Prognostic factors associated with disability in a cohort of neuromyelitis optica spectrum disorder and MOG-associated disease from a nationwide Portuguese registry.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) and MOG-associated disease (MOGAD) are an increasingly recognized group of demyelinating disorders of the central nervous system. Previous studies suggest that prognosis is predicted by older age at onset, number of relapses, the severity of the first attack and autoantibody status. OBJECTIVE: To study prognostic factors associated with disability progression and additional relapses in the 3-year follow-up of a national NMOSD/MOGAD cohort. RESULTS: Out of 180 of the initial Portuguese cohort, data on 82 patients was available at the end of the follow-up period (2019-2022). Two patients died. Twenty (24.4%) patients had one or more attack in this period (25 attacks in total), mostly transverse myelitis (TM) (56.0%) or optic neuritis (32.0%). MOGAD was significantly associated with a monophasic disease course (p = 0.03), with milder attacks (p = 0.01), while AQP4 + NMOSD was associated with relapses (p = 0.03). The most common treatment modalities were azathioprine (38.8%) and rituximab (18.8%). AQP4 + NMOSD more frequently required chronic immunosuppressive treatment, particularly rituximab (p = 0.01). Eighteen (22.5%) had an EDSS ≥6 at the end of the follow-up. AQP4 + NMOSD (p < 0.01) and the occurrence of transverse myelitis (TM) during disease (p = 0.04) correlated with an EDSS≥6 at the end of the follow-up period. MOGAD was significantly associated with an EDSS<6 (p < 0.01), and MOG+ cases that reached an EDSS>6 were significantly older (64.0 ± 2.8 versus 31.0 ± 17.1, p = 0.017). A bivariate logistic regression model including the serostatus and TM attacks during disease history successfully predicted 72.2% of patients that progressed to an EDSS≥6. CONCLUSION: This study highlights that myelitis predict increased disability (EDSS≥6) in NMOSD/MOGAG and AQP4 positivity is associated with increased disability.

Nursing Ethical Decision Making on Adult Physical Restraint: A Scoping Review.

OBJECTIVE: to map the existing knowledge on nursing ethical decision making in the physical restraint of hospitalised adults. (1) Background: physical restraint is a technique that conditions the free movement of the body, with risks and benefits. The prevalence of physical restraint in healthcare suffers a wide variation, considering the environment or pathology, and it raises ethical issues that hinders decision making. This article intends to analyse and discuss this problem, starting from a literature review that will provoke a grounded discussion on the ethical and legal aspects. Inclusion criteria are: studies on physical restraint (C) and ethical nursing decision making (C) in hospitalized adults (P); (2) methods: a three-step search strategy was used according to the JBI. The databases consulted were CINAHL Plus with Full Text (EBSCOhost), MEDLINE Full Text (EBSCOhost), Nursing and Allied Health Collection: Comprehensive and Cochrane Database of Systematic Reviews (by Cochrane Library, RCAAP and Google Scholar. All articles were analysed by two independent reviewers; (3) results: according to the inclusion criteria, 18 articles were included. The categories that influence ethical decision in nursing are: consequence of the decision, the context, the nature of the decision in terms of its complexity, the principles of the ethical decision in nursing, ethical issues and universal values; (4) conclusions: the findings of this review provide evidence that there is extensive knowledge regarding nursing ethical decision making in adult physical restriction, also, it is considered an ethical issue with many associated assumptions. In this article we aim to confront all these issues from a legal perspective.

Discontinuation of disease-modifying therapy in MS patients over 60 years old and its impact on relapse rate and disease progression.

BACKGROUND / AIMS: The benefit of disease-modifying therapy (DMT) is unclear for older patients with multiple sclerosis (MS), namely those who have not experienced clinical disease activity for a prolonged time. We aimed to compare baseline differences and clinical outcomes between DMT discontinuers and continuers in a cohort of MS patients older than 60 years. METHODS: Retrospective, observational study identifying MS patients aged over 60 years, stable on DMT> 24 months. Additional inclusion criteria were a previous diagnosis of relapsing MS and a minimum follow-up period of 24 months. Differences between groups (continuers/discontinuers) were assessed. For risk of relapse and of confirmed disability worsening at follow up, a time to outcome survival model was constructed using Cox proportional hazards regression, testing for possible risk predictors. RESULTS: Thirty-five patients were included (68.6% female), with a mean age at diagnosis of 42.1 ( ± 9.5) years and a median EDSS score of 3 (IQR 2) at the age of 60 years (baseline). Thirteen patients discontinued DMT after baseline, in a mean follow-up time of 77.1 months ( ± 40.2). No differences were found between DMT continuers vs discontinuers. DMT discontinuation did not predict risk to relapse (HR 0.38, 95%CI 0.04-3.80, p = 0.408) or disability worsening at follow-up (HR 0.83, 95%CI 0.31-2.22, p = 0.712). MRI gadolinium-enhancing lesions and EDSS score > 3 at baseline were found to be independent predictors of risk to relapse and disability worsening at follow-up, respectively. CONCLUSION: DMT discontinuation did not seem to influence clinical outcome, equating with the perceived limited effect of continued immunomodulation on older stable and/or progressive patients.

Trends in online search for multiple sclerosis symptoms - Is pain a hot topic?

Assessing the relative importance among different multiple sclerosis (MS) symptoms could guide the efficient allocation of health care resources. We aimed to evaluate the trends in web search behavior worldwide regarding MS symptoms, by querying Google Trends using search terms related to MS symptoms. The popularity of those symptoms was evaluated worldwide from 16/April/2017 through 3/April/2022. A comparison of all search terms revealed that "multiple sclerosis" pain displayed by far the highest relative search volume. Prompt screening and evidence-based interventions are necessary to evaluate pain and optimize quality of life in MS patients.

Late onset neuromyelitis optica spectrum disorders (LONMOSD) from a nationwide Portuguese study: Anti-AQP4 positive, anti-MOG positive and seronegative subgroups.

INTRODUCTION: Several neuroimmunological disorders have distinct phenotypes according to the age of onset, as in multiple sclerosis or myasthenia gravis. It is also described that late onset NMOSD (LONMOSD) has a different phenotype. OBJECTIVE: To describe the clinical/demographic characteristics of the LONMOSD and distinguish them from those with early onset (EONMOSD). METHODS: From a nationwide Portuguese NMOSD study we analyzed the clinical/demographic characteristics of the LONMOSD. RESULTS: From the 180 Portuguese patients 45 had disease onset after 50 years old, 80% were female. 23 had anti-AQP4 antibodies (51.1%), 13 anti-MOG antibodies (28.9%) and 9 were double seronegative (20.0%). The most common presenting phenotypes in LONMOSD were transverse myelitis (53.3%) and optic neuritis (26.7%), without difference from EONMOSD (p = 0.074). The mean EDSS for LONMOSD was 6.0 (SD=2.8), after a mean follow-up time of 4.58 (SD=4.47) years, which was significantly greater than the mean EDSS of EONMOSD (3.25, SD=1.80)(p = 0.022). Anti-AQP4 antibodies positive LONMOSD patients had increased disability compared to anti-MOG antibodies positive LONMOSD (p = 0.022). The survival analysis showed a reduced time to use a cane for LONMOSD, irrespective of serostatus (p<0.001). CONCLUSIONS: LONMOSD has increased disability and faster progression, despite no differences in the presenting clinical phenotype were seen in our cohort.

Neuromyelitis optica spectrum disorders: A nationwide Portuguese clinical epidemiological study.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits. OBJECTIVE: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics. METHODS: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included. RESULTS: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome. CONCLUSION: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries.

Willingness to be vaccinated against COVID-19: An exploratory online survey in a Portuguese cohort of multiple sclerosis patients.

BACKGROUND: Little is known about MS patients' acceptability of a COVID-19 vaccine. OBJECTIVE AND METHODS: An online survey was conducted among MS patients to study COVID-19 vaccine acceptability and its associated factors. RESULTS AND CONCLUSION: Among 256 participants, 80.9% of the patients were either definitely or probably willing to receive a COVID-19 vaccine. Most hesitant patients would consider being vaccinated under physician recommendation. Older patients and those with comorbidities seem to be more willing to get vaccinated. Moreover, vaccine acceptability was associated with participants' convictions and concerns about COVID-19, as well as previous vaccination practices.

TyPed study: Natalizumab for the treatment of pediatric-onset multiple sclerosis in Portugal.

BACKGROUND: A significant proportion of pediatric-onset multiple sclerosis (POMS) patients do not respond to first-line disease-modifying therapies. Clinical trials showed that natalizumab is effective and safe in adults, but there are limited clinical trial data for children. Natalizumab is currently prescribed off-label for POMS. We aimed to characterize the effectiveness, safety and tolerability of natalizumab in all POMS cases treated in Portugal (from 2007 to 2018). METHODS: Data from clinical records were retrospectively collected for all POMS cases treated with natalizumab in Portugal. RESULTS: Twenty-one patients were included, 14 (67%) of which were female. The median age at POMS diagnosis was 13 years old. The median duration of treatment with natalizumab was 2 years and 3 months. Median Expanded Disability Status Scale score decreased from 1.5 to 1.0 after 24 months. The Annualized Relapse Rate decreased from 1.31 events/patient/year before treatment with natalizumab to 0 after 12 months of treatment and to 0.04 after 24 months. No gadolinium-enhancing lesions or new or enlarged T2 hyperintense lesions were observed in 8/8 patients (100%) after 12 months, and 4/5 (80%) after 24 months. There was one possible serious adverse event, which did not require dose adjustment. Five patients discontinued treatment due to positive anti-JCV (JC virus) antibody JC serostatus. CONCLUSION: Natalizumab may be an effective and safe disease-modifying therapy for POMS. Our results are in line with data published for the adult population, as well as with similar observational studies in pediatric populations in other regions.

RISCOP-Cognitive profile in a Portuguese cohort of radiological isolated syndrome patients: A case-control study.

INTRODUCTION: Radiologically isolated syndrome (RIS) refers to the incidental discovery of white matter lesions suggestive of MS, on brain MRI, in asymptomatic patients. Recent studies suggest similar features of cognitive impairment between RIS and MS patients. Also, lower levels of health-related quality of life (QOL) and fatigue are reported in such patients. AIMS: characterize and compare the cognitive profile of a multicentric Portuguese cohort of RIS patients with a control group. METHODS: multicentric comparative study of a cohort of adult patients with RIS, and age and gender-matched controls followed in the headache outpatient clinic with prior MRI not fulfilling criteria for RIS diagnosis. We conducted interviews with participants, collected clinical data and applied the BICAMS battery and self-reported questionnaires (HADS, MFIS, MSQOL-54). RESULTS: we evaluated 31 patients with RIS (median age 46 years, IQR [(Dusankova et al., 2012-52], 72% women) and 19 control individuals (median age 32 years, IQR [(O'Jile et al., 2005-48], 71% women). Prevalence of cognitive impairment did not differ between groups (16% of the RIS and 10% of the controls, p=0.579). We found no differences between groups on the BICAMS tests, although the results of the California Verbal Learning Test (CVLT-II) score presented a trend to significance, with a lower value on the RIS group (53.9 vs. 59.3, p=0.066). There were no significant differences regarding fatigue, QOL, anxiety/depression scores. CONCLUSION: this is the first study on a Portuguese cohort of RIS patients assessing cognitive profile with BICAMS. A non-neglectable part of our cohort presented cognitive impairment. Our findings add to previous studies in suggesting that a more pronounced impairment of verbal memory and learning, evaluated by CVLT-II, may be present in RIS patients compared to controls. BICAMS should be assessed on future studies with larger cohorts.

Prognostic value of kappa free light chains determination in first-ever multiple sclerosis relapse.

Given its highly variable clinical course, an unmet need for objective prognostic assessment in Multiple Sclerosis (MS) persists. In this work, we suggest that CSF kappa free light chains (KFLC) determination at first relapse may provide insight into future disease activity and disability worsening. We quantified KFLC by nephelometry in paired CSF/serum samples of 28 patients, collected within one month of first-ever MS relapse, and explored correlations with clinical data on disease activity, retrospectively registered across a median follow-up time of 79 months. We documented KFLC ratio (CSF-FKLC/Serum-KFLC) as an independent predictor of second relapse occurrence and disability worsening at follow-up, in this cohort.

A multicenter, non-interventional study to evaluate the disease activity in Multiple Sclerosis after withdrawal of Natalizumab in Portugal.

OBJECTIVES: Natalizumab (NTZ) is very effective for treatment of relapsing-remitting multiple sclerosis (RRMS), its use is mainly limited by safety issues. Discontinuation of NTZ is associated with recurrence of disease activity (reactivation and rebound). The best strategy for subsequent therapy and the predictive factors for recurrence in such patients are areas of active research. We aimed to evaluate predictors of reactivation in a multicentric study. PATIENTS AND METHODS: Multicentric retrospective observational study in five portuguese MS referral centers. Demographic, clinical and imagiological data were collected in the year prior, during and in the year following NTZ discontinuation. Predictors of reactivation and rebound after NTZ suspension were studied using a multivariate Cox model. RESULTS: Sixty-nine patients were included. They were mainly non-naïve patients (97%), with a mean age of 29.1 ±â€¯8.3 years at diagnosis, and a mean age of 37.2 ±â€¯10.3 years at NTZ initiation. The mean annualized relapse rate (ARR) previous, during and after NTZ was 1.6 ±â€¯1.2, 0.2 ±â€¯0.5 and 0.6 ±â€¯1.0, respectively. The median EDSS before, during and after NTZ was 3.5 (IQR 3.3), 3.5 (IQR 3.5) and 4.0 (IQR 3.8), respectively. The median number of infusions was 26.0 (IQR 12.5) and the main reason to NTZ discontinuation was progressive multifocal leukoencephalopathy (PML) risk (70%). After NTZ suspension, reactivation was observed in 25 (36%) patients after a median time of 20.0 (IQR 29.0) weeks. Reactivation predictors in our sample included NTZ suspension for reasons other than PML (adjusted HR = 0.228, 95% CI [0.084- 0.616], p = 0.004), ARR before NTZ (adjusted HR = 1.914 95% [CI 1.330-2.754], p < 0.001) and a longer disease duration at time of NTZ initiation (adjusted HR = 1.154, 95% CI [1.020-1.306], p = 0.023). Rebound occurred in 5 (7%) patients after a median time of 20 (IQR 34.5) weeks. CONCLUSION: Significant predictors of disease reactivation in our cohort were discontinuation of NTZ for reasons other than PML risk, higher disease activity before NTZ treatment, and longer disease duration. Our study provides valuable data of portuguese patients after NTZ withdrawal.

Stem Cell-Derived Neurons as Cellular Models of Sporadic Alzheimer's Disease.

Alzheimer's disease (AD) occurs as either an autosomal dominant inherited disease or sporadically. While familial mutant genes can be expressed in cells or in animal models to assess dysregulated functions, sporadic AD cannot be replicated in models given our lack of understanding of causality. Furthermore, the study of sporadic forms of AD is difficult given the inaccessibility of brain tissues in living individuals and the manifestation of symptoms years after the onset of disease. Here, the objective was to assess if induced pluripotent stem cell-derived neurons from well-ascertained sporadic AD individuals could represent potential cellular models to determine the underlying molecular mechanisms of disease. We used cryopreserved peripheral blood mononuclear cells from three well-ascertained sporadic AD and three non-cognitively impaired (NCI) individuals of the CIMA-Q cohort to obtain iPSC-derived neurons. Microtubule associated protein 2 was decreased in AD neurons, whereas expression of AD-associated amyloid precursor protein, tau, and amyloid-ß peptide was similar in AD and NCI individuals. RNA sequencing identified several upregulated and downregulated mRNAs in AD relative to NCI neurons. Of these, complement Factor H (CFH), signal regulatory protein beta1 (SIRPB1), and insulin like growth factor binding protein 5 (IGFBP5) were previously associated with AD. In addition, several transcription factors not previously associated with AD, but involved in neuronal proliferation and differentiation were differentially expressed. The results identify novel avenues for the study of the underlying causes of sporadic AD and support the establishment of additional lines to identify mechanisms of disease in sporadic AD individuals.

Effect of patients' expectations on clinical response to fampridine treatment.

INTRODUCTION: Patient expectation of treatment outcome is one of the primary mechanisms underlying the placebo effect. In multiple sclerosis trials with symptomatic treatments, a robust placebo effect is observed, which might be related to patient expectations. The aim of this study was to evaluate whether patient expectations regarding fampridine treatment influence the clinical response after 4 weeks and 6 months of treatment. MATERIALS AND METHODS: We designed and carried out a prospective study from June 2015 to August 2017. Before treatment, patients completed a questionnaire including a scale evaluating their expectations regarding the treatment. The effect of baseline positive expectancy on the response status after 4 weeks and 6 months of treatment was analyzed through univariable and, when applicable, multivariable analysis. RESULTS: A total of 47 consecutive patients were included in the study. At week 4, 37 (78.7%) patients were classified as responders; a one-point increase in the positive expectancy questionnaire was significantly associated with a fourfold increase in the likelihood of being a responder [OR = 4.020 (95% CI 1.082-14.933); p = 0.038]. At 6 months, 43 patients completed follow-up. The number of responders decreased to 28; at this point, positive expectancy at baseline was no longer associated with response status. CONCLUSION: Baseline positive expectancy regarding fampridine was determinant of the clinical response after 4 weeks of treatment. However, in the long term, fampridine efficacy was not dependent on expectations prior to treatment.

The Influence of Menopause in Multiple Sclerosis Course: A Longitudinal Cohort Study.

BACKGROUND: Hormonal variations are known to influence the course of multiple sclerosis (MS). OBJECTIVES: We aimed to evaluate the impact of menopause in MS course, including disease activity and disability progression. METHODS: We conducted a retrospective longitudinal cohort study including all women, older than 44, post-menopausal, with a diagnosis of MS at least 1 year before menopause. We evaluated the impact of menopause in MS course comparing clinical and radiologic outcomes within 5 years before and after menopause. We repeated the analysis in subgroups of patients without disease-modifying treatment (DMT) change or co-morbidities diagnosed during the observation period, considering that those factors might also impact MS outcomes. RESULTS: Thirty-seven women, with a mean age at the time of menopause of 49.8 (±4.06) years were included in the analysis. Within 5 years following menopause, we observed a decrease in the annualized relapse rate (0.37 ± 0.35 pre-menopause vs. 0.08 ± 0.18 post-menopause, p < 0.001) compared with the same period before menopause, while the EDSS progression rate remained stable (0.13 ± 0.24 EDSS point/year pre-menopausal vs. 0.13 ± 0.18 post-menopause, p = 0.935). EDSS progression events frequency was similar before and after the menopause (37.8 vs. 48.6%, respectively, p = 0.424). These observations persisted in patients' subgroups without DMT switch or co-morbidities. CONCLUSIONS: Following menopause, we observed a reduction in the relapse rate, but the disability progression continued at a similar rate, compared to the pre-menopausal period. These observations persisted in the subgroup of patients without changes in DMT or co-morbidities diagnosed during the observation period.

Pediatric Multiple Sclerosis in Portugal: A Multicentre Study.

INTRODUCTION: Multiple sclerosis is most often diagnosed among young adults but less frequently it may present during childhood or adolescence. In Portugal, there has been only one previous single-center, pediatric multiple sclerosis study. The main objective was the evaluation of the demographic, clinical, laboratorial and neuroradiological characteristics of patients with pediatric-onset multiple sclerosis in Portugal. The secondary objectives were to compare the characteristics of childhood-onset multiple sclerosis and adolescent-onset multiple sclerosis and to characterize the treatments prescribed. MATERIAL AND METHODS: We performed a retrospective observational, multicentric study. We reviewed data of all patients with multiple sclerosis younger than 18 years at the onset of their first multiple sclerosis symptoms. RESULTS: There were 46 patients (72% female) included with a mean age at diagnosis of 16.1 years. Six cases had childhood-onset and 40 cases had adolescence-onset. The median value of Expanded Disability Status Scale was two. Relapsing-remitting multiple sclerosis was most prevalent (98% of cases). In the cerebrospinal fluid study, 74% of patients had positive oligoclonal bands. Brain magnetic resonance imaging studies showed a predominant supratentorial involvement (98% of cases), whereas the cervical segment was the most frequently affected in the spinal cord. All the patients enrolled in the study underwent immunomodulatory therapy, 75% ofpatients with beta-interferon. Concerning differences between the childhood and the adolescent groups, we found a greater proportion of male patients and of individuals with cerebrospinal fluid pleocytosis among the childhood-onset group. DISCUSSION: This study provides new data on pediatric multiple sclerosis characteristics in Portugal and our results are similar to previously reported data in other parts of the worldConclusion: This is the first multicentric study characterizing pediatric multiple sclerosis in Portugal. The mechanisms underlying the particularities of pediatric multiple sclerosis remain largely unknown and further studies are required.

Introdução: A esclerose múltipla é habitualmente diagnosticada em adultos jovens mas, mais raramente, pode manifestar-se durante a infância ou adolescência. Os dados sobre a esclerose múltipla pediátrica em Portugal são escassos. O objectivo principal deste estudo é a avaliação das características demográficas, clínicas, laboratoriais e neurorradiológicas da esclerose múltipla de início em idade pediátrica em Portugal. Os objetivos secundários consistem na comparação entre a esclerose múltipla de início na infância e a esclerose múltipla de início na adolescência e na caracterização dos tratamentos prescritos. Material e Métodos: Realizou-se um estudo retrospectivo, observacional e multicêntrico, que consistiu na análise dos dados de todos os doentes com apresentação da EM antes dos 18 anos. Resultados: Incluíram-se 46 doentes (72% do sexo feminino), com uma idade média de diagnóstico de 16,1 anos. Seis casos tiveram início na infância, 40 na adolescência. A esclerose múltipla apresentou-se em 98% dos casos com a forma surto-remissão. O estudo do líquor revelou bandas oligoclonais em 74% dos doentes. A ressonância magnética encefálica mostrou predominantemente lesões supratentoriais (98% dos casos), enquanto que a ressonância medular revelou que o segmento cervical foi o mais frequentemente afectado. Todos os doentes iniciaram terapêutica imunomoduladora (75% com interferão ß). Relativamente às diferenças entre os dois grupos etários, encontrámos uma maior proporção de doentes do sexo masculino e com pleocitose no grupo com apresentação na infância. Discussão: Este trabalho fornece novos dados sobre as características da esclerose múltipla pediátrica em Portugal e os resultados são semelhantes aos reportados em outras partes do mundo. Conclusão: Este é o primeiro estudo multicêntrico português sobre a esclerose múltipla com apresentação na infância e adolescência. Mais estudos são necessários para clarificar os mecanismos subjacentes às particularidades da esclerose múltipla pediátrica.

Inflammation Induces TDP-43 Mislocalization and Aggregation.

TAR DNA-binding protein 43 (TDP-43) is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we report that lipopolysaccharide (LPS)-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α) increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T) transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.