered model application to analyse the current status of heterogeneous security systems. Also, it is confirmed that the application of short-term forecasting methods for the analysis of monitoring system data allows one to automate the process of formation the criteria to reveal the incidents.

  3. A method for diagnosing time dependent faults using model-based reasoning systems

    NASA Technical Reports Server (NTRS)

    Goodrich, Charles H.

    1995-01-01

    This paper explores techniques to apply model-based reasoning to equipment and systems which exhibit dynamic behavior (that which changes as a function of time). The model-based system of interest is KATE-C (Knowledge based Autonomous Test Engineer) which is a C++ based system designed to perform monitoring and diagnosis of Space Shuttle electro-mechanical systems. Methods of model-based monitoring and diagnosis are well known and have been thoroughly explored by others. A short example is given which illustrates the principle of model-based reasoning and reveals some limitations of static, non-time-dependent simulation. This example is then extended to demonstrate representation of time-dependent behavior and testing of fault hypotheses in that environment.

  4. [The logic of diagnoses used in expert systems. II. Applications in virology].

    PubMed

    Cristea, A; Zaharia, C N

    1988-01-01

    Inference capacity of different clinical or paraclinical examinations are analyzed, whose results allow to establish the definitive diagnosis through gradual integrations. The knowledge of the inference capacity is very useful for the expert systems applied in virology.

  5. The Meaningfulness of Consensus and Context in Diagnosing Evolvable Production Systems

    NASA Astrophysics Data System (ADS)

    Ribeiro, Luis; Barata, José; Ferreira, João

    An Evolvable Production System (EPS) is a complex and lively entity composed of intelligent modules that interact, through bio-inspired mechanisms, to ensure high system availability and seamless reconfiguration. The diagnosis of such dynamic systems, characterized by constant change, presents new diagnostic challenges and opportunities that can hardly be tackled by traditional approaches. On the one hand, given the decoupled nature of the system, fault interaction and propagation are harder to detect and contain, as is the development of a global diagnostic model, on the other hand local intelligence and careful characterization of the interactions, between the modules, can be explored to emerge the diagnostic functionalities. The impact of simple consensus mechanisms (majority voting) and fault context analysis (module and its current interactions states) is assessed in a multiagent-oriented application in the assembly domain to understand the validity and contribution of this approach in emerging useful self-diagnostic properties in EPS.

  6. Sensor configuration and test for fault diagnoses of subway braking system based on signed digraph method

    NASA Astrophysics Data System (ADS)

    Zuo, Jianyong; Chen, Zhongkai

    2014-05-01

    Fault diagnosis of various systems on rolling stock has drawn the attention of many researchers. However, obtaining an optimized sensor set of these systems, which is a prerequisite for fault diagnosis, remains a major challenge. Available literature suggests that the configuration of sensors in these systems is presently dependent on the knowledge and engineering experiences of designers, which may lead to insufficient or redundant development of various sensors. In this paper, the optimization of sensor sets is addressed by using the signed digraph (SDG) method. The method is modified for use in braking systems by the introduction of an effect-function method to replace the traditional quantitative methods. Two criteria are adopted to evaluate the capability of the sensor sets, namely, observability and resolution. The sensors configuration method of braking system is proposed. It consists of generating bipartite graphs from SDG models and then solving the set cover problem using a greedy algorithm. To demonstrate the improvement, the sensor configuration of the HP2008 braking system is investigated and fault diagnosis on a test bench is performed. The test results show that SDG algorithm can improve single-fault resolution from 6 faults to 10 faults, and with additional four brake cylinder pressure (BCP) sensors it can cover up to 67 double faults which were not considered by traditional fault diagnosis system. SDG methods are suitable for reducing redundant sensors and that the sensor sets thereby obtained are capable of detecting typical faults, such as the failure of a release valve. This study investigates the formal extension of the SDG method to the sensor configuration of braking system, as well as the adaptation supported by the effect-function method.

  7. Postradiation atrophy of mature bone

    SciTech Connect

    Ergun, H.; Howland, W.J.

    1980-01-01

    The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

  8. [Atrophy of the bone marrow].

    PubMed

    Dziecioł, J; Kemona, A; Sulik, M; Sulkowski, S; Brykalska, A; Sobaniec-Lotowska, M; Ostapiuk, H

    1990-01-01

    The authors made a quantitative analysis of the active hematopoietic tissue of the bone marrow with particular consideration of its atrophy in the course of various diseases. The material consisted of 407 non-selected autopsy cases. For a morphometric analysis the bone marrow was sampled from the sternum, ala ossis illi and spine. In the quantitative analysis of the active hematopoietic tissue we took into account age groups as quantitative changes appear with age. Atrophy of the bone marrow was in 19.4% of the studied cases. The presence of bone marrow atrophy was found in the course of various diseases, most frequently neoplastic, particularly in patients aged from 50 to 59 years.

  9. Image Analysis of Chlorophyll Fluorescence Transients for Diagnosing the Photosynthetic System of Attached Leaves

    PubMed Central

    Omasa, Kenji; Shimazaki, Ken-Ichiro; Aiga, Ichiro; Larcher, Walter; Onoe, Morio

    1987-01-01

    A new image instrumentation system for quantitative analysis of the rapid change in intensity of chlorophyll fluorescence during dark-light transition (CFI, chlorophyll fluorescence induction), which is a sensitive indicator of the various reactions of photosynthesis, was developed and its performance was evaluated. This system made it possible to resolve CFI at any small leaf area (about 1 square millimeter) of a whole leaf when the plant was illuminated by blue-green light at more than 50 micromoles photons per square meter per second. In order to test the usefulness of this system, we applied it to analyze the effect of SO2 on photosynthetic apparatus in attached sunflower leaves. Dynamic CFI imaging over the whole single leaf, where there was no visible injury, indicated not only the local changes in photosynthetic activity but also the site of inhibition in photosynthetic electron transport system in chloroplasts. The new instrumentation system will be useful for the analytical diagnosis of various stress-actions on plants in situ. Images Fig. 1 Fig. 5 Fig. 6 PMID:16665515

  10. A Respiratory Movement Monitoring System Using Fiber-Grating Vision Sensor for Diagnosing Sleep Apnea Syndrome

    NASA Astrophysics Data System (ADS)

    Takemura, Yasuhiro; Sato, Jun-Ya; Nakajima, Masato

    2005-01-01

    A non-restrictive and non-contact respiratory movement monitoring system that finds the boundary between chest and abdomen automatically and detects the vertical movement of each part of the body separately is proposed. The system uses a fiber-grating vision sensor technique and the boundary position detection is carried out by calculating the centers of gravity of upward moving and downward moving sampling points, respectively. In the experiment to evaluate the ability to detect the respiratory movement signals of each part and to discriminate between obstructive and central apneas, detected signals of the two parts and their total clearly showed the peculiarities of obstructive and central apnea. The cross talk between the two categories classified automatically according to several rules that reflect the peculiarities was ≤ 15%. This result is sufficient for discriminating central sleep apnea syndrome from obstructive sleep apnea syndrome and indicates that the system is promising as screening equipment. Society of Japan

  11. Optic atrophy and glaucomatous cupping.

    PubMed

    Radius, R L; Maumenee, A E

    1978-02-01

    We reviewed 170 eyes of 112 patients with optic atrophy from various causes. Special attention was directed towards measured cup:disk ratios as well as presence of glaucomatous-like cupping of the optic nerve head. We observed a small but significant increase in nerve head cupping in eyes with optic atrophy when compared to contralateral eyes, as well as to eyes of 50 diabetic patients. No characteristic glaucomatous disk changes were documented. We evaluated these findings with respect to possible causes of glaucomatous disk and field changes.

  12. [Development and application of an immunoenzyme test system for diagnosing Ebola fever].

    PubMed

    Merzlikin, N V; Chepurnov, A A; Istomina, N N; Ofitserov, V I; Vorob'eva, M S

    1995-01-01

    Enzyme immunoassay (EIA) test systems for the detection of antigens of and antibodies to Ebola virus were developed and tried. The test system for the detection of Ebola virus antigens based on direct solid-phase EIA detects viral antigens in culture fluid of infected Vero cells, in the blood sera, and in homogenates of infected tissues. Use of this test system allows detection of at least 10 ng of viral proteins or 5.0 x 10(3) to 1.0 x 10(4) PFU/ml in infectious material. The test system is prepared on the basis of protein A - horseradish peroxidase conjugate. It is universal for the testing of animal and human sera and is characterized by high resolution and reproducibility of results. It allows detection of antibodies to Ebola virus starting from days 8-9 of infection. A higher sensitivity of direct solid-phase EIA in comparison with complement fixation or indirect immunofluorescence tests is demonstrated.

  13. Using an Educational Electronic Documentation System to Help Nursing Students Accurately Identify Nursing Diagnoses

    ERIC Educational Resources Information Center

    Pobocik, Tamara J.

    2013-01-01

    The use of technology and electronic medical records in healthcare has exponentially increased. This quantitative research project used a pretest/posttest design, and reviewed how an educational electronic documentation system helped nursing students to identify the accurate related to statement of the nursing diagnosis for the patient in the case…

  14. Strategies to diagnose and control microbial souring in natural gas storage reservoirs and produced water systems

    SciTech Connect

    Morris, E.A.; Derr, R.M.; Pope, D.H.

    1995-12-31

    Hydrogen sulfide production (souring) in natural gas storage reservoirs and produced water systems is a safety and environmental problem that can lead to operational shutdown when local hydrogen sulfide standards are exceeded. Systems affected by microbial souring have historically been treated using biocides that target the general microbial community. However, requirements for more environmentally friendly solutions have led to treatment strategies in which sulfide production can be controlled with minimal impact to the system and environment. Some of these strategies are based on microbial and/or nutritional augmentation of the sour environment. Through research sponsored by the Gas Research Institute (GRI) in Chicago, Illinois, methods have been developed for early detection of microbial souring in natural gas storage reservoirs, and a variety of mitigation strategies have been evaluated. The effectiveness of traditional biocide treatment in gas storage reservoirs was shown to depend heavily on the methods by which the chemical is applied. An innovative strategy using nitrate was tested and proved ideal for produced water and wastewater systems. Another strategy using elemental iodine was effective for sulfide control in evaporation ponds and is currently being tested in microbially sour natural gas storage wells.

  15. The Accuracy of Expert-System Diagnoses of Mathematical Problem Solutions.

    ERIC Educational Resources Information Center

    Bennett, Randy Elliot; Sebrechts, Marc M.

    1996-01-01

    Four human judges agreed highly among themselves about the presence of errors committed by 60 adults solving algebra word problems, but were in less agreement about categorizing faults. An expert system agreed with judges about correctness of answers, but was in even less agreement about categorizing the faults. (SLD)

  16. Using an Educational Electronic Documentation System to Help Nursing Students Accurately Identify Nursing Diagnoses

    ERIC Educational Resources Information Center

    Pobocik, Tamara J.

    2013-01-01

    The use of technology and electronic medical records in healthcare has exponentially increased. This quantitative research project used a pretest/posttest design, and reviewed how an educational electronic documentation system helped nursing students to identify the accurate related to statement of the nursing diagnosis for the patient in the case…

  17. Comparative analysis of classifiers for developing an adaptive computer-assisted EEG analysis system for diagnosing epilepsy.

    PubMed

    Ahmad, Malik Anas; Ayaz, Yasar; Jamil, Mohsin; Omer Gillani, Syed; Rasheed, Muhammad Babar; Imran, Muhammad; Khan, Nadeem Ahmed; Majeed, Waqas; Javaid, Nadeem

    2015-01-01

    Computer-assisted analysis of electroencephalogram (EEG) has a tremendous potential to assist clinicians during the diagnosis of epilepsy. These systems are trained to classify the EEG based on the ground truth provided by the neurologists. So, there should be a mechanism in these systems, using which a system's incorrect markings can be mentioned and the system should improve its classification by learning from them. We have developed a simple mechanism for neurologists to improve classification rate while encountering any false classification. This system is based on taking discrete wavelet transform (DWT) of the signals epochs which are then reduced using principal component analysis, and then they are fed into a classifier. After discussing our approach, we have shown the classification performance of three types of classifiers: support vector machine (SVM), quadratic discriminant analysis, and artificial neural network. We found SVM to be the best working classifier. Our work exhibits the importance and viability of a self-improving and user adapting computer-assisted EEG analysis system for diagnosing epilepsy which processes each channel exclusive to each other, along with the performance comparison of different machine learning techniques in the suggested system.

  18. Independent cognitive effects of atrophy and diffuse subcortical and thalamico-cortical cerebrovascular disease in dementia.

    PubMed

    Swartz, Richard H; Stuss, Donald T; Gao, Fuqiang; Black, Sandra E

    2008-03-01

    Brain atrophy, cortical infarction, and subcortical ischemic vasculopathy have all been associated with cognitive dysfunction. The interrelationships between these pathologies and their independent contributions to cognitive function remain unclear. Despite the high frequency of Alzheimer disease (AD) in those with clinically diagnosed vascular dementia, and the frequent findings of vascular disease in those with clinically diagnosed AD, many studies of brain-behavior relationships in dementia consider these populations separately. The present study sought to identify the correlates of independent domains of cognitive impairment in an unselected sample across a large range of severity and overlap of AD and VaD. Two hundred five individuals from the Sunnybrook Dementia Study recruited from a university Memory clinic had detailed neuropsychological testing and MRI quantification using a multi-step postprocessing algorithm. A factor analysis of the cognitive protocol yielded a 3-factor solution, provisionally labeled: (1) short-term memory and language, (2) attention and working memory, and (3) mental flexibility. A factor analysis of brain measures identified 3 independent factors with measures of (1) brain atrophy, (2) subcortical vascular disease, and (3) strategic infarcts (anterior-medial thalamus and cortical infarcts). After accounting for the effects of age and education, measures of brain atrophy were the strongest correlates of all cognitive domains. Small vessel disease was independently associated with general severity, impaired short-term memory/language, and reduced mental flexibility, but not with poor working memory, presumably through disruption of frontal-subcortical connections. In contrast, strategic infarcts to anterior-medial thalamus and cortical gray matter were associated with poor short-term and working memory, but not with impairments in mental flexibility or global severity measures. These data support the hypothesis that the thalamico

  19. Misidentification of Yersinia pestis by automated systems, resulting in delayed diagnoses of human plague infections--Oregon and New Mexico, 2010-2011.

    PubMed

    Tourdjman, Mathieu; Ibraheem, Mam; Brett, Meghan; Debess, Emilio; Progulske, Barbara; Ettestad, Paul; McGivern, Teresa; Petersen, Jeannine; Mead, Paul

    2012-10-01

    One human plague case was reported in Oregon in September 2010 and another in New Mexico in May 2011. Misidentification of Yersinia pestis by automated identification systems contributed to delayed diagnoses for both cases.

  20. A case of extensive left-sided facial atrophy of Romberg

    PubMed Central

    Verma, Rajesh; Ram, Hari; Gupta, Mani; Vidhate, Mukund R

    2013-01-01

    Progressive facial atrophy or Parry-Romberg syndrome is characterized by slowly progressive facial atrophy involving skin, subcutaneous tissue, cartilage and bony structures. Apart from facial atrophy, it can be associated with diverse clinical manifestations including headache, partial seizures, trigeminal neuralgia, cerebral hemiatrophy and ocular abnormalities. The exact etiology is unknown although sympathetic system dysfunction, autoimmune disorders, focal scleroderma, trauma and genetic factors have been postulated. We hereby report a patient having marked left-sided facial atrophy and wasting of the tongue. Such an extensive wasting is not previously reported in the literature. PMID:24163557

  1. Diagnosing unknown aberrations in an adaptive optics system by use of phase diversity.

    PubMed

    Lee, D J; Welsh, B M; Roggemann, M C; Ellerbroek, B L

    1997-07-01

    We outline a novel method for estimating a fixed aberration that is in the image path but not in the wave-front-sensor (WFS) path of an adaptive optics (AO) imaging system. We accomplish this through a nontraditional application of the Gonsalves [Proc. SPIE 207, 32 (1997)] least-squares phase-diversity technique, using an ensemble of images and WFS data. The diversity phases required for this technique are provided by the temporal differences in WFS residual phase measurements for different members of the ensemble. We demonstrate the technique by using actual observations from an operational AO system exhibiting such an aberration. An estimate of this aberration was obtained by the proposed algorithm that agrees reasonably well with the observed point-spread function.

  2. Sensor placement for diagnosability in space-borne systems - A model-based reasoning approach

    NASA Technical Reports Server (NTRS)

    Chien, Steve; Doyle, Richard; Rouquette, Nicolas

    1992-01-01

    This paper presents an approach to evaluating sensor placements on the basis of how well they are able to discriminate between a given fault and normal operating modes and/or other fault modes. In this approach, a model of the system in both normal operations and fault modes is used to evaluate possible sensor placements upon the basis of three criteria. Discriminability measures how much of a divergence in expected sensor readings the two system modes can be expected to produce. Accuracy measures confidence in the particular model predictions. Timeliness measures how long after the fault occurrence the expected divergence will take place. These three metrics then can be used to form a recommendation for a sensor placement. This paper describes how these measures can be computed and illustrated these methods with a brief example.

  3. Application of Expert Systems for Diagnosing Equipment Failures at Central Energy Plants

    DTIC Science & Technology

    1993-12-01

    in the industry . His knowledge about sensor placement for collecting inputs to the control system could not be incorporated into the present 31 version...34 International Workshop on Artificial Intelligence for Industrial Applications 1988 (Kyushu Electric Power Company. Inc./Toshiba Corporation, 1988...TRADOC Defease Logistica A~eacy CECPW Fort Mame 23651 ATTN: DLA-WI 72304 ATTN: CECPW-F 22060 ATTN: AThUO-G ATTN: C.CPW-TT 22060 InstIlatior: Walte

  4. Medical and patient attitude towards vaginal atrophy: the AGATA study.

    PubMed

    Palma, F; Della Vecchia, E; Cagnacci, A

    2016-12-01

    To provide data on current management of vaginal atrophy (VA) in a nationwide setting. A cross-sectional, multicenter study was made in 913 postmenopausal women consulting 22 gynecological outpatient services. VA was diagnosed with a combination of subjective symptoms and objective evaluations. Women with a previous diagnosis and those with a new diagnosis of VA filled additional questionnaires regarding modalities of VA management and reasons for missing diagnosis, respectively. 730/913 (80%) women had ever had a diagnosis of VA. In 274 (37.5%), the diagnosis was made prior to, and in 456 (62.5%) during the investigation. Of women with a new VA diagnosis, 81.1% had never discussed their symptoms with the health-care practitioner (HCP), and 78.7% (n = 359) had never been questioned by an HCP. Of women with a previous VA diagnosis, 90.2% had been treated with systemic (10.1%), local hormonal (49.4%) or local non-hormonal (30.5%) therapy. At the time of investigation, 61.9% of these women had stopped treatment, with only 3.3% having been successfully cured. VA is highly prevalent in postmenopausal women. Its current management and treatment seem to be highly unsatisfactory and can be improved by medical sensitization and patient education.

  5. The adult literacy evaluator: An intelligent computer-aided training system for diagnosing adult illiterates

    NASA Technical Reports Server (NTRS)

    Yaden, David B., Jr.

    1992-01-01

    An important part of NASA's mission involves the secondary application of its technologies in the public and private sectors. One current application being developed is The Adult Literacy Evaluator, a simulation-based diagnostic tool designed to assess the operant literacy abilities of adults having difficulties in learning to read and write. Using ICAT system technology in addition to speech recognition, closed-captioned television (CCTV), live video and other state-of-the art graphics and storage capabilities, this project attempts to overcome the negative effects of adult literacy assessment by allowing the client to interact with an intelligent computer system which simulates real-life literacy activities and materials and which measures literacy performance in the actual context of its use. The specific objectives of the project are as follows: (1) To develop a simulation-based diagnostic tool to assess adults' prior knowledge about reading and writing processes in actual contexts of application; (2) to provide a profile of readers' strengths and weaknesses; and (3) to suggest instructional strategies and materials which can be used as a beginning point for remediation. In the first and developmental phase of the project, descriptions of literacy events and environments are being written and functional literacy documents analyzed for their components. Examples of literacy events and situations being considered included interactions with environmental print (e.g., billboards, street signs, commercial marquees, storefront logos, etc.), functional literacy materials (e.g., newspapers, magazines, telephone books, bills, receipts, etc.) and employment related communication (i.e., job descriptions, application forms, technical manuals, memorandums, newsletters, etc.). Each of these situations and materials is being analyzed for its literacy requirements in terms of written display (i.e., knowledge of printed forms and conventions), meaning demands (i

  6. How to Diagnose and Classify Tattoo Complications in the Clinic: A System of Distinctive Patterns.

    PubMed

    Serup, Jørgen

    2017-01-01

    Tattoo complications represent a broad spectrum of clinical entities and disease mechanisms. Infections are known, but chronic inflammatory reactions have hitherto been inconsistently reported and given many interpretations and terms. A clinical classification system of distinct patterns with emphasis on inflammatory tattoo reactions is introduced. Allergic reactions prevalent in red tattoos and often associated with azo pigments are manifested as the 'plaque elevation', 'excessive hyperkeratosis', and 'ulceronecrotic' patterns. The allergen is a hapten. Nonallergic reactions prevalent in black tattoos and associated with carbon black are manifested as the 'papulonodular' pattern. Carbon black nanoparticles agglomerate in the dermis over time forming foreign bodies that elicit reactions. Many black tattoos even develop sarcoid granuloma, and the 'papulonodular' pattern is strongly associated with sarcoidosis affecting other organs. Tattoo complications include a large group of less frequent but nevertheless specific entities, i.e. irritant and toxic local events, photosensitivity, urticaria, eczematous rash due to soluble allergen, neurosensitivity and pain syndrome, lymphopathies, pigment diffusion or fan, scars, and other sequels of tattooing or tattoo removal. Keratoacanthoma occurs in tattoos. Carcinoma and melanoma are rare and occur by coincidence only. Different tattoo complications require different therapeutic approaches, and precise diagnosis is thus important as a key to therapy. The proposed new classification with characteristic patterns relies on simple tools, namely patient history, objective findings, and supplementary punch biopsy. By virtue of simplicity and broad access, these methods make the proposed classification widely applicable in clinics and hospitals. The system is reported to the 11th revision of the WHO diagnosis classification used as international standard. © 2017 S. Karger AG, Basel.

  7. Diagnosing and Managing Violence

    PubMed Central

    2011-01-01

    Available categorization systems for violence encountered in medical practice do not constitute optimal tools to guide management. In this article, 4 common patterns of violence across psychiatric diagnoses are described (defensive, dominance-defining, impulsive, and calculated) and management implications are considered. The phenomenologic and neurobiological rationale for a clinical classification system of violence is also presented. PMID:22295257

  8. A Boolean Consistent Fuzzy Inference System for Diagnosing Diseases and Its Application for Determining Peritonitis Likelihood

    PubMed Central

    Dragović, Ivana; Turajlić, Nina; Pilčević, Dejan; Petrović, Bratislav; Radojević, Dragan

    2015-01-01

    Fuzzy inference systems (FIS) enable automated assessment and reasoning in a logically consistent manner akin to the way in which humans reason. However, since no conventional fuzzy set theory is in the Boolean frame, it is proposed that Boolean consistent fuzzy logic should be used in the evaluation of rules. The main distinction of this approach is that it requires the execution of a set of structural transformations before the actual values can be introduced, which can, in certain cases, lead to different results. While a Boolean consistent FIS could be used for establishing the diagnostic criteria for any given disease, in this paper it is applied for determining the likelihood of peritonitis, as the leading complication of peritoneal dialysis (PD). Given that patients could be located far away from healthcare institutions (as peritoneal dialysis is a form of home dialysis) the proposed Boolean consistent FIS would enable patients to easily estimate the likelihood of them having peritonitis (where a high likelihood would suggest that prompt treatment is indicated), when medical experts are not close at hand. PMID:27069500

  9. Mechanisms of Muscle Growth and Atrophy in Mammals and Drosophila

    PubMed Central

    Piccirillo, Rosanna; Demontis, Fabio; Perrimon, Norbert; Goldberg, Alfred L.

    2014-01-01

    The loss of skeletal muscle mass (atrophy) that accompanies disuse and systemic diseases is highly debilitating. Although the pathogenesis of this condition has been primarily studied in mammals, Drosophila is emerging as an attractive system to investigate some of the mechanisms involved in muscle growth and atrophy. In this review, we highlight the outstanding unsolved questions that may benefit from a combination of studies in both flies and mammals. In particular, we discuss how different environmental stimuli and signaling pathways influence muscle mass and strength and how a variety of disease states can cause muscle wasting. PMID:24038488

  10. Assessment of strategies for identifying diagnosed cases of systemic lupus erythematosus through self-report.

    PubMed

    McAlindon, T E; Formica, M; Palmer, J R; Lafyatis, R; Rosenberg, L

    2003-01-01

    The objective of this work was to assess the optimal way to identify potential systemic lupus erythematosus (SLE) cases in large epidemiologic studies through self-reported information about diagnosis of SLE, symptoms and medications, and to investigate the utility of a criteria checklist sent directly to participants' physicians. We used data collected in 1997 from 53322 participants in a study of African-American women, the Black Women's Health Study, including a lupus screening questionnaire (LSQ) and questions about SLE diagnosis and medications. We confirmed self-reported SLE through medical records and criteria checklists sent to participants' physicians. Among those for whom we received medical records and/or criteria checklists, we compared the predictive value and proportion of missed cases of several algorithms using combinations of self-reported SLE diagnosis, LSQ score and medication use to self-reported SLE diagnosis alone. We obtained a physician checklist or medical chart for 251 individuals who reported SLE, of whom 212 (84%) fulfilled ACR criteria for definite or probable SLE, or had clinical lupus (SLE diagnosis recorded in medical charts plus appropriate medication use). The use of LSQ score or medication use in addition to self-report of SLE tended to decrease the false positive rate but also to reduce the proportion of true cases identified. Checklists of ACR criteria completed by subjects' physicians documented more criteria than medical records. In conclusion, among participants who consented to medical record review, SLE prediction algorithms using questions about lupus symptoms and medications offered slightly higher predictive value for detecting cases than self-reported diagnosis alone, but at the cost of case detection. SLE case confirmation strategies can be complemented by the use of criteria checklists sent directly to participants' physicians.

  11. Validity of COPD diagnoses reported through nationwide health insurance systems in the People’s Republic of China

    PubMed Central

    Kurmi, Om P; Vaucher, Julien; Xiao, Dan; Holmes, Michael V; Guo, Yu; Davis, Kourtney J; Wang, Chen; Qin, Haiyan; Turnbull, Iain; Peng, Peng; Bian, Zheng; Clarke, Robert; Li, Liming; Chen, Yiping; Chen, Zhengming

    2016-01-01

    Background COPD is the fourth leading cause of death worldwide, with particularly high rates in the People’s Republic of China, even among never smokers. Large population-based cohort studies should allow for reliable assessment of the determinants of diseases, which is dependent on the quality of disease diagnoses. We assessed the validity of COPD diagnoses collected through electronic health records in the People’s Republic of China. Methods The CKB study recruited 0.5 million adults aged 30–79 years from ten diverse regions in the People’s Republic of China during the period 2004–2008. During 7 years of follow-up, 11,800 COPD cases were identified by linkage with mortality registries and the national health insurance system. We randomly selected ~10% of the reported COPD cases and then undertook an independent adjudication of retrieved hospital medical records in 1,069 cases. Results Overall, these 1,069 cases were accrued over a 9-year period (2004–2013) involving 153 hospitals across ten regions. A diagnosis of COPD was confirmed in 911 (85%) cases, corresponding to a positive predictive value of 85% (95% confidence interval [CI]: 83%–87%), even though spirometry testing was not widely used (14%) in routine hospital care. The positive predictive value for COPD did not vary significantly by hospital ranking or calendar period, but was higher in men than women (89% vs 79%), at age ≥70 years than in younger people (88%, 95% CI: 85%–91%), and when the cases were reported from both death registry and health insurance systems (97%, 95% CI: 94%–100%). Among the remaining cases, 87 (8.1%) had other respiratory diseases (chiefly pneumonia and asthma; n=85) and 71 (6.6%) cases showed no evidence of any respiratory disease on their clinical records. Conclusion In the People’s Republic of China, COPD diagnoses obtained from electronic health records are of good quality and suitable for large population-based studies and do not warrant systematic

  12. PERSONALITY TRAITS, ANGER AND PSYCHIATRIC SYMPTOMS RELATED TO QUALITY OF LIFE IN PATIENTS WITH NEWLY DIAGNOSED DIGESTIVE SYSTEM CANCER.

    PubMed

    Honorato, Noemi Peres; Abumusse, Luciene Vaccaro de Morais; Coqueiro, Daniel Pereira; Citero, Vanessa de Albuquerque

    2017-01-01

    The presence of psychiatric symptoms, anger, and personality characteristics are factors that affect the quality of life of newly diagnosed digestive system cancer patients. This study aims to identify which stable characteristics of the individual's personality interfere with quality of life, even when reactive emotional characteristics of falling ill are controlled. A cross-sectional study was performed at the Oncology Clinic ( Hospital das Clínicas ), Marília/SP, Brazil, in which 50 adult patients with digestive system cancer and diagnosed less than 6 months answered the State-Trait Anger Expression Inventory, Temperament and Character Inventory, Hospital Anxiety and Depression Scale and WHOQOL-BREF. Multiple regression was performed to verify if quality of life was related to stable characteristics of the subject's personality (anger trait, temperament and character) after controlling to the transient emotional aspects (anger state, psychiatric symptoms). The quality of life psychological health score was higher in presence of self-directedness character and reward dependence temperament and quality of life environment score was higher in presence of self-directedness character and lower in presence of harm avoidance temperament. The psychological well-being and the adaptive needs to the environment that favoring a better quality of life were reinforced mainly by the self-directedness character; which means that patients more autonomous cope better with the disease. On the other hand, the harm avoidance temperament (meaning the patient has fear of aversive situations) impaired the adaptive capacity to deal with the changes of the day-to-day imposed by the disease. Understanding these personality traits is important to the health professionals drive the patient to more successful treatment.

  13. Spinal Muscular Atrophy Type I: Is It Ethical to Standardize Supportive Care Intervention in Clinical Trials?

    PubMed

    Finkel, Richard S; Bishop, Kathie M; Nelson, Robert M

    2017-02-01

    The natural history of spinal muscular atrophy type I (SMA-I) has changed as improved medical support has become available. With investigational drugs for spinal muscular atrophy now in clinical trials, efficient trial design focuses on enrolling recently diagnosed infants, providing best available supportive care, and minimizing subject variation. The quandary has arisen whether it is ethically appropriate to specify a predefined level of nutritional and/or ventilation support for spinal muscular atrophy type I subjects while participating in these studies. We conducted a survey at 2 spinal muscular atrophy investigator meetings involving physician investigators, clinical evaluators, and study coordinators from North America, Europe, and Asia-Pacific. Each group endorsed the concept that having a predefined degree of nutritional and ventilation support was warranted in this context. We discuss how autonomy, beneficence/non-maleficence, noncoercion, social benefit, and equipoise can be maintained when a predefined level of supportive care is proposed, for participation in a clinical trial.

  14. [Duodenal villous atrophy, an unexpectedly common finding in giardia lamblia infestation].

    PubMed

    Arévalo, Fernando; Aragón, Violeta; Morales L, Domingo; Morales Caramutti, Domingo; Arandia, Jannitza; Alcocer, Gabriel

    2010-01-01

    To study the histological changes observed in Giardia positive biopsies obtained from the duodenum.: The number of intraepithelial lymphocytes (IEL), grade of villous atrophy, presence of lymph follicles and number of eosinophils in the lamina propria per HPF were assessed. All giardia positive biopsies diagnosed during period 2005-2009 in 5 pathology units were reevaluated by a group of pathologists. Thirty cases were included. Atrophic villous architecture was seen in 61,2%, increase in number of intraepithelial lymphocytes in 63,3% The occurrence of lymphoid follicles in 43,3%. Villous atrophy was higher than reported by others authors, cases with atrophy showed greater frequency of increase in the number of intraepithelial lymphocytes than cases without atrophy. No cases with lymph follicle showed lack of plasmatic cells, the number of eosinophils was subtly increased.

  15. Spinal Muscular Atrophy Type I: Is It Ethical to Standardize Supportive Care Intervention in Clinical Trials?

    PubMed Central

    Finkel, Richard S.; Bishop, Kathie M.; Nelson, Robert M.

    2016-01-01

    The natural history of spinal muscular atrophy type I (SMA-I) has changed as improved medical support has become available. With investigational drugs for spinal muscular atrophy now in clinical trials, efficient trial design focuses on enrolling recently diagnosed infants, providing best available supportive care, and minimizing subject variation. The quandary has arisen whether it is ethically appropriate to specify a predefined level of nutritional and/or ventilation support for spinal muscular atrophy type I subjects while participating in these studies. We conducted a survey at 2 spinal muscular atrophy investigator meetings involving physician investigators, clinical evaluators, and study coordinators from North America, Europe, and Asia-Pacific. Each group endorsed the concept that having a predefined degree of nutritional and ventilation support was warranted in this context. We discuss how autonomy, beneficence/non-maleficence, noncoercion, social benefit, and equipoise can be maintained when a predefined level of supportive care is proposed, for participation in a clinical trial. PMID:27760875

  16. Mitochondrial signaling contributes to disuse muscle atrophy

    PubMed Central

    Wiggs, Michael P.; Duarte, Jose A.; Zergeroglu, A. Murat; Demirel, Haydar A.

    2012-01-01

    It is well established that long durations of bed rest, limb immobilization, or reduced activity in respiratory muscles during mechanical ventilation results in skeletal muscle atrophy in humans and other animals. The idea that mitochondrial damage/dysfunction contributes to disuse muscle atrophy originated over 40 years ago. These early studies were largely descriptive and did not provide unequivocal evidence that mitochondria play a primary role in disuse muscle atrophy. However, recent experiments have provided direct evidence connecting mitochondrial dysfunction to muscle atrophy. Numerous studies have described changes in mitochondria shape, number, and function in skeletal muscles exposed to prolonged periods of inactivity. Furthermore, recent evidence indicates that increased mitochondrial ROS production plays a key signaling role in both immobilization-induced limb muscle atrophy and diaphragmatic atrophy occurring during prolonged mechanical ventilation. Moreover, new evidence reveals that, during denervation-induced muscle atrophy, increased mitochondrial fragmentation due to fission is a required signaling event that activates the AMPK-FoxO3 signaling axis, which induces the expression of atrophy genes, protein breakdown, and ultimately muscle atrophy. Collectively, these findings highlight the importance of future research to better understand the mitochondrial signaling mechanisms that contribute to disuse muscle atrophy and to develop novel therapeutic interventions for prevention of inactivity-induced skeletal muscle atrophy. PMID:22395111

  17. Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother.

    PubMed

    Kocaoglu, Celebi; Akin, Fatih; Caksen, Hüseyin; Böke, Saltuk Buğra; Arslan, Sükrü; Aygün, Serhat

    2014-06-01

    In developed countries, vitamin B12 (cobalamin) deficiency usually occurs in children, exclusively breastfed ones whose mothers are vegetarian, causing low body stores of vitamin B12. The haematologic manifestation of vitamin B12 deficiency is pernicious anaemia. It is a megaloblastic anaemia with high mean corpuscular volume and typical morphological features, such as hyperlobulation of the nuclei of the granulocytes. In advanced cases, neutropaenia and thrombocytopaenia can occur, simulating aplastic anaemia or leukaemia. In addition to haematological symptoms, infants may experience weakness, fatigue, failure to thrive, and irritability. Other common findings include pallor, glossitis, vomiting, diarrhoea, and icterus. Neurological symptoms may affect the central nervous system and, in severe cases, rarely cause brain atrophy. Here, we report an interesting case, a 12-month old infant, who was admitted with neurological symptoms and diagnosed with vitamin B12 deficiency.

  18. Diseases of the circulatory system among adult people diagnosed with infantile autism as children: A longitudinal case control study.

    PubMed

    Mouridsen, Svend Erik; Rich, Bente; Isager, Torben

    2016-10-01

    Research dealing with adult people with autism spectrum disorders (ASD) noticeably lags behind studies of children and young individuals with ASD. The objective of this study was to compare the prevalence and types of diseases of the circulatory system in a clinical sample of 118 adult people diagnosed with infantile autism (IA) as children with 336 sex and age matched controls from the general population. All participants were screened through the nationwide Danish National Hospital Register. The average observation time of both groups was 37.2 years, and mean age at follow-up was 49.6 years. Of the 118 people with IA, 11 (9.3%) were registered with at least one disease of the circulatory system against 54 (16.1%) in the comparison group (p=0.09; OR=0.54; 95% CI 0.3-1.2). Ischemic heart diseases occurred significantly more frequently among people in the comparison group (p=0.02). It is argued that diseases of the circulatory system may be underdiagnosed in people with IA because of the difficulties they face with respect to identifying and communicating symptoms of ill health. Bearing in mind that cardiovascular disease is the primary cause of death in most developed countries, it is suggested that to prevent disease and manage health conditions, health monitoring is essential in adult people with IA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Spinal Muscular Atrophy (SMA)

    MedlinePlus

    ... children with SMA develop spinal deformities, such as scoliosis (sideways curvature of the spine) and kyphosis (front- ... Magnetic Resonance Imaging (MRI) Brain and Nervous System Scoliosis Contact Us Print Resources Send to a friend ...

  20. Progressive Hemifacial Atrophy With Contralateral Uveitis: A Case Report

    PubMed Central

    Ayyildiz, Onder; Ayyildiz, Simel; Durukan, Ali Hakan; Sobaci, Gungor

    2015-01-01

    Introduction: Progressive hemifacial atrophy, known as Parry-Romberg syndrome (PRS), was first described by Parry in 1825. There is a progressive atrophy of facial tissues including skin, bones and muscles. Ophthalmic disorders are common and include keratitis, uveitis, cataract, ipsilateral enophthalmos, optic neuritis, retinal vasculitis and scleral melting. Case Presentation: We describe a patient with progressive hemifacial atrophy at right facial side who developed granulomatous uveitis and periferic retinal vasculitis in his left eye. We started topical and systemic steroid therapy. Uveitic reaction had regressed almost entirely after a 3-month steroid treatment. Conclusions: The individuals should have multidisciplinary approach for the variety of disorders to maintain the appropriate treatment for a better appearance of the patients. PMID:26473067

  1. APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD

    PubMed Central

    Manning, Emily N.; Barnes, Josephine; Cash, David M.; Bartlett, Jonathan W.; Leung, Kelvin K.; Ourselin, Sebastien; Fox, Nick C.

    2014-01-01

    Objectives To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates. Methods MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into “progressors” (MCI-P) if diagnosed with AD within 36 months or “stable” (MCI-S) if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated. Results Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P. Conclusions These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD. PMID:24878738

  2. [A Case of Musicophilia with Right Predominant Temporal Lobe Atrophy].

    PubMed

    Shinagawa, Shunichiro; Nakayama, Kazuhiko

    2015-11-01

    A 68-year-old woman exhibiting musicophilia with right predominant temporal lobe atrophy happened to visit our clinic. She had no musical background, but beginning two years ago, she acquired a strong preference for especially popular music and sometimes sang at home. She did not exhibit obvious semantic aphasia or facial agnosia, and showed only mild behavioral changes including apathy. Her musicophilia can be explained as an instance of stereotypical behavior. Her right temporal lobe atrophy may have caused changes in her emotional and reward systems, resulting in her music specific behaviors.

  3. Postradiation atrophy of mature bone

    SciTech Connect

    Erguen, H.; Howland, W.J.

    1980-01-01

    The growing number of oncological patients subjected to radiotherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecting demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

  4. Postradiation atrophy of mature bone

    SciTech Connect

    Ergun, H.; Howland, W.J.

    1980-01-01

    The growing number of oncological patients subjected to radiotherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecing demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

  5. Mobile telecare system for intensive insulin treatment and patient education. First applications for newly diagnosed type 1 diabetic patients.

    PubMed

    Ładyzyński, P; Wójcicki, J M; Krzymień, J; Foltyński, P; Migalska-Musiał, K; Tracz, M; Karnafel, W

    2006-11-01

    The aim of the work was to develop and to evaluate the clinical efficiency of a mobile telecare system implementing teleconsultations based on the continuous transmission of patient-collected data directly to the physician and to the clinic. The developed TeleMed system consists of the patients' and the diabetologist's mobile units, the diabetologist's clinic and home workstations and the clinical server. The evaluation of the system was performed on a group of 13 newly diagnosed type 1 diabetic patients, during a single-arm study with 3-days run-in period, including a one-day intensive educational program, and 3-week study period, when the intensive insulin treatment was conducted without visits of patients to the clinic. The MBG dropped from 7.2 +/- 1.7 mmol/L before the study to 6.1 +/- 1.0 mmol/L in the third week of the study (P = 0.02) and the J-index from 30.2+/-19.2 to 19.7+/-7.7 (P = 0.04). Hemoglobin A1c decreased from 11.8 +/- 3.3% to 8.6 +/- 1.2% (P = 0.0002) in one month. The total daily insulin dose declined from 39.9 +/- 8.5 U to 20.0 +/- 9.6 U (P = 0.000006). The number of hypoglycemia episodes per patient per day decreased by 66% (P = 0.08) and the number of hyperglycemia episodes was reduced by 47% (P < 0.0001). The TeleMed facilitates not only efficient realization of the intensive insulin treatment but also successful remote patient training and education. No formal patient satisfaction study was done. However, some of the findings indicate that the application of the developed system increases patient self-confidence and quality of life.

  6. Geographic atrophy: Etiopathogenesis and current therapies.

    PubMed

    Sastre-Ibáñez, M; Barreiro-González, A; Gallego-Pinazo, R; Dolz-Marco, R; García-Armendariz, B

    2017-09-05

    Geographic atrophy is characterized by severe visual deficit whose etiology and pathophysiology are yet to be elucidated. As a working hypothesis, oxidative damage could trigger a chronic inflammation in Bruch's membrane-RPE-choriocapillaris complex, mostly due to complement pathway overactivation. Some individuals with mutations in the complement system and other factors have diminished capacity in the modulation of the inflammatory response, which results in cell damage and waste accumulation. This accumulation of intracellular and extracellular waste products manifests as drusen and pigmentary changes that precede the atrophy of photoreceptors, RPE, choriocapillaris with an ischemic process with decreased choroid flow. All these processes can be detected as tomographic findings and autofluorescence signals that are useful in the evaluation of patients with atrophic AMD, which helps to establish an individualized prognosis. Anti-inflammatory, antioxidant and therapies that decrease the accumulation of toxins for the preservation of the RPE cells and photoreceptors are being investigated in order to slow down the progression of this disease. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. RAIRS2 a new expert system for diagnosing tuberculosis with real-world tournament selection mechanism inside artificial immune recognition system.

    PubMed

    Saybani, Mahmoud Reza; Shamshirband, Shahaboddin; Golzari, Shahram; Wah, Teh Ying; Saeed, Aghabozorgi; Mat Kiah, Miss Laiha; Balas, Valentina Emilia

    2016-03-01

    Tuberculosis is a major global health problem that has been ranked as the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus. Diagnosis based on cultured specimens is the reference standard; however, results take weeks to obtain. Slow and insensitive diagnostic methods hampered the global control of tuberculosis, and scientists are looking for early detection strategies, which remain the foundation of tuberculosis control. Consequently, there is a need to develop an expert system that helps medical professionals to accurately diagnose the disease. The objective of this study is to diagnose tuberculosis using a machine learning method. Artificial immune recognition system (AIRS) has been used successfully for diagnosing various diseases. However, little effort has been undertaken to improve its classification accuracy. In order to increase the classification accuracy, this study introduces a new hybrid system that incorporates real tournament selection mechanism into the AIRS. This mechanism is used to control the population size of the model and to overcome the existing selection pressure. Patient epacris reports obtained from the Pasteur laboratory in northern Iran were used as the benchmark data set. The sample consisted of 175 records, from which 114 (65 %) were positive for TB, and the remaining 61 (35 %) were negative. The classification performance was measured through tenfold cross-validation, root-mean-square error, sensitivity, and specificity. With an accuracy of 100 %, RMSE of 0, sensitivity of 100 %, and specificity of 100 %, the proposed method was able to successfully classify tuberculosis cases. In addition, the proposed method is comparable with top classifiers used in this research.

  8. Muscle atrophy and metal-on-metal hip implants

    PubMed Central

    Berber, Reshid; Khoo, Michael; Cook, Erica; Guppy, Andrew; Hua, Jia; Miles, Jonathan; Carrington, Richard; Skinner, John; Hart, Alister

    2015-01-01

    Background and purpose Muscle atrophy is seen in patients with metal-on-metal (MOM) hip implants, probably because of inflammatory destruction of the musculo-tendon junction. However, like pseudotumors, it is unclear when atrophy occurs and whether it progresses with time. Our objective was to determine whether muscle atrophy associated with MOM hip implants progresses with time. Patients and methods We retrospectively reviewed 74 hips in 56 patients (32 of them women) using serial MRI. Median age was 59 (23–83) years. The median time post-implantation was 83 (35–142) months, and the median interval between scans was 11 months. Hip muscles were scored using the Pfirrmann system. The mean scores for muscle atrophy were compared between the first and second MRI scans. Blood cobalt and chromium concentrations were determined. Results The median blood cobalt was 6.84 (0.24–90) ppb and median chromium level was 4.42 (0.20–45) ppb. The median Oxford hip score was 34 (5–48). The change in the gluteus minimus mean atrophy score between first and second MRI was 0.12 (p = 0.002). Mean change in the gluteus medius posterior portion (unaffected by surgical approach) was 0.08 (p = 0.01) and mean change in the inferior portion was 0.10 (p = 0.05). Mean pseudotumor grade increased by 0.18 (p = 0.02). Interpretation Worsening muscle atrophy and worsening pseudotumor grade occur over a 1-year period in a substantial proportion of patients with MOM hip implants. Serial MRI helps to identify those patients who are at risk of developing worsening soft-tissue pathology. These patients should be considered for revision surgery before irreversible muscle destruction occurs. PMID:25588091

  9. Assessment of bone mineral density and bone metabolism in young male adults recently diagnosed with systemic lupus erythematosus in China.

    PubMed

    Guo, Qinyue; Fan, Ping; Luo, Jing; Wu, Shufang; Sun, Hongzhi; He, Lan; Zhou, Bo

    2017-03-01

    Objective Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. However, the exact mechanism underlying SLE-related osteopenia and osteoporosis in patients newly diagnosed with SLE remains unknown. Methods 60 male subjects with SLE aged 20-30 years were enrolled. Serum osteocalcin was examined as a marker of bone formation and type I collagen degradation products (β-crosslaps) as markers of bone resorption. Lumbar spine (L1-L4) and total hip bone mineral density (BMD) were determined by dual energy X-ray absorption (DXA). Results Among the 60 subjects with SLE at the time of diagnosis, the cohort showed a significant reduction of osteocalcin (12.62 ± 2.16 ng/mL), and serum β-crosslaps level (992.6 ± 162.6 pg/mL) was markedly elevated. Univariate correlation analyses revealed negative correlations between osteocalcin and SLEDAI, dsDNA antibody and β-crosslaps. A positive correlation was also observed between osteocalcin and C3, C4, 25-OH vitamin D, BMD L1-L4 and BMD total hip (see Table 3). Osteocalcin and β-crosslaps were strongly associated with SLE disease activity by multiple stepwise logistic regression analysis. Conclusion Osteocalcin was negatively associated with SLE disease activity, and β-crosslaps was positively associated with SLE disease activity, suggesting SLE disease activity itself directly contributed to the development of SLE-associated osteopenia and osteoporosis.

  10. [Screening of malnutrition risk versus indicators of nutritional status and systemic inflammatory response in newly diagnosed lung cancer patients].

    PubMed

    Illa, P; Tomíšková, M; Skřičková, J

    2014-01-01

    Most lung cancers are already advanced at the time of dia-gnosis. In these patients, a frequent symptom is protein energy malnutrition, often diagnosed prior to oncological treatment. Malnutrition results in poor tolerance of treatment and increased morbidity and mortality. Nutritional Risk Screening (NRS) 2002 adapted for oncological patients was used to assess the risk of undernutrition in a group of 188 lung cancer patients. The risk was evaluated on a 6- point scale according to common signs of nutritional status and tumor and its treatment risk factors. A score of 3 and more (called "nutritional risk") means a significant risk of malnutrition. Furthermore, pretreatment nutritional characteristics were evaluated in patients (including the value of BMI) and laboratory values indicating malnutrition/ acute phase response (albumin/ C reactive protein - CRP). Acceptable NRS score was found in 50.6%, while in 45.3% was suggested into risk of malnutrition ("nutritional risk"). Only 6.6% of our patients had a BMI less than 20 kg/ m2. Significant differences in albumin and CRP values in various categories of NRS were confirmed. Initial signs of cancer malnutrition may be overlooked in patients who fall within or above the range of BMI for adequate weight, although these patients may be at significant risk of malnutrition. The indicators of nutritional status and systemic inflammatory responses were significantly associated with resulting values NRS score.

  11. (18)F-FDG-PET/CT for systemic staging of newly diagnosed triple-negative breast cancer.

    PubMed

    Ulaner, Gary A; Castillo, Raychel; Goldman, Debra A; Wills, Jonathan; Riedl, Christopher C; Pinker-Domenig, Katja; Jochelson, Maxine S; Gönen, Mithat

    2016-10-01

    National Comprehensive Cancer Network guidelines recommend (18)F-FDG-PET/CT, in addition to standard staging procedures, for systemic staging of newly diagnosed stage III breast cancer patients. However, factors in addition to stage may influence PET/CT utility. As breast cancers that are negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (triple-negative breast cancer, or TNBC) are more aggressive and metastasize earlier than other breast cancers, we hypothesized that receptor expression may be one such factor. This study assesses (18)F-FDG-PET/CT for systemic staging of newly diagnosed TNBC. In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with TNBC who underwent (18)F-FDG-PET/CT in 2007-2013 prior to systemic or radiation therapy. Initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery, if performed prior to (18)F-FDG-PET/CT. (18)F-FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases, as well as unsuspected synchronous malignancies. Kaplan Meier survival estimates were calculated for initial stage IIB patients stratified by whether or not stage 4 disease was detected by (18)F-FDG-PET/CT. A total of 232 patients with TNBC met inclusion criteria. (18)F-FDG-PET/CT revealed unsuspected distant metastases in 30 (13 %): 0/23 initial stage I, 4/82 (5 %) stage IIA, 13/87 (15 %) stage IIB, 4/23 (17 %) stage IIIA, 8/14 (57 %) stage IIIB, and 1/3 (33 %) stage IIIC. Twenty-six of 30 patients upstaged to IV by (18)F-FDG-PET/CT were confirmed by pathology, with the remaining four patients confirmed by follow-up imaging. In addition, seven unsuspected synchronous malignancies were identified in six patients. Initial stage 2B patients who were upstaged to 4 by (18)F-FDG-PET/CT had significantly shorter survival compared to initial stage 2B patients who were

  12. Methylphenidate Transdermal System: A Multisite, Open-Label Study of Dermal Reactions in Pediatric Patients Diagnosed With ADHD

    PubMed Central

    Squires, Liza; Li, Yunfeng; Civil, Richard; Paller, Amy S.

    2010-01-01

    Objective: To characterize dermal reactions and examine methylphenidate (MPH) sensitization in subjects receiving methylphenidate transdermal system (MTS). Method: This multicenter, open-label, dose-optimization study utilized MTS doses of 10, 15, 20, and 30 mg in children aged 6 to 12 years, inclusive (N = 305), with a DSM-IV-TR primary diagnosis of attention-deficit/hyperactivity disorder. The study was conducted between January 8, 2007, and August 23, 2007. Subjects wore MTS on their hips for 9 hours per day, alternating sides daily for a total of 7 weeks. Assessments included the Experience of Discomfort scale, Transdermal System Adherence scale, and Dermal Response Scale (DRS; 0 = no irritation, 7 = strong reaction). On-study reevaluations were conducted to characterize DRS scores ≥ 4. Epicutaneous allergy patch testing was conducted for DRS scores ≥ 6, persistent DRS scores ≥ 4, DRS score increase following an assessment of ≥ 4, or DRS scores of 4 or 5 following elective discontinuation. Results: Approximately half of subjects experienced definite erythema at the patch site that generally dissipated within 24 hours. Four subjects experienced a DRS score of 4 (1%): erythema in 1 subject resolved on study treatment, 2 cases resolved poststudy and subjects tolerated oral MPH, and 1 subject discontinued treatment. The latter subject was referred for patch testing and was diagnosed with allergic contact sensitization to MPH. Conclusions: Few severe dermal effects were seen with MTS treatment. Dermal reactions were characterized as contact dermatitis and dissipated rapidly. On patch testing, 1 subject (0.3%) manifested sensitization to MPH. Trial Registration: clinicaltrials.gov Identifier: NCT00434213 PMID:21494336

  13. Quantitative Raman characterization of cross-linked collagen thin films as a model system for diagnosing early osteoarthritis

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Durney, Krista M.; Fomovsky, Gregory; Ateshian, Gerard A.; Vukelic, Sinisa

    2016-03-01

    The onset of osteoarthritis (OA)in articular cartilage is characterized by degradation of extracellular matrix (ECM). Specifically, breakage of cross-links between collagen fibrils in the articular cartilage leads to loss of structural integrity of the bulk tissue. Since there are no broadly accepted, non-invasive, label-free tools for diagnosing OA at its early stage, Raman spectroscopyis therefore proposed in this work as a novel, non-destructive diagnostic tool. In this study, collagen thin films were employed to act as a simplified model system of the cartilage collagen extracellular matrix. Cross-link formation was controlled via exposure to glutaraldehyde (GA), by varying exposure time and concentration levels, and Raman spectral information was collected to quantitatively characterize the cross-link assignments imparted to the collagen thin films during treatment. A novel, quantitative method was developed to analyze the Raman signal obtained from collagen thin films. Segments of Raman signal were decomposed and modeled as the sum of individual bands, providing an optimization function for subsequent curve fitting against experimental findings. Relative changes in the concentration of the GA-induced pyridinium cross-links were extracted from the model, as a function of the exposure to GA. Spatially resolved characterization enabled construction of spectral maps of the collagen thin films, which provided detailed information about the variation of cross-link formation at various locations on the specimen. Results showed that Raman spectral data correlate with glutaraldehyde treatment and therefore may be used as a proxy by which to measure loss of collagen cross-links in vivo. This study proposes a promising system of identifying onset of OA and may enable early intervention treatments that may serve to slow or prevent osteoarthritis progression.

  14. Adult celiac disease with severe or partial villous atrophy: a comparative study.

    PubMed

    Malamut, G; Matysiak-Budnik, T; Grosdider, E; Jais, J-P; Morales, E; Damotte, D; Caillat-Zucman, S; Brousse, N; Cerf-Bensussan, N; Jian, R; Cellier, C

    2008-03-01

    While severe villous atrophy (SVA) is the most typical histological feature in adult celiac disease (ACD), partial villous atrophy (PVA) is now also frequently found. So far, the impact of the severity of villous atrophy on the clinical presentation of ACD has been scarcely investigated. We aimed to compare the clinical, biological and immune features and outcomes in ACD patients presenting with PVA at diagnosis versus patients with SVA. Medical files of 48 patients with ACD diagnosed between 1992 and 2003 were retrospectively studied. The diagnosis was based on the presence of intestinal villous atrophy, with increases in intraepithelial lymphocytes and circulating celiac specific antibodies. Villous atrophy was classified as severe (subtotal and total) or partial. Symptoms, biological signs of malabsorption, immune markers, bone mineral density at diagnosis and response to gluten-free diet were recorded. At diagnosis, ten patients (four M/six F) had PVA and 38 patients (five M/33 F) had SVA, with a median age of 54 and 33 years, respectively (p<0.05). Positivity for specific antibodies, HLA typing and frequency of autoimmune disease at diagnosis were similar in both PVA and SVA patients, as was their response to gluten-free diet. Diarrhea, malabsorption syndrome and osteopenia were independent of the degree of villous atrophy. PVA was observed in 21% of patients with ACD. Except for their older age at diagnosis, patients with PVA presented with similar clinical, biological and immune characteristics and outcomes as did patients with SVA.

  15. Quantitative assessment of the degree of villous atrophy in patients with coeliac disease.

    PubMed

    Ciaccio, E J; Bhagat, G; Naiyer, A J; Hernandez, L; Green, P H R

    2008-10-01

    Endoscopy and biopsy are used to diagnose coeliac disease. There are, however, observer-dependent interpretations of the degree of villous atrophy in biopsies. A pilot study using quantitative image-processing procedures was performed to quantify the degree of villous atrophy in patients with coeliac disease. The degree of villous atrophy in duodenal biopsy images was quantified by calculating the ratio of villous edge-to-piecewise arc length (E/P ratio), and this value was compared with the blinded assessment of Marsh score for degree of villous atrophy. Mean E/P ratios for n = 31 biopsy images, 2.76 (SD 0.44) (Marsh IIIa), 1.91 (0.50) (Marsh IIIb) and 1.18 (0.22) (Marsh IIIc), were significantly different (p = 0.006). Based on non-parametric testing, the E/P ratios were inversely correlated with Marsh scores (Spearman coefficient rho = -0.798, Kendall tau = -0.681; p<0.0001). Biopsy images quantified by image analysis correlated exceedingly well with the histopathological grade of villous atrophy. Since quantified measurements are real-numbered values and lack observer bias, measurement of villous atrophy based on image analysis lends itself to standardisation of histological grading.

  16. Iris atrophy in sickle cell disease.

    PubMed Central

    Acheson, R W; Ford, S M; Maude, G H; Lyness, R W; Serjeant, G R

    1986-01-01

    Iris atrophy, of unknown origin and believed to be secondary to the vaso-occlusive process of sickle cell disease, has been observed in 25 eyes of 22 patients (two SS disease, 20 SC disease). The crude prevalence was highest in males with SC disease, in whom 14.7% of patients were affected. Iris atrophy was closely associated with proliferative sickle retinopathy in the same eye. Analysis of haematological indices failed to reveal any significant differences between patients with and without iris atrophy. The characteristics and distribution of iris atrophy are described as well as the histopathology in one 68-year-old male patient with SS disease. Images PMID:3718915

  17. Characterization of disuse skeletal muscle atrophy and the efficacy of a novel muscle atrophy countermeasure during spaceflight and simulated microgravity

    NASA Astrophysics Data System (ADS)

    Hanson, Andrea Marie

    Humans are an integral part of the engineered systems that will enable return to the Moon and eventually travel to Mars. Major advancements in countermeasure development addressing deleterious effects of microgravity and reduced gravity on the musculoskeletal system need to be made to ensure mission safety and success. The primary objectives of this dissertation are to advance the knowledge and understanding of skeletal muscle atrophy, and support development of novel countermeasures for disuse atrophy to enable healthy long-duration human spaceflight. Models simulating microgravity and actual spaceflight were used to examine the musculoskeletal adaptations during periods of unloading. Myostatin inhibition, a novel anti-atrophy drug therapy, and exercise were examined as a means of preventing and recovering from disuse atrophy. A combination of assays was used to quantify adaptation responses to unloading and examine efficacy of the countermeasures. Body and muscle masses were collected to analyze systemic changes due to treatments. Hindlimb strength and individual muscle forces were measured to demonstrate functional adaptations to treatments. Muscle fiber morphology and myosin heavy chain (MHC) expression was examined to identify adaptations at the cellular level. Protein synthesis signals insulin-like growth factor-1 (IGF-1), Akt, and p70s6 kinase; and the degradation signals Atrogin-1 and MuRF-1 were examined to identify adaptations at the molecular level that ultimately lead to muscle hypertrophy and atrophy. A time course study provided a thorough characterization of the adaptation of skeletal muscle during unloading in C57BL/6 mice, and baseline data for comparison to and evaluation of subsequent studies. Time points defining the on-set and endpoints of disuse muscle atrophy were identified to enable characterization of rapid vs. long-term responses of skeletal muscle to hindlimb suspension. Unloading-induced atrophy primarily resulted from increased protein

  18. CHOD/BVAM Chemotherapy and Whole-Brain Radiotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma

    SciTech Connect

    Laack, Nadia N.; O'Neill, Brian Patrick; Ballman, Karla V.; O'Fallon, Judith Rich; Carrero, Xiomara W.; Kurtin, Paul J.; Scheithauer, Bernd W.; Brown, Paul D.; Habermann, Thomas M.; Colgan, Joseph P.; Gilbert, Mark R.; Hawkins, Roland B.; Morton, Roscoe F.; Windschitl, Harry E.; Fitch, Tom R.; Pajon, Eduardo R.

    2011-10-01

    Purpose: To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients 70 years old and younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint was 1-year survival. Results: Thirty-six patients (19 men, 17 women) enrolled between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty (83%) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1. All 36 patients were eligible for survival and response evaluations. Median time to progression was 12.3 months, and median survival was 18.5 months. The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%, respectively. The best response was complete response in 10 patients and immediate progression in 7 patients. Ten (28%) patients had at least one grade 3 or higher neurologic toxicity. Conclusions: This regimen did improve the survival of PCNSL patients but also caused substantial toxicity. The improvement in survival is less than that reported with high-dose methotrexate-based therapies.

  19. Early Warning Implementation Guide: "Using the Massachusetts Early Warning Indicator System (EWIS) and Local Data to Identify, Diagnose, Support, and Monitor Students in Grades 1-12"

    ERIC Educational Resources Information Center

    Massachusetts Department of Elementary and Secondary Education, 2014

    2014-01-01

    The purpose of this guide is to provide information on how to use early warning data, including the Massachusetts Early Warning Indicator System (EWIS), to identify, diagnose, support and monitor students in grades 1-12. It offers educators an overview of EWIS and how to effectively use these data in conjunction with local data by following a…

  20. Neuronal involvement in muscular atrophy.

    PubMed

    Cisterna, Bruno A; Cardozo, Christopher; Sáez, Juan C

    2014-01-01

    The innervation of skeletal myofibers exerts a crucial influence on the maintenance of muscle tone and normal operation. Consequently, denervated myofibers manifest atrophy, which is preceded by an increase in sarcolemma permeability. Recently, de novo expression of hemichannels (HCs) formed by connexins (Cxs) and other none selective channels, including P2X7 receptors (P2X7Rs), and transient receptor potential, sub-family V, member 2 (TRPV2) channels was demonstrated in denervated fast skeletal muscles. The denervation-induced atrophy was drastically reduced in denervated muscles deficient in Cxs 43 and 45. Nonetheless, the transduction mechanism by which the nerve represses the expression of the above mentioned non-selective channels remains unknown. The paracrine action of extracellular signaling molecules including ATP, neurotrophic factors (i.e., brain-derived neurotrophic factor (BDNF)), agrin/LDL receptor-related protein 4 (Lrp4)/muscle-specific receptor kinase (MuSK) and acetylcholine (Ach) are among the possible signals for repression for connexin expression. This review discusses the possible role of relevant factors in maintaining the normal functioning of fast skeletal muscles and suppression of connexin hemichannel expression.

  1. Bone and Spinal Muscular Atrophy.

    PubMed

    Vai, Silvia; Bianchi, Maria Luisa; Moroni, Isabella; Mastella, Chiara; Broggi, Francesca; Morandi, Lucia; Arnoldi, Maria Teresa; Bussolino, Chiara; Baranello, Giovanni

    2015-10-01

    Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disease, leading to progressive denervation atrophy in the involved skeletal muscles. Bone status has been poorly studied. We assessed bone metabolism, bone mineral density (BMD) and fractures in 30 children (age range 15-171 months) affected by SMA types 2 and 3. Eighteen children (60%) had higher than normal levels of CTx (bone resorption marker); 25-OH vitamin D was in the lower range of normal (below 20 ng/ml in 9 children and below 12 ng/ml in 2). Lumbar spine BMAD (bone mineral apparent density) Z-score was below -1.5 in 50% of children. According to clinical records, four children had sustained four peripheral fractures; on spine X-rays, we observed 9 previously undiagnosed vertebral fractures in 7 children. There was a significant inverse regression between PTH and 25-OH D levels, and a significant regression between BMC and BMAD values and the scores of motor-functional tests. Even if this study could not establish the pathogenesis of bone derangements in SMA, its main findings - reduced bone density, low 25OH vitamin D levels, increased bone resorption markers and asymptomatic vertebral fractures also in very young patients - strongly suggest that even young subjects affected by SMA should be considered at risk of osteopenia and even osteoporosis and fractures. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. [Visual impairment in juvenile diabetes mellitus due to optic atrophy: Wolfram's syndrome].

    PubMed

    Immink, Annelies; Reeser, H Maarten; Brus, Frank

    2010-01-01

    Wolfram's syndrome is a rare neurodegenerative disorder, which usually first manifests itself around the age of 6 years. The diagnosis can be made based on the characteristics incorporated in the 'DIDMOAD' acronym: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. We present 2 boys, diagnosed with diabetes mellitus at the age of 5 and 4 years respectively. Both children developed optic atrophy over the years. These 2 cases illustrate that alongside diabetic retinopathy, possible syndromes, such as Wolfram's syndrome, should also be considered in children with diabetes mellitus and visual impairment.

  3. Crustacean muscles: atrophy and regeneration during molting

    SciTech Connect

    Mykles, D.L.; Skinner, D.M.

    1981-01-01

    The ultrastructural basis of atrophy of claw closer muscle of the land crab and the organization of myofibrils and sacroplasmic reticulum during the hydrolysis of protein that occurs during proecdysis was examined. The changes that occur in contractile proteins during claw muscle atrophy and the involvement of Ca/sup 2 +/-dependent proteinases (CDP) in myofilament degradation were investigated. (ACR)

  4. Calpain and caspase-3 play required roles in immobilization-induced limb muscle atrophy.

    PubMed

    Talbert, Erin E; Smuder, Ashley J; Min, Kisuk; Kwon, Oh Sung; Powers, Scott K

    2013-05-15

    Prolonged skeletal muscle inactivity results in a rapid decrease in fiber size, primarily due to accelerated proteolysis. Although several proteases are known to contribute to disuse muscle atrophy, the ubiquitin proteasome system is often considered the most important proteolytic system during many conditions that promote muscle wasting. Emerging evidence suggests that calpain and caspase-3 may also play key roles in inactivity-induced atrophy of respiratory muscles, but it remains unknown if these proteases are essential for disuse atrophy in limb skeletal muscles. Therefore, we tested the hypothesis that activation of both calpain and caspase-3 is required for locomotor muscle atrophy induced by hindlimb immobilization. Seven days of immobilization (i.e., limb casting) promoted significant atrophy in type I muscle fibers of the rat soleus muscle. Independent pharmacological inhibition of calpain or caspase-3 prevented this casting-induced atrophy. Interestingly, inhibition of calpain activity also prevented caspase-3 activation, and, conversely, inhibition of caspase-3 prevented calpain activation. These findings indicate that a regulatory cross talk exists between these proteases and provide the first evidence that the activation of calpain and caspase-3 is required for inactivity-induced limb muscle atrophy.

  5. Patchy villous atrophy in adult patients with suspected gluten-sensitive enteropathy: is a multiple duodenal biopsy strategy appropriate?

    PubMed

    Hopper, A D; Cross, S S; Sanders, D S

    2008-03-01

    The current internationally accepted gold standard for diagnosing celiac disease is a small-bowel biopsy demonstrating villous atrophy. However, it has been suggested that the diagnosis might not be considered as confirmed if the villous atrophy is patchy. Our aim was to assess whether there is an optimal duodenal biopsy strategy for detecting villous atrophy in adult patients with suspected gluten-sensitive enteropathy. Patients who had positive endomysial or tissue transglutaminase antibodies were prospectively recruited. Nine biopsies were taken from the duodenum: one from the duodenal bulb, four from the proximal duodenum, and four from the distal duodenum. Each biopsy was graded according to the Marsh criteria. All possible biopsy regimes were evaluated for their ability to detect the presence and severity of villous atrophy. A total of 56 patients were recruited (23 men [41 %], 33 women [59 %]; mean age 47, range 16 - 85): 53/56 patients had villous atrophy present in at least one biopsy; 10/53 patients had biopsy specimens that showed "patchy" villous atrophy. In all 53 patients with villous atrophy this was detected by taking a minimum of three biopsies (sensitivity 100 %, 95 % confidence interval [CI] 93.2 % - 100 %). However, this strategy always incorporated a duodenal bulb biopsy. The most severe degree of villous atrophy in all 56 patients was only detected by using a five-biopsy regime (sensitivity 100 %, 95 % CI 93.6 % - 100 %). In this study we observed that villous atrophy in adult patients with suspected gluten-sensitive enteropathy (antibody-positive) is patchy. For this reason we would suggest a minimum of three biopsies, incorporating a duodenal bulb biopsy, to ensure that villous atrophy is detected. However, a five-biopsy regime is required for recognition of the most severe lesion.

  6. Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge.

    PubMed

    Martins, Cláudio; Teixeira, Cristina; Ribeiro, Suzane; Trabulo, Daniel; Cardoso, Cláudia; Mangualde, João; Freire, Ricardo; Alves, Ana Luísa; Gamito, Élia; Cremers, Isabelle; Oliveira, Ana Paula

    2016-01-01

    Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described-olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy.

  7. Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge

    PubMed Central

    Teixeira, Cristina; Ribeiro, Suzane; Trabulo, Daniel; Cardoso, Cláudia; Mangualde, João; Freire, Ricardo; Alves, Ana Luísa; Gamito, Élia; Cremers, Isabelle; Oliveira, Ana Paula

    2016-01-01

    Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described—olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy. PMID:27803820

  8. Carrier testing for spinal muscular atrophy

    PubMed Central

    Gitlin, Jonathan M.; Fischbeck, Kenneth; Crawford, Thomas O.; Cwik, Valerie; Fleischman, Alan; Gonye, Karla; Heine, Deborah; Hobby, Kenneth; Kaufmann, Petra; Keiles, Steven; MacKenzie, Alex; Musci, Thomas; Prior, Thomas; Lloyd-Puryear, Michele; Sugarman, Elaine A.; Terry, Sharon F.; Urv, Tiina; Wang, Ching; Watson, Michael; Yaron, Yuval; Frosst, Phyllis; Howell, R. Rodney

    2014-01-01

    Spinal muscular atrophy is the most common fatal hereditary disease among newborns and infants. There is as yet no effective treatment. Although a carrier test is available, currently there is disagreement among professional medical societies who proffer standards of care as to whether or not carrier screening for spinal muscular atrophy should be offered as part of routine reproductive care. This leaves health care providers without clear guidance. In fall 2009, a meeting was held by National Institutes of Health to examine the scientific basis for spinal muscular atrophy carrier screening and to consider the issues that accompany such screening. In this article, the meeting participants summarize the discussions and conclude that pan-ethnic carrier screening for spinal muscular atrophy is technically feasible and that the specific study of implementing a spinal muscular atrophy carrier screening program raises broader issues about determining the scope and specifics of carrier screening in general. PMID:20808230

  9. How Is Asthma Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Asthma Diagnosed? Your primary care doctor will diagnose asthma ... other disease may be causing your symptoms. Diagnosing Asthma in Young Children Most children who have asthma ...

  10. Is hippocampal atrophy a future drug target?

    PubMed

    Dhikav, Vikas; Anand, Kuljeet Singh

    2007-01-01

    Hippocampus is the brain structure, vital for episodic and declarative memory. Atrophy of the human hippocampus is seen in a variety of psychiatric and neurological disorders e.g. recurrent depression, schizophrenia, bipolar disorder, post-traumatic stress disorder, epilepsy, head injury, and Alzheimer's disease (AD). Importantly, aging hippocampus also undergoes atrophy. In many instances, for example, AD, the atrophy precedes the development of symptoms while in others, there is a temporal relationship between atrophy and symptomatology. The presence of atrophied hippocampus is one of the most consistent features of many common psychiatric disorders. Several factors contribute to this atrophy. Stress is one of the most profound factors implicated and the mechanisms involve glucocorticoids, serotonin, excitatory amino acids etc. Hippocampal formation as a whole can undergo atrophy or its individual structural components e.g. apical dendrities can exhibit atrophy. Several drugs of unrelated classes have been shown to prevent atrophy indicating heterogenous manner in which hippocampal atrophy is produced. These include, tianeptine (affects structural plasticity in hippocampus and is an effective antidepressant); phenytoin (antiseizure and neuroprotective); fluoxetine (downregulates neurodegenerative enzyme and increases neuroprotective hippocampal S100 beta); lithium (neuroprotective and antiapoptotic); tricyclic antidepressants (increase hippocampal neurogenesis); antipsychotics (reduce hippocampal neuronal suppression); sodium valproate (increases neurogenesis) and mifepristone (antioxidant, neuroprotective and anti-glucocorticoid). Now the most important question is: to what extent does the hippocampal atrophy play a role in the genesis of symptoms of diseases or their progression? And if it does, can we achieve the same degree of prevention or reversal seen in experimental animals, in humans also. An even more important question is: whether the prevention of

  11. Spinal muscular atrophy (SMA) after conception using gametes from anonymous donors: recommendations for the future.

    PubMed

    Callum, Pamela; Urbina, Maria Teresa; Falk, Rena E; Alvarez-Diaz, Jorge A; Benjamin, Isaac; Sims, Charles A

    2010-02-01

    To discuss the diagnosis of spinal muscular atrophy in a child conceived using donor gametes. None. None. Offspring of gamete donors. None. None. A child conceived using gametes from anonymous sperm and ova donors was diagnosed with spinal muscular atrophy type 1. Gamete donor facilities are not required to perform extensive genetic testing on their donors; however, the well-being of the children conceived through assisted reproductive technologies should be a primary objective of reproductive medicine. The risk for specific medical problems in donor offspring can be significantly reduced by incorporating carrier screening for common, severe disorders such as spinal muscular atrophy into donor screening practices. Future efforts should focus on communicating the limitations of genetic screening to donor gamete recipients and educating them about their reproductive options. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Histopathology and the detection of avian bornavirus in the nervous system of birds diagnosed with proventricular dilatation disease.

    PubMed

    Ouyang, N; Storts, R; Tian, Y; Wigle, W; Villanueva, I; Mirhosseini, N; Payne, S; Gray, P; Tizard, I

    2009-10-01

    Avian bornavirus (ABV) is currently considered a probable etiologic agent of proventricular dilatation disease (PDD) of psittacines. We tested 24 stored avian brain samples, processed for histopathology and retained following their submission for necropsy or histopathology to the Schubot Exotic Bird Center diagnostic laboratory in 1992. Thirteen of these samples were from birds diagnosed at that time as suffering from PDD. The remaining 11 samples were diagnosed as suffering from diseases other than PDD. Immunohistochemistry was performed using an antiserum directed against the ABV nucleoprotein (N-protein). Stained slides were read by an investigator unaware of their prior histopathology results. Cells containing ABV N-protein were present in the nervous tissues of all 13 PDD cases. One bird not previously diagnosed with PDD also had ABV N-protein in its brain. A review of this bird's necropsy report indicated that it was, most probably, also suffering from PDD. The remaining 10 non-PDD birds had no detectable N-protein in their brains. The N-protein was present in the cerebrum, cerebellum and spinal cord. These findings support other studies that indicate that ABV is an etiological agent of PDD.

  13. Progression of Macular Atrophy in Pattern Dystrophies.

    PubMed

    Pallado, Céline Mebsout; Sikorav, Anne; Semoun, Oudy; Jung, Camille; Souied, Eric H

    2016-07-01

    To quantify the progression of macular atrophy associated with pattern dystrophies (PD). Retrospective, observational study including patients with reticular PD and macular atrophy. A detailed ophthalmologic exam was performed, and progression of macular atrophy areas was evaluated on fundus autofluorescence frames using RegionFinder software, a semiautomated software embedded in Spectralis device (Heidelberg Engineering, Heidelberg, Germany). We included 19 eyes of 12 patients. The median follow-up was 4.5 years (interquartile range [IQR]: 2.7-5.5). Three eyes (16%) had choroidal neovascularization. Atrophy involved foveal area in 21% (four of 19) of cases. Decreased vision occurred in three eyes (16%). The median atrophy progression rate evaluated by RegionFinder software was 0.101 mm(2)/year (IQR: 0.054-0.257). The progression of macular atrophy in PDs appears to be relatively slow. Further studies are necessary to correlate the progression of atrophy in PDs with genetic data. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:652-658.]. Copyright 2016, SLACK