Neurodegenerative Diseases最新文献

{"title":"What Shall We Do for the Patients with Shaky Leg Syndrome? A Review of 23 Patients.","authors":"Sangmin Park,&nbsp;Jung Geol Lim,&nbsp;Hee Jin Chang,&nbsp;Eungseok Oh","doi":"10.1159/000509411","DOIUrl":"https://doi.org/10.1159/000509411","url":null,"abstract":"<p><p>Orthostatic tremor (OT) is not an uncommon symptom in various neurodegenerative diseases. However, the nature and pathophysiology of OT involve a complex network of tremors and dopaminergic pathways. We assessed patients who complained of prominent leg tremors described as \"shaky leg.\" We analyzed their characteristics and evaluated them with neuroimaging and electrophysiological tools. A total of 23 patients who experienced an uncomfortable symptom of leg tremor were retrospectively enrolled from April 2014 to October 2019. Previous medical history, brain MRI, and surface electromyography (EMG) data were analyzed. The [18F]-FP-CIT brain positron emission tomography (PET) and the Unified Parkinson's Disease Rating Scale (UPDRS) were assessed for patients who showed parkinsonism. The causes of OT varied: parkinsonism (n = 5), idiopathic causes (n = 4), secondary causes (n = 3, trauma, brain lesion, arteriovenous malformation), drug reactions (n = 3, valproate, perphenazine, haloperidol), other neurological disorders (n = 5, essential tremor, dystonia, restless leg syndrome, REM sleep behavior disorder, dementia), alcohol withdrawal (n = 1), functional movement disorder (n = 1), and an unknown cause (n = 1). The frequency range varied (2.6-15 Hz) and according to the new consensus statement on the classification of OT, 4 patients had primary OT, 2 had \"primary OT plus,\" 12 had slow OT, and 5 had orthostatic myoclonus. The prognosis associated with the use of medication was generally poor; however, clonazepam and levodopa were the most effective drugs. In conclusion, we found that different types of OT and orthostatic myoclonus were diagnosed by electrophysiological evaluation and neuroimaging tools even if they showed the same symptoms as \"shaky leg.\" In addition, it is possible to roughly estimate the response to medication according to the type of OT and the cause. To clarify the pathophysiology of OT, a large number of longitudinal cohort studies and detailed neuroimaging and electrophysiological evaluations are needed.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 1","pages":"46-54"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000509411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38463208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prevalence and Management of Saliva Problems in Motor Neuron Disease: A 4-Year Analysis of the Scottish Motor Neuron Disease Register.","authors":"Iona Pearson,&nbsp;Stella A Glasmacher,&nbsp;Judith Newton,&nbsp;Emily Beswick,&nbsp;Arpan R Mehta,&nbsp;Richard Davenport,&nbsp;Siddharthan Chandran,&nbsp;Suvankar Pal","doi":"10.1159/000514615","DOIUrl":"https://doi.org/10.1159/000514615","url":null,"abstract":"<p><strong>Introduction: </strong>Saliva problems are common and distressing for people with motor neuron disease (pwMND). Despite clinical guidelines for assessment and treatment, management of saliva problems has received little research attention.</p><p><strong>Objective: </strong>We aimed to investigate the prevalence of saliva problems in pwMND, their association with clinical factors, and their management practice using a highly curated population-based register for motor neuron disease (MND) with 99% case ascertainment.</p><p><strong>Methods: </strong>We conducted an analysis of pwMND diagnosed between January 2015 and October 2019 using the Scottish MND Register (CARE-MND [Clinical, Audit, Research, and Evaluation of MND]). The association between clinical factors and saliva problems was investigated using univariate and multivariable logistic regression; results are reported as odds ratio (OR) and 95% confidence intervals. A survey of health-care professionals involved in the care of pwMND was performed to contextualize the findings.</p><p><strong>Results: </strong>939 pwMND were included. Prevalence of saliva problems was 31.3% (294). Bulbar onset (OR 9.46 [4.7, 19.2]; p < 0.001) but not age, sex, time to diagnosis, or MND subtype were independently associated with the presence of saliva problems in multivariable regression, and 52.7% (155) of those with saliva problems received pharmacological management. The most commonly used medications were hyoscine, amitriptyline, carbocisteine, glycopyrrolate, and atropine. Evidence base (8, 72.7%) and local guidelines (10, 90.9%) were cited as the most important factors influencing treatment decision by survey respondents (n = 11).</p><p><strong>Conclusion: </strong>Saliva problems are common and associated with bulbar onset MND. A substantial proportion of pwMND with saliva problems did not receive recommended treatments. Future research is required to determine the relative efficacy of individual pharmacological treatments.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 4","pages":"147-152"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514615","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38910376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutant G2019S-LRRK2 Induces Abnormalities in Arteriolar Cerebral Blood Volume in Mouse Brains: An MRI Study.","authors":"Bo Ning, Gongbo Guo, Chunming Gu, Jiadi Xu, Adnan Bibic, Xiaofei He, Hongshuai Liu, Lin Chen, Zhiliang Wei, Wenzhen Duan, Peiying Liu, Hanzhang Lu, Peter C M van Zijl, Christopher A Ross, Wanli Smith, Jun Hua","doi":"10.1159/000510387","DOIUrl":"10.1159/000510387","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is the second most common neurodegenerative disease and the most common movement disorder characterized by motor impairments resulting from midbrain dopamine neuron loss. Abnormalities in small pial arteries and arterioles, which are the primary pathways of local delivery of nutrients and oxygen in brain tissue, have been reported in many neurodegenerative diseases including PD. Mutations in LRRK2 cause genetic PD and contribute to sporadic PD. The most common PD-linked mutation LRRK2 G2019S contributes 20-47% of genetic forms of PD in Caucasian populations. The human LRRK2 G2019S transgenic mouse model displays PD-like movement impairment and was used to identify novel LRRK2 inhibitors, which provides a useful model for studying microvascular abnormalities in PD.</p><p><strong>Objectives: </strong>To investigate abnormalities in arteriolar cerebral blood volume (CBVa) in various brain regions using the inflow-based vascular-space occupancy (iVASO) MRI technique in LRRK2 mouse models of PD.</p><p><strong>Methods: </strong>Anatomical and iVASO MRI scans were performed in 5 female and 7 male nontransgenic (nTg), 3 female and 4 male wild-type (WT) LRRK2, and 5 female and 7 male G2019S-LRRK2 mice of 9 months of age. CBVa was calculated and compared in the substantia nigra (SN), olfactory cortex, and prefrontal cortex.</p><p><strong>Results: </strong>Compared to nTg mice, G2019S-LRRK2 mice showed decreased CBVa in the SN, but increased CBVa in the olfactory and prefrontal cortex in both male and female groups, whereas WT-LRRK2 mice showed no change in CBVa in the SN (male and female), the olfactory (female), and prefrontal (female) cortex, but a slight increase in CBVa in the olfactory and prefrontal cortex in the male group only.</p><p><strong>Conclusions: </strong>Alterations in the blood volume of small arteries and arterioles (CBVa) were detected in the G2019S-LRRK2 mouse model of PD. The opposite changes in CBVa in the SN and the cortex indicate that PD pathology may have differential effects in different brain regions. Our results suggest the potential value of CBVa as a marker for clinical PD studies.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 2-3","pages":"65-72"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864856/pdf/nihms-1615668.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38571891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of NLRP3 Inflammasome, Pyroptosis, and Cell Death by NIM811 in Rotenone-Exposed Cells as an in vitro Model of Parkinson's Disease.","authors":"Minghao Zhang,&nbsp;Qingping He,&nbsp;Guisheng Chen,&nbsp;P Andy Li","doi":"10.1159/000511207","DOIUrl":"https://doi.org/10.1159/000511207","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons in the substantia nigra. Recently, NLRP3 inflammasome and pyroptosis were found to be associated with PD. Cyclosporine A (CsA), an immunosuppressant, reduces neuronal death in PD. However, CsA could hardly pass through the blood-brain barrier (BBB) and high dose is associated with severe side effects and toxicity. N-methyl-4-isoleucine-cyclosporine (NIM811) is a CsA derivate that can pass through the BBB. However, little is known about its effect on PD.</p><p><strong>Objective: </strong>The objectives of this study were to explore the mechanism of rotenone-induced cell damage and to examine the protective effects of NIM811 on the neurotoxicity of a Parkinson-like in vitro model induced by rotenone.</p><p><strong>Methods: </strong>Murine hippocampal HT22 cells were cultured with the mitochondrial complex I inhibitor rotenone, a widely used pesticide that has been used for many years as a tool to induce a PD model in vitro and in vivo and proven to be reproducible. NIM811 was added to the culture media 3 h prior to the rotenone incubation. Cell viability was determined by resazurin assay, reactive oxygen species (ROS) production by dihydroethidine (DHE), and mitochondrial membrane potential by tetramethyl rhodamine methyl ester (TMRM). TUNEL and caspase-1 immunofluorescent double staining was used to detect pyroptosis. NLRP3, caspase-1, pro-caspase-1, GSDMD, and interleukin-18 (IL-18) were measured using Western blotting after 24 h of rotenone incubation. The reactivity of interleukin-1β (IL-1β) was determined by ELISA.</p><p><strong>Results: </strong>Our results demonstrated that rotenone caused more than 40% of cell death, increased ROS production, and reduced mitochondrial membrane potential, while NIM811 reversed these alterations. Immunofluorescent double staining showed that rotenone increased the percentage of caspase-1 and TUNEL double-labelled cells, an indication of pyroptosis, after 24 h of incubation. The protein expression of NLRP3, caspase-1, pro-caspase-1, GSDMD, IL-18, and IL-1β was significantly increased after 24 h of rotenone incubation. NIM811 suppressed rotenone-induced pyroptosis and downregulated the protein expression of NLRP3, caspase-1, pro-caspase-1, GSDMD, IL-1β, and IL-18.</p><p><strong>Conclusion: </strong>These results provide evidence that rotenone activates the NLRP3 inflammomere and induces pyroptosis. NIM811 protects the cell from rotenone-induced damage and inhibits NLRP3 inflammasome and pyroptosis. NIM811 might serve as a potential therapeutic drug in the treatment of PD.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 2-3","pages":"73-83"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000511207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38685540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computerized Simple Reaction Time and Balance in Nondemented Parkinson's Patients.","authors":"Aida Arroyo-Ferrer,&nbsp;Jorge Andreo,&nbsp;José A Periáñez,&nbsp;Marcos Ríos-Lago,&nbsp;Genny Lubrini,&nbsp;Jaime Herreros-Rodríguez,&nbsp;Juan García-Caldentey,&nbsp;Juan Pablo Romero","doi":"10.1159/000517437","DOIUrl":"https://doi.org/10.1159/000517437","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) patients are known to suffer from subtle cognitive and balance deficits from the early stages although they usually manifest in advanced stages. Postural instability (PI) has been correlated with slower information processing speed. Simple reaction time (SRT) tasks can be used to measure the speed of information processing. The main objective of this study was to examine the usefulness of SRT as a valid predictor of balance in PD, thus providing a simple and complementary assessment method.</p><p><strong>Methods: </strong>This cross-sectional study included 52 PD patients without dementia who were evaluated for balance using the pull test (PT) maneuver and Biodex® limits of stability (LOS). In addition, a reaction time task was used to measure processing speed. Correlation and linear regression analyses were performed.</p><p><strong>Results: </strong>The performance of SRT tasks was correlated with the evaluation of LOS% and PT, suggesting that the SRT may be a predictor of balance performance. Longer reaction time and poorer postural stability were also associated with disease duration but not with age.</p><p><strong>Conclusions: </strong>Poor performance in a simple reaction task can predict altered PI and can complement staging and evaluation in PD patients.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 5-6","pages":"193-199"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000517437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39194768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of the Auditory Pathway in Spinocerebellar Ataxia Type 7.","authors":"Laura E Ramos-Languren,&nbsp;Roberto Rodríguez-Labrada,&nbsp;Jonathan J Magaña,&nbsp;Nalia Canales-Ochoa,&nbsp;Yanetza González-Zaldivar,&nbsp;Luis Velázquez-Pérez,&nbsp;Rigoberto González-Piña","doi":"10.1159/000517213","DOIUrl":"https://doi.org/10.1159/000517213","url":null,"abstract":"<p><strong>Background: </strong>Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder caused by a mutation in the ATXN7 gene. The involvement of the brainstem auditory pathway in pathogenesis of this disease has not been systematically assessed.</p><p><strong>Aim: </strong>To determine involvement of the brainstem auditory pathway in SCA7 patients and its relationship to clinical features of the disease.</p><p><strong>Methods: </strong>In this case-control study, brainstem auditory-evoked potentials (BAEPs) were assessed in 12 SCA7 patients with clinical and molecular diagnosis, compared to 2 control groups of 16 SCA2 patients and 16 healthy controls.</p><p><strong>Results: </strong>SCA7 patients exhibited significant prolongation of I-wave and III-wave latencies, whereas SCA2 patients showed increased latencies for III and V waves and I-III interpeak interval. SCA7 patients with larger I-wave latencies exhibited larger CAG repeats, earlier onset age, and higher SARA scores, but in SCA2 cases, these were not observed.</p><p><strong>Conclusions: </strong>BAEP tests revealed functional involvement of the auditory pathway in SCA7 (mainly at) peripheral portions, which gave new insights into the disease physiopathology different from SCA2 and may unravel distinct pathoanatomical effects of polyQ expansions in the central nervous system.</p><p><strong>Significance: </strong>These findings offer important insights into the distinctive disease mechanisms in SCA7 and SCA2, which could be useful for differential diagnosis and designing specific precision medicine approaches for both conditions.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 5-6","pages":"185-192"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000517213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39172664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic Resonance Spectroscopy following Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis on the Potential to Detect Posttraumatic Neurodegeneration.","authors":"Amanda Eisele,&nbsp;MaryJane Hill-Strathy,&nbsp;Lars Michels,&nbsp;Katrin Rauen","doi":"10.1159/000508098","DOIUrl":"https://doi.org/10.1159/000508098","url":null,"abstract":"<p><strong>Introduction: </strong>Traumatic brain injury (TBI) is the most relevant external risk factor for dementia and a major global health burden. Mild TBI (mTBI) contributes to up to 90% of all TBIs, and the classification \"mild\" often misrepresents the patient's burden who suffer from neuropsychiatric long-term sequelae. Magnetic resonance spectroscopy (MRS) allows in vivo detection of compromised brain metabolism although it is not routinely used after TBI.</p><p><strong>Objective: </strong>Thus, we performed a systematic review and meta-analysis to elucidate if MRS has the potential to identify changes in brain metabolism in adult patients after a single mTBI with a negative routine brain scan (CCT and/or MRI scan) compared to aged- and sex-matched healthy controls (HC) during the acute or subacute postinjury phase (≤90 days after mTBI).</p><p><strong>Methods: </strong>A comprehensive literature search was conducted from the first edition of electronic databases until January 31, 2020. Group analyses were performed per metabolite using a random-effects model.</p><p><strong>Results: </strong>Four and 2 out of 5,417 articles met the inclusion criteria for the meta-analysis and systematic review, respectively. For the meta-analysis, 50 mTBI patients and 51 HC with a mean age of 31 and 30 years, respectively, were scanned using N-acetyl-aspartate (NAA), a marker for neuronal integrity. Glutamate (Glu), a marker for disturbed brain metabolism, choline (Cho), a marker for increased cell membrane turnover, and creatine (Cr) were used in 2 out of the 4 included articles. Regions of interests were the frontal lobe, the white matter around 1 cm above the lateral ventricles, or the whole brain. NAA was decreased in patients compared to HC with an effect size (ES) of -0.49 (95% CI -1.08 to 0.09), primarily measured in the frontal lobe. Glu was increased in the white matter in 22 mTBI patients compared to 22 HC (ES 0.79; 95% CI 0.17-1.41). Cho was decreased in 31 mTBI patients compared to 31 HC (ES -0.31; 95% CI -0.81 to 0.19). Cr was contradictory and, therefore, potentially not suitable as a reference marker after mTBI.</p><p><strong>Conclusions: </strong>MRS pinpoints changes in posttraumatic brain metabolism that correlate with cognitive dysfunction and, thus, might possibly help to detect mTBI patients at risk for unfavorable outcome or posttraumatic neurodegeneration early.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 1","pages":"2-11"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000508098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38112348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Rivastigmine on Patients with Spinocerebellar Ataxia Type 3: A Case Series of Five Patients.","authors":"Marcus Grobe-Einsler,&nbsp;Ina Rosemarie Vogt,&nbsp;Tamara Schaprian,&nbsp;Rene Hurlemann,&nbsp;Thomas Klockgether,&nbsp;Oliver Kaut","doi":"10.1159/000510057","DOIUrl":"https://doi.org/10.1159/000510057","url":null,"abstract":"<p><strong>Background: </strong>Rivastigmine is an acetylcholine esterase inhibitor which is commonly used as therapy for dementia in Alzheimer's disease and Parkinson's disease (PD). Recently, a randomized controlled trial demonstrated a positive effect of rivastigmine on gait function in nondemented PD patients. Disturbed gait is a shared hallmark of PD and ataxias.</p><p><strong>Objectives: </strong>We hypothesized that the effect of rivastigmine could be translated to spinocerebellar ataxia (SCA) improving gait function.</p><p><strong>Method: </strong>Five patients with SCA type 3 were treated with transdermal rivastigmine for 8 weeks. The patients were monitored using the Scale for the Assessment and Rating of Ataxia (SARA) and an electronic walkway system (GAITRite®).</p><p><strong>Results: </strong>Gait function was not changed by treatment, but 4 patients who continued treatment for 8 weeks showed improved coordination of extremities. The SARA sum score, which was 7.6 ± 2.2 at baseline, had dropped by 1.5 ± 1.9 after 4 weeks and by 2.1 ± 1.4 after 8 weeks.</p><p><strong>Conclusions: </strong>Contrary to our hypothesis, we observed no improvement of gait parameters as assessed by SARA and GAIT-Rite®, but coordination abilities were improved. Rivastigmine was well tolerated, but known side effects of rivastigmine, such as deterioration of asthma, may appear. Further trials in larger cohorts are needed to confirm our findings.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 2-3","pages":"104-109"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000510057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38534235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prefrontal Cortex Transcriptomic Deconvolution Implicates Monocyte Infiltration in Parkinson's Disease.","authors":"Sai Batchu","doi":"10.1159/000510218","DOIUrl":"https://doi.org/10.1159/000510218","url":null,"abstract":"<p><strong>Introduction: </strong>Although not considered a primary cause, neuroinflammation is associated with many neurodegenerative disorders, including Parkinson's disease (PD).</p><p><strong>Methods: </strong>To elucidate potential immune involvement in PD, the present study imputed immune cell abundances from bulk RNA-sequencing transcriptomic data of PD postmortem prefrontal cortices. CIBERSORTx, an RNA deconvolution algorithm that implements support vector regression, was used to measure the relative abundances of immune cells from a previously published gene expression dataset. Through this machine-learning approach, relative proportions of 22 immune cell subtypes present in the original brain tissue were estimated.</p><p><strong>Results: </strong>Prefrontal cortices from PD patients exhibited significantly higher relative abundances of monocytes compared to neuropathologically normal controls (p value = 0.0005). The relative proportions of the other 21 immune subtypes showed no significant differences between control and PD samples.</p><p><strong>Conclusion and discussion: </strong>The findings corroborate previous reports and suggest monocytes may be involved in PD pathogenesis.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 2-3","pages":"110-112"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000510218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38426969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep-Disordered Breathing in Patients with Motor Neurone Disease: One Size Does Not Fit all.","authors":"Vinod Aiyappan,&nbsp;Peter Catcheside,&nbsp;Nick Antic,&nbsp;Graham Keighley-James,&nbsp;Jeremy Mercer,&nbsp;R Doug McEvoy","doi":"10.1159/000513887","DOIUrl":"https://doi.org/10.1159/000513887","url":null,"abstract":"<p><strong>Introduction: </strong>Sleep-disordered breathing (SDB) in patients with motor neurone disease (MND) is normally attributed to hypoventilation due to muscle weakness. However, we have observed different patterns of SDB among MND patients referred for non-invasive ventilation, which do not appear to be explained by respiratory muscle weakness alone.</p><p><strong>Aim: </strong>The aim of this study was to examine the characteristics of SDB in MND.</p><p><strong>Methods: </strong>This is a retrospective analysis of sleep studies (using polysomnography [PSG]), pulmonary function tests, and arterial blood gases in MND patients referred to a tertiary sleep medicine service for clinical review. Sleep apnoeas were characterised as obstructive or central, and to further characterise the nature of SDB, hypopnoeas were classified as obstructive versus central.</p><p><strong>Results: </strong>Among 13 MND patients who had a diagnostic PSG, the mean ± SD age was 68.9 ± 9.8 years, BMI 23.0 ± 4.3 kg/m2, forced vital capacity 55.7 ± 20.9% predicted, and partial pressure of CO2 (arterial blood) 52.7 ± 12.1 mm Hg. A total of 38% of patients (5/13) showed evidence of sleep hypoventilation. The total apnoea/hypopnoea index (AHI) was (median [interquartile range]) 44.4(36.2-56.4)/h, with 92% (12/13) showing an AHI >10/h, predominantly due to obstructive events, although 8% (1/13) also showed frequent central apnoea/hypopnoeas.</p><p><strong>Conclusions: </strong>Patients with MND exhibit a wide variety of SDB. The prevalence of obstructive sleep apnoea (OSA) is surprising considering the normal BMI in most patients. A dystonic tongue and increased upper-airway collapsibility might predispose these patients to OSA. The wide variety of SDB demonstrated might have implications for ventilator settings and patients' outcomes.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"20 4","pages":"131-138"},"PeriodicalIF":3.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000513887","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25491800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}