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The histopathological characteristic of intracranial microbial aneurysm (MA)-infectious aneurysm is the presence of infection and destruction of the walls of the vessels. It can occur in the setting of predisposing infections that spread by endovascular mechanism (e.g., infective endocarditis) or extravascular mechanism (e.g., meningitis). MA is probably a better term than mycotic, infectious, or infective aneurysm as a wide variety of bacteria, fungi, mycobacteria, and virus can cause MA. Typically MAs are multiple, distal, and fusiform aneurysms, but the angiographic and clinical presentations can vary widely. The most common presentation of MA is intracranial bleed. CT angiography, MR angiography, or Digital subtraction angiography can be deployed to detect MA. By combining the clinical findings, imaging, and angiographic findings, it is possible to arrive at a correct diagnosis in most instances. MAs carry higher risk of rupture and fatal bleed when compared to other aneurysms. The treatment options include antimicrobial therapy, surgery, and endovascular therapy. The management strategy is based on large case series rather than controlled trials. All MA should receive appropriate antibiotic therapy. Ruptured MA with mass effect would require surgery in most situations, while those without mass effect and in non-eloquent locations could also be managed by endovascular therapy. Unruptured MA could be managed according to the size, location, and risk of bleeding-by antibiotic therapy, surgery, or endovascular therapy. Monitoring the resolution of the MA under antibiotic therapy by serial CT angiography is another option, but it carries higher risk of bleeding. Treatment of the underlying predisposing infection is an important component of therapy. [ABSTRACT FROM AUTHOR]

Nosocomial infections during immunotherapy pose a dilemma in the treatment of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, where a lack of consensus guidelines for this rare disease marks a significant gap in the existing knowledge. This case reports about an 18-year-old female diagnosed with anti-NMDAR encephalitis who was found to be refractory to first- and second-line treatment. During her hospital stay, the patient encountered nearly six episodes of infection, which delayed the use of next-line intervention. It was observed that switching over to the next line of treatment during infections may produce sub-therapeutic outcomes. Thereby, the case highlights the need for de-escalation and appropriate selection of immunosuppression therapy during nosocomial infections and how monotherapy with the patient-tolerated first-line agent can be appropriate during infection.

Background: Cerebrospinal fluid (CSF) indices reflecting intrathecal antibody production and blood-brain barrier impairment are not routinely assessed in patients with autoimmune encephalitis (AE). We aimed to study CSF indices and their association with the prognosis of AE., Methods: This retrospective cohort study conducted at Amrita Institute of Medical Sciences (AIMS), Kochi, India, included 60 patients aged more than 18 years with definite/probable/possible AE admitted to the Department of Neurology from August 2016 to November 2021. We introduced a classification of treatment response based on modified Rankin Scale change over time and treatment modalities., Results: In our cohort of 60 patients (six [10%] seropositive cases), a good rapid treatment response was associated with CSF white blood cell count of more than 4 cells/mm3 (OR, 4.57; 95% CI 1.31-15.96; P = .02) and positive immunoglobulin G (IgG) Local Synthesis (OR, 7.27; 95% CI 1.56-33.86; P = .01). Albumin Index had association with a poor Glasgow Coma Scale score at the nadir of the disease (OR, 1.17; 95% CI 1.01-1.34; P = .04). Similar results were yielded in the seronegative cohort. IgG Local Synthesis appeared to be a strong predictor for good rapid treatment response in both univariate and multivariate (adjusted OR, 28.71; 95% CI 2.12-389.22; P= .01) analysis. Time to immunotherapy was reversely correlated with good response overall (in the cohort with outliers removed [N = 49]: unadjusted OR 0.97, 95% CI 0.95-0.99; P= .01; adjusted OR 0.97; 95% CI 0.95-0.99; P= .008)., Conclusion: CSF indices reflecting intrathecal antibody production and blood-brain barrier impairment appear to be promising predictors of disease severity and therapeutic response in patients with autoimmune encephalitis., Competing Interests: Declaration of Competing Interest none. The preliminary results of this study were presented at the American Academy of Neurology Summer Conference-2022; July 17, 2022, San Francisco, California. DOI: 10.1212/01.wnl.0000903388.67855.1f. The abstract with the final results of the study has been accepted to the 148th Annual Meeting of the American Neurological Association, Philadelphia, September 9–12, 2023. Study data (study protocol, statistical analysis plan, data tables) can be shared on request., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Multidrug resistance has become a global health problem associated with high morbidity and mortality. Antimicrobial peptides have been acknowledged as potential leads for prospective anti-infectives. Owing to their scavenging lifestyle, Corvus splendens is thought to have developed robust immunity to pathogens found in their diet, implying that they have evolved mechanisms to resist infection. In the current study, the transcriptome of C. splendens was sequenced, and de novo assembled to identify the presence of antimicrobial peptide genes. 72.09 million high-quality clean reads were obtained which were then de novo assembled into 3,43,503 transcripts and 74,958 unigenes. About 37,559 unigenes were successfully annotated using SwissProt, Pfam, GO, and KEGG databases. A search against APD3, CAMP R3 and LAMP databases identified 63 AMP candidates belonging to more than 20 diverse families and functional classes. mRNA of AvBD-2, AvBD-13 and CATH-2 were found to be differentially expressed between the three tested crows as well as among the tissues. We also characterized Corvus Cathelicidin 2 (CATH-2) to gain knowledge of its antimicrobial mechanisms. The CD spectroscopy of synthesized mature Corvus CATH-2 peptide displayed an amphipathic α-helical structure. Though the synthetic CATH-2 caused hemolysis of human RBC, it also exhibited antimicrobial activity against E. coli, S. aureus, and B. cereus. Docking simulation results revealed that this peptide could bind to the LPS binding site of MD-2, which may prevent LPS from entering the MD-2 binding pocket, and trigger TLR4 signaling pathway. The Corvus CATH-2 characterized in this study could aid in the development of novel therapeutics., (© 2023. The Author(s).)

Objective: To study the neurological manifestations of glutamic acid decarboxylase (GAD 65) autoimmunity in Indian patients., Methods: Retrospective study conducted in a tertiary care referral hospital in South India. Patients who tested positive for GAD 65 antibodies from February 2013 to July 2019 were included., Results: We identified 922 patients who underwent GAD 65 testing, of which 81 tested positive (8.78%) [mean age 55.42 years (SD 17.39, range 9-86 years, median age 57 years)]. Males ( n = 47) outnumbered the females ( n = 34). All the GAD values measured were <5000 IU/ml. There were 34 cases (42%) of atypical parkinsonism (16/34, 47% fulfilled the diagnostic criteria for autoimmune atypical parkinsonism) in our series forming the most common group with GAD 65 positivity, followed by autoimmune encephalitis (8 cases, 9.88%). Men were more affected with atypical parkinsonism (22/34; 64.70%), stiff person syndrome (2/3; 66.66%), and neuropathy (4/7; 57.1%) while women were more with autoimmune encephalitis (6/8; 75%). Eighteen (22.6%) had underlying autoimmunity (three had type 1 diabetes mellitus). Six (7.4%) had underlying neoplasm. Thirty-three out of 43 patients responded to immunotherapy (76.74%). Five had spontaneous improvement., Conclusion: Glutamic acid decarboxylase65 antibody values were much lower in our study population. Male-dominant autoimmunity was seen unlike that in Western literature. The most striking was the high preponderance of atypical parkinsonism in GAD 65-positive patients. We also found that GAD 65 positivity is a useful marker for a positive response to immunotherapy in suspected autoimmune neurological syndromes irrespective of their titers., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Indian Academy of Neurology.)

Background: Research suggests demographic, economic, residential, and health-related factors influence vulnerability to environmental exposures. Greater environmental vulnerability may exacerbate environmentally related health outcomes. We developed a neighborhood environmental vulnerability index (NEVI) to operationalize environmental vulnerability on a neighborhood level., Objective: We explored the relationship between NEVI and pediatric asthma emergency department (ED) visits (2014-19) in 3 US metropolitan areas: Los Angeles County, Calif; Fulton County, Ga; and New York City, NY., Methods: We performed separate linear regression analyses examining the association between overall NEVI score and domain-specific NEVI scores (demographic, economic, residential, health status) with pediatric asthma ED visits (per 10,000) across each area., Results: Linear regression analyses suggest that higher overall and domain-specific NEVI scores were associated with higher annual pediatric asthma ED visits. Adjusted R 2 values suggest that overall NEVI scores explained at least 40% of the variance in pediatric asthma ED visits. Overall NEVI scores explained more of the variance in pediatric asthma ED visits in Fulton County. NEVI scores for the demographic, economic, and health status domains explained more of the variance in pediatric asthma ED visits in each area compared to the NEVI score for the residential domain., Conclusion: Greater neighborhood environmental vulnerability was associated with greater pediatric asthma ED visits in each area. The relationship differed in effect size and variance explained across the areas. Future studies can use NEVI to identify populations in need of greater resources to mitigate the severity of environmentally related outcomes, such as pediatric asthma., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Neuromyelitis Optica Spectrum Disorders (NMOSD) is an autoimmune syndrome that is frequently positive for Aquaporin 4 (AQP4) IgG or Myelin Oligodendrocyte Glycoproteins (MOG) IgG. However, dual positivity to both is rare., Objective: To assess the prevalence of dual-positive NMOSD and outline its clinical phenotype., Design/methods: This is a retrospective cross-sectional study conducted at a tertiary healthcare center in South Asia between August 2018 and November 2021. The serum and/or CSF samples of suspected cases of NMOSD were tested for both AQP4-IgG and MOG-IgG using an Indirect immunofluorescence test on transfected cells., Results: During the study period, 1935 cases of NMOSD were tested for both antibodies- 65 patients (3.35%; 57 females and 8 males) tested positive for AQP4-IgG, 217 patients (11.21%; 122 females and 95 males) tested positive for MOG-IgG and 3 patients (0.15%; 2 females and 1 male) showed dual positivity. There was a strong female preponderance in all three groups (87.69%, 56.22%, and 66.66% respectively). This study identified 3 patients with dual positivity. The first patient (42 years, Male) presented with area postrema syndrome initially and subsequently relapsed by developing right-sided numbness of the temporal area and limbs during which he tested dual positive. The second patient (27 years, Female) presented with bilateral optic neuritis (left>right) initially and subsequently relapsed following an episode of a seizure with left-sided hemiplegia. The third patient (25 years, Female) initially presented with acute bilateral optic neuritis and later developed left-sided hemiplegia post-recovery at which point she tested dual positive. Management using methylprednisolone was ineffective for all three patients, however, plasmapheresis and/or periodic rituximab injections produced an excellent response., Conclusions: Our study reports that the prevalence of dual-positive NMOSD is 0.15% and its clinical phenotype is more similar to NMO rather than MOG- associated disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Background: CSF free light chains help diagnose multiple sclerosis, but no data is available on the Asian population. Our objective was to study the diagnostic utility of CSF free light chains for diagnosing multiple sclerosis in Indian patients., Methods: Prospective multicentric case-control study. Cases included those who were tested for oligoclonal bands and fulfilled the modified McDonald criteria 2017 for multiple sclerosis and clinically isolated syndromes. Those tested for oligoclonal bands (OCB) but with other diagnoses- inflammatory and non-inflammatory were included as controls. Clinical details were collected from electronic medical records. CSF and serum kappa and lambda free light chains were measured, apart from oligoclonal bands, immunoglobulin, and albumin in paired serum and CSF samples., Results: There were 70 patients (31 cases and 39 controls). The mean age was 43.41(SD 16.073) years, and 43(61.4%) were females. CSF kappa showed highest specificity 97.4%, at a cut off 2.06 mg/L (sensitivity 71%) and highest sensitivity 90.3%, at a cut off 0.47 mg/L (specificity 79.5%). Best balance of sensitivity and specificity for CSF kappa was seen at a cut-off of ≥ 0.63 mg/L {sensitivity 87·1 (CI - 70.17-96.37), and specificity 87·18 (CI -72.57-95.70)}. The ratio of Kappa/lambda showed highest specificity of 100%(similar to OCB) with a sensitivity of 71% at a cut off of 1.72. The ratio of sum of kappa and lambda light chains, and Qalb (∑CSF FLC/Qalb), showed the highest specificity (94.87%)among the blood brain barrier corrected ratios., Conclusion: This study showed that the diagnostic utility of CSF kappa was comparable to OCB to diagnose multiple sclerosis in sensitivity, but not specificity, so can be a screening test before testing for OCB in our population., Competing Interests: Declaration of Competing Interest None of the authors report any conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

With the advancement of technology in image capturing, people are accustomed to high-resolution images. One of the primary necessities of an image capturing system is to provide the same. However, in many cases, the image resolution may not be reaching the expectations of the user which leads to a decrease in user experience. This is a common phenomenon that occurs when the images are captured in low light or if the image encounters a distortion either because of lack of exposure or the image capturing devices may be equipped with a small size sensor. In this work, a resolution enhancement technique using the concepts of curvelet transform and iterative back projection is presented. Sparse representation of images can be enhanced using a combination of curvelet transforms with iterative back projection. Application of curvelet transform along with iterative back projection algorithm on low light images results in enhancing the resolution of the images. The resultant images from here then passed through the inverse transform block and gives an image with contrast enhancement which leads to the user experience improvement. The antiquated image enhancement with improvement in the resolution is validated with the measurement of peak signal-to-noise ratio and structural similarity index. The usage of curvelet transform with iterative back projection leads to the restoration of the image resolution by minimizing the distortions, thus leading to an enhanced image whose edge details are retained., (© 2023. The Author(s).)

In the emerging context of gut-brain control of multiple sclerosis (MS), developing therapeutics targeting proinflammatory proteins controlling the gut-brain immunomodulation is welcoming. One such immunomodulator is glia maturation factor-β (GMF-β). GMF-β activation following GMF-β-ser-83 phosphorylation upregulates proinflammatory responses and exacerbates experimental autoimmune encephalomyelitis (EAE). Notably, GMF-β -/- mice exhibited no EAE symptoms. Thus, we identified 1 H -indazole-4-yl-methanol (GMFBI.1) inhibitor which blocked GMF-β-ser-83 phosphorylation critical in EAE suppression. To establish gut GMF-β's role in EAE in the context of gut-brain involvement in neurodegenerative diseases, we altered gut GMFBI.1 bioavailability as an index of EAE suppression. At first, we identified Miglyol 812N as a suitable biocompatible GMFBI.1 carrier compared to other FDA-approved carriers using in silico molecular docking analysis. GMFBI.1 administration in Miglyol 812N enhanced its retention/brain permeability. Subsequently, we administered GMFBI.1-Miglyol 812N by subcutaneous/oral routes at different doses with differential GMFBI.1 bioavailability in gut and brain to assess the role of local GMFBI.1 bioavailability in EAE reversal by a pharmacokinetic approach. Deprival of gut GMFBI.1 bioavailability led to partial EAE suppression despite having sufficient GMFBI.1 in circulation to inhibit brain GMF-β activity. Restoration of gut GMFBI.1 bioavailability led to complete EAE reversal. Molecular pathology behind partial/full EAE reversal was associated with differential GMF-β-Ser-83 phosphorylation/GM-CSF expression levels in enteric glial cells owing to GMFBI.1 bioavailability. In addition, we observed leaky gut reversal, tight junction protein ZO-1 restoration, beneficial gut microbiome repopulation, recovery from gut dysbiosis, and upregulation of Treg cells. GMFBI.1's dual gut/brain targeting of GMF-β has therapeutical/translational potential in controlling autoimmunity in MS.

Extrapyramidal symptoms are seen in patients with leucine-rich glioma-inactivated 1 (LGI1) antibody-positive patients infrequently and this can be successfully treated with immunotherapy. This is a retrospective hospital-based study from 2013 to 2021 at a tertiary care referral hospital in South India. LGI1 antibody-positive cases with Faciobrachio-crural dystonic seizures [FBCDS] were identified by reviewing electronic medical records and Neuroimmunology laboratory register. Clinical and laboratory details and treatment outcomes were analysed. There was a total of 23 patients who were positive for LGI1 antibody. Of these, three cases had FBCDS (2 males, age range 30-76 years). Upon reviewing the records they had additional asymmetric parkinsonian features. All had similar presentations with progressive slowness of activities and gait and later went on to have paroxysmal events of sudden falls with vocalization. Prolonged VEEG monitoring captured the habitual event, which were confirmed to be FBCDS. MRI did not show significant structural abnormalities, CSF showed elevated proteins and normal cell in two and lymphocytic pleocytosis in one, PET scans ruled out malignancy. Of the three patients, two were completely relieved of FBCDS with immunosuppression and there was complete resolution of extrapyramidal features in all. Thus, the patients in our series of FBCDS showed additional features of parkinsonism which responded well to immunotherapy. Involvement of basal ganglia can explain all the manifestations of this phenotype. This series reveals a unique phenotype of the LGI1 antibody., (© 2022. The Author(s) under exclusive licence to Belgian Neurological Society.)

Competing Interests: There are no conflicts of interest.

Background: The COVID-19 pandemic has overrun hospital systems while exacerbating economic hardship and food insecurity on a global scale. In an effort to understand how early action to find and control the virus is associated with cumulative outcomes, we explored how country-level testing capacity affects later COVID-19 mortality., Methods: We used the Our World in Data database to explore testing and mortality records in 27 countries from December 31, 2019, to September 30, 2020; we applied Cox proportional hazards regression to determine the relationship between early COVID-19 testing capacity (cumulative tests per case) and later COVID-19 mortality (time to specified mortality thresholds), adjusting for country-level confounders, including median age, GDP, hospital bed capacity, population density, and nonpharmaceutical interventions., Results: Higher early testing implementation, as indicated by more cumulative tests per case when mortality was still low, was associated with a lower risk for higher per capita deaths. A sample finding indicated that a higher cumulative number of tests administered per case at the time of six deaths per million persons was associated with a lower risk of reaching 15 deaths per million persons, after adjustment for all confounders (HR = 0.909; P = 0.0001)., Conclusions: Countries that developed stronger COVID-19 testing capacity at early timepoints, as measured by tests administered per case identified, experienced a slower increase of deaths per capita. Thus, this study operationalizes the value of testing and provides empirical evidence that stronger testing capacity at early timepoints is associated with reduced mortality and improved pandemic control., (© 2021 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Importance: Few studies have addressed the combined effects of health-promoting and self-care behaviors among older adults. Thus, new research is needed to assess the potential for behavior change to prolong independence in later life. Objectives: To determine the relationships between self-care behaviors and risks of mobility and activities of daily living (ADLs) over time. Design: Longitudinal data was used from the National Health and Aging Trends Study (NHATS) cohort. Eight baseline self-care behaviors were summarized using latent class analysis. Separately, longitudinal latent classes of mobility and ADLs were created. Setting: Annual in-person interviews conducted for a nationally representative sample. Participants: The baseline study sample included 7,609 Medicare beneficiaries aged ≥65 from NHATS who were living in community or residential care settings, with a 71% response rate. The average age was 75, with 57% female, 81% white and 78% high school graduates or higher. Approximately, 80% (n = 6,064) completed 5 years of follow-up. Exposures: Favorable vs. unfavorable self-care latent classes measured at baseline. Main outcomes and Measures: Associations were measured between baseline classes and longitudinal classes of mobility and ADLs difficulty. Among decedents, 5-year associations were measured between baseline classes and years of overall, healthy, able, and healthy/able life. Results: Two habitual baseline self-care behavioral patterns (46% favorable; 54% unfavorable) and three trajectories of change in mobility and ADLs disability (maintaining independence; shifting to accommodation/difficulty; shifting to assistance) emerged over time. Participants with a favorable baseline pattern had 92% (0.90-0.94) reduced risk in shifting to assistance class and 70% (0.64-0.76) reduced risk for shifting to accommodation/difficulty class for mobility disability. Participants with a favorable baseline pattern had 86% (0.83-0.89) reduced risk in shifting to assistance class and 24% (0.11-0.36) reduced risk in shifting to accommodation/difficulty class for ADLs disability. Those with an unfavorable pattern had 2.54 times greater risk of mortality by the end of the 5-year follow-up compared to those with a favorable pattern. Conclusion: Self-care behaviors in older age represent a habitual pattern. A favorable self-care behavioral pattern decreased the risk of moving towards a more disabled profile and added years of life. Interventions should encourage self-care behaviors constituting a favorable pattern., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mielenz, Kannoth and Xue.)

There is an integral research gap regarding whether there is a relationship between pain levels and low physical activity among older women. This is a secondary analysis of a longitudinal cohort study, the Women's Health and Aging Study (WHAS) II. Our analyses included 436 community-dwelling women between the ages of 70 and 79, who were followed for 10.5 years. We employed marginal structural modeling, which controls for time-dependent confounding, with the aim of assessing the potential direct association between pain levels and low physical activity and assess a graded relationship. Compared to women with no pain, those with widespread pain were nearly half as likely to be moderately active versus low active (aOR: 0.46, 95% confidence interval (CI): 0.22, 0.96). A graded association was observed across the four pain levels (no pain or mild pain, other pain, moderate or severe lower extremity pain, and widespread pain) on low physical activity. Our findings indicate that reducing chronic widespread pain in older women may increase moderate physical activity, and therefore reduce the downstream health risks of low physical activity, including morbidity and mortality risk.

Introduction: Fall fatality rates among U.S. older adults increased 30% from 2007 to 2016. In response, the Centers for Disease Control and Prevention developed the Stopping Elderly Accidents, Deaths, and Injuries algorithm for fall risk screening, assessment, and intervention. The current Stopping Elderly Accidents, Deaths, and Injuries algorithm with 2 levels (at risk and not at risk) was adapted to an existing cohort of older adult drivers., Methods: A U.S. multisite prospective cohort (N=2,990) of drivers (aged 65-79 years), from 2015 to 2017, was used for these analyses completed in January 2020-October 2020. To measure the adapted Stopping Elderly Accidents, Deaths, and Injuries key questions for fall risk screening performance in predicting future falls, adjusted logistic regression determined the area of the receiver operating characteristic curve. An adjusted mixed logistic regression modeled the association between the adapted Stopping Elderly Accidents, Deaths, and Injuries key questions and future falls., Results: The adapted Stopping Elderly Accidents, Deaths, and Injuries key questions yielded an area under the curve of 0.65 in determining any fall over 2 years. The adjusted mixed logistic regression model suggests that those at risk for falls at baseline were associated with 2.37 times higher odds of any fall (95% CI=2.00, 2.80) and 3.60 times higher odds of multiple falls (95% CI=2.88, 4.51) over 2 years., Conclusions: The adapted Stopping Elderly Accidents, Deaths, and Injuries key questions for fall risk screening yielded fair predictive ability for falls over 2 years and were strongly associated with future falls for older adult drivers. The adapted Stopping Elderly Accidents, Deaths, and Injuries key questions can be applied to existing data in nonclinical settings to strengthen fall screening and prevention at a population level., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

A marked prozone effect was observed in indirect immunofluorescence with human sera and human cerebrospinal fluid in two clinical cases involving breast carcinoma with paraneoplastic neuronal antibodies, and anti- N-methyl-D-aspartic acid (NMDA) receptor antibodies. Anti-Yo antibodies and anti-NMDA antibodies were not detectable under high concentrations (1:10 serum dilution and neat CSF respectively) but showed a true effect when sufficiently diluted at 1:80 and 1:5 respectively. This paper demonstrates that prozone effects have their occurrences in indirect immunofluorescence, and clinicians and laboratory technicians should be wary of its implications during screening of autoantibody markers in neurological diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Anti-N-methyl-d-aspartate receptor (Anti-NMDAR) Encephalitis classically presents with polysymptomatic presentation of behavioral or cognitive changes, seizures, and focal deficits. Large series in adults and children have described the above features. Monosymptomatic presentation of Anti NMDAR encephalitis is rare and in literature single case reports in adults and children are available. Here we report a series of 6 children presenting with seizure alone and thus expanding the clinical spectrum of Anti NMDAR encephalitis., Materials and Methods: This is a a retrospective case series of 6 cases of anti NMDAR encephalitis treated in our institute, which is a tertiary referral center between 2010 and 2014. All the patients with NMDA encephalitis were initially included. The baseline demographics, clinical presentations, investigations (CSF, MRI and EEG), course in the hospital, details of treatment, short and long term outcomes were documented from the available medical records. Children presenting with monosymptomatic seizure clusters were only included in the final analysis., Results: Twenty eight children were diagnosed with ant NMDA R encephalitis during the study period. 22 children had classical polysymptomatic presentations and were not included in this analysis. The remaining 6 children (5 girls and one boy), who presented with only acute seizure clusters were included in the study. All children presented with acute cluster of focal seizures. Four out of six had focal status epilepticus while 2 out of six had recurrent focal seizures. Commonest semiology was clonic seizure in 4/6 and one child had dystonic seizure and one had tonic seizure. All patients were started on steroids and antiepileptic drugs. No other immunomodulators or immunosuppressants were used. On discharge all patients where seizure free and with no focal deficits., Conclusion: This is the first series of Anti NMDAR encephalitis presenting as new onset seizure clusters in children. Unlike the existing literature, these children did not develop any other symptoms. We propose that focal encephalitis could be the reason for this monosymptomatic presentation., Competing Interests: None

Background and Objectives: Falls account for the highest proportion of preventable injury among older adults. Thus, the United States' Centers for Disease Control and Prevention (CDC) developed the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) algorithm to screen for fall risk. We referred to our STEADI algorithm adaptation as "Quick-STEADI" and compared the predictive abilities of the three-level (low, moderate, and high risk) and two-level (at-risk and not at-risk) Quick-STEADI algorithms. We additionally assessed the qualitative implementation of the Quick-STEADI algorithm in clinical settings. Research Design and Methods: We followed a prospective cohort ( N = 200) of adults (65+ years) in the Bassett Healthcare Network (Cooperstown, NY) for 6 months in 2019. We conducted a generalized linear mixed model, adjusting for sociodemographic variables, to determine how baseline fall risk predicted subsequent daily falls. We plotted receiver operating characteristic (ROC) curves and measured the area under the curve (AUC) to determine the predictive ability of the Quick-STEADI algorithm. We identified a participant sample ( N = 8) to gauge the experience of the screening process and a screener sample ( N = 3) to evaluate the screening implementation. Results: For the three-level Quick-STEADI algorithm, participants at low and moderate risk for falls had a reduced likelihood of daily falls compared to those at high risk (-1.09, p = 0.04; -0.99, p = 0.04). For the two-level Quick-STEADI algorithm, participants not at risk for falls were not associated with a reduced likelihood of daily falls compared to those at risk (-0.89, p = 0.13). The discriminatory ability of the three-level and two-level Quick-STEADI algorithm demonstrated similar predictability of daily falls, based on AUC (0.653; 0.6570). Furthermore, participants and screeners found the Quick-STEADI algorithm to be efficient and viable. Discussion and Implications: The Quick-STEADI is a suitable, alternative fall risk screening algorithm. Qualitative assessments of the Quick-STEADI algorithm demonstrated feasibility in integrating a falls screening program in a clinical setting. Future research should address the validation and the implementation of the Quick-STEADI algorithm in community health settings to determine if falls screening and prevention can be streamlined in these settings. This may increase engagement in fall prevention programs and decrease overall fall risk among older adults., (Copyright © 2020 Mielenz, Kannoth, Jia, Pullyblank, Sorensen, Estabrooks, Stevens and Strogatz.)

The US older adult population is projected to considerably increase in the future, and continued driving mobility is important for health aspects in populations with fewer transportation alternatives. This study evaluated whether frailty is associated with low-mileage driving (<1865 miles per year) and driving cessation among older adults. Baseline demographics and health data were collected for 2990 older drivers via in-person assessments and questionnaires, with 2964 reporting baseline frailty data. Multivariable log-binomial regression models were used to evaluate the association between baseline frailty status and low-mileage driving. Multivariable Cox proportional hazards regression were used to evaluate the association between baseline frailty status and driving cessation. For every unit increase in frailty, the estimated adjusted risk of driving fewer than 1865 miles/year increased by 138% (adjusted risk ratio: 2.38, 95% CI: 1.63-3.46). Relative to older drivers who were not frail, the adjusted hazard ratios of driving cessation were 4.15 (95% CI: 1.89-9.10) for those classified as prefrail and 6.08 (95% CI: 1.36-27.26) for those classified as frail. Frailty is positively associated with low-mileage driving status and driving cessation in a dose-response fashion. Public health interventions that reduce frailty, such as physical activity, may help older drivers maintain safe and independent mobility.

Background and Objectives: The persistent status of ageism as one of the least acknowledged forms of prejudice may be due in part to an absence of quantifying its costs in economic terms. In this study, we calculated the costs of ageism on health conditions for all persons aged 60 years or older in the United States during 1 year., Research Design and Materials: The ageism predictors were discrimination aimed at older persons, negative age stereotypes, and negative self-perceptions of aging. Health care costs of ageism were computed by combining analyses of the impact of the predictors with comprehensive health care spending data in 1 year for the eight most-expensive health conditions, among all Americans aged 60 years or older. As a secondary analysis, we computed the number of these health conditions experienced due to ageism., Results: It was found that the 1-year cost of ageism was $63 billion, or one of every seven dollars spent on the 8 health conditions (15.4%), after adjusting for age and sex as well as removing overlapping costs from the three predictors. Also according to our model, ageism resulted in 17.04 million cases of these health conditions., Discussion and Implications: This is the first study to identify the economic cost that ageism imposes on health. The findings suggest that a reduction of ageism would not only have a monetary benefit for society, but also have a health benefit for older persons., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objective: Although there is anecdotal evidence of ageism occurring at both the structural level (in which societal institutions reinforce systematic bias against older persons) and individual level (in which older persons take in the negative views of aging of their culture), previous systematic reviews have not examined how both levels simultaneously influence health. Thus, the impact of ageism may be underestimated. We hypothesized that a comprehensive systematic review would reveal that these ageism levels adversely impact the health of older persons across geography, health outcomes, and time., Method: A literature search was performed using 14 databases with no restrictions on region, language, and publication type. The systematic search yielded 13,691 papers for screening, 638 for full review, and 422 studies for analyses. Sensitivity analyses that adjusted for sample size and study quality were conducted using standardized tools. The study protocol is registered (PROSPERO CRD42018090857)., Results: Ageism led to significantly worse health outcomes in 95.5% of the studies and 74.0% of the 1,159 ageism-health associations examined. The studies reported ageism effects in all 45 countries, 11 health domains, and 25 years studied, with the prevalence of significant findings increasing over time (p < .0001). A greater prevalence of significant ageism-health findings was found in less-developed countries than more-developed countries (p = .0002). Older persons who were less educated were particularly likely to experience adverse health effects of ageism. Evidence of ageism was found across the age, sex, and race/ethnicity of the targeters (i.e., persons perpetrating ageism)., Conclusion: The current analysis which included over 7 million participants is the most comprehensive review of health consequences of ageism to date. Considering that the analysis revealed that the detrimental impact of ageism on older persons' health has been occurring simultaneously at the structural and individual level in five continents, our systematic review demonstrates the pernicious reach of ageism., Competing Interests: The authors have declared that no competing interests exist.

Patient safety and quality of care are at risk if the informed consent process does not emphasize patient comprehension. In this paper, we describe how we designed, developed, and evaluated an mHealth tool for advancing the informed consent process. Our tool enables the informed consent process to be performed on tablets (e.g., iPads) utilizing virtual coaching with text-to-speech automated translation as well as an interactive multimedia elements (e.g., graphics, video clips, animations, presentations, etc.). We designed our tool to enhance patient comprehension and quality of care, while improving the efficiency of obtaining patient consent. We present the Used-Centered Design approach we adopted to develop the tool and the results of the different methods we used during the development of the tool. Also, we describe the results of the usability study which we conducted to evaluate the effectiveness, efficiency, and user satisfaction with our mHealth App to enhance the informed consent process. Using the UCD approach we were able to design, develop, and evaluate a highly interactive mHealth App to deliver the informed consent process.

Contactin-associated protein 2 (CASPR2) antibodies are originally associated with Morvan's syndrome and peripheral nerve hyper excitability. Our objective was to study retrospectively the clinical spectrum of CASPR2 antibody-positive patients in our hospital. This is a retrospective observational study. Patients treated at the Amrita Institute of Medical Sciences from May 2013 to April 2016, who were tested positive for CASPR2 antibodies, were included. A total of 1584 samples were tested in the neuroimmunology laboratory during the study period for voltage-gated potassium channel (VGKC) complex antibodies-leucine-rich glioma-inactivated protein 1 (LGI1) and CASPR2 antibodies. Thirty-four were positive for LGI1, 13 were positive for CASPR2, and 7 were for both (total 54-3.4% positivity). Of these 54 cases, 11 were treated in our hospital. Seven were positive for LGI1, three for CASPR2, and one for both. The patient who had both CASPR2 and LGI1 antibody positive had Morvan's syndrome. One patient with CASPR2 had neuromyotonia. The other patient was admitted with status epilepticus with a syndrome of parkinsonism and ataxia. The third patient had encephalopathy and myoclonus with a syndrome of parkinsonism and ataxia. Two of them underwent siddha treatment for other ailments prior to the onset of the disease for other ailments. Our short series shows the expanding spectrum of CASPR2 autoimmunity. Syndrome of parkinsonism and ataxia is an important manifestation of CASPR2 autoimmunity where we can offer a definitive treatment.

New-onset refractory focal epilepsy poses significant challenges to the clinician in the absence of specific diagnostic biomarkers. Differential diagnoses based on imaging may be expanded by a veritable spectrum of peri-ictal imaging findings that may mask the underlying substrate. We report a 13-year-old girl who presented with refractory focal seizures of left parieto-occipital origin with cytotoxic gyral oedema noted over the same region on imaging. Despite an initial negative autoantibody profile, the patient was treated with immunosuppression, followed by serial relapses requiring immune-modulation. Over the next year, her syndrome persisted as focal left posterior cortex epilepsy that necessitated occipital lobectomy, following a relapsing-remitting radiological profile, consistent with peri-ictal MRI changes. Histopathology was inconclusive for any definitive substrate. After a period of quiescence, she developed focal motor seizures of right hemispheric origin with progressive encephalopathy, at which point a repeat cerebrospinal fluid anti-N-methyl-D-aspartate receptor antibody profile returned positive. The patient was managed with steroids and rituximab with a good clinical outcome. We hypothesise that persistent or relapsing-remitting focal gyral oedema in unexplained refractory focal epilepsy mandates consideration of focal encephalitis secondary to autoimmunity, and late appearance of intrathecal auto-antibody synthesis correlates with evolution into a more diffuse disease.

This video-illustrated case report concerns a 49-year-old woman who presented with sleep-related hypermotor seizures. The antecedent history of leptospirosis, high frequency of new-onset seizures, presence of an unclassified anti-neuronal antibody, and dramatic response to steroids strongly supported post-infectious immune-mediated pathogenesis in our patient. To the best of our knowledge, post-leptospirosis autoimmune epilepsy presenting as sleep-related hypermotor seizures has not hitherto been reported. [Published with video sequence on www.epilepticdisorders.com].

Introduction: Orthostatic hypotension is defined as a sustained decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within three minutes of standing compared with blood pressure from the sitting or supine position or by head-up tilt-table testing (1). When sustained blood pressure (BP) drop is after three minutes of upright posture it is called delayed orthostatic hypotension (delayed OH) (2)., Aim of the Study: To detect the incidence of delayed orthostatic hypotension in patients referred to our autonomic lab., Materials and Method: BP was measured noninvasively at 1-minute intervals with an automated cuff sphygmomanometer over the right brachial artery for 45 minutes. The onset and duration of falls in blood pressure either systolic or diastolic or both were documented, and any associated symptoms were recorded. Only patients with sustained falls in BP were included. Drugs causing OH was stopped 48 hours before testing as per protocol followed in lab. We also looked into other autonomic function test abnormalities in patients with delayed OH., Inclusion Criteria: Patients above age of 18 years referred for evaluation of autonomic function tests., Exclusion Criteria: Patients with severe cardiac failure and cardiac arrhythmias were excluded and patients with rapid fall in BP and bradycardia (Neurally mediated syncope) were excluded., Results: Total 170 patients underwent tilt table testing. Orthostatic hypotension was seen within 3 minutes in seventy patients, fifty patients had delayed OH (BP fall after 3 minutes). There were twenty seven males and twenty three females in this group. Twenty nine of the 50 patients with delayed orthostatic hypotension, had symptoms during the tilt table procedure. Asymptomatic OH was more common in patients who developed OH after 10 minutes., Conclusion: This is a pilot study, first in India where we looked into the incidence of delayed orthostatic hypotension in patients undergoing tilt table testing in our autonomic lab. We found that fifty patients had delayed orthostatic hypotension which could have been missed on clinical evaluation. High clinical suspicion is needed to detect this disorder and tilt table testing should be done in suspicious cases since orthostatic hypotension is cause of high morbidity., Competing Interests: There are no conflicts of interest.

Background and Purpose: Cervical internal carotid artery occlusion can present with varied clinical manifestations such as transient ischemic attack, stroke, and chronic ocular ischemia, or can be asymptomatic. The outcome in these patients is considerably influenced by cerebral hemodynamic compensatory adaptation of the intracranial collateral pathways. Our aim was to study whether collateral circulation as assessed by CT angiography can predict 3-month outcome and initial stroke severity in patients with symptomatic cervical ICA occlusion., Materials and Methods: This was a retrospective study of 65 patients with symptomatic cervical ICA occlusion from January 2011 to December 2013. The collateral vessels (anterior and posterior communicating arteries, ophthalmic artery, and leptomeningeal arteries) were assessed by CTA. The outcome at 3 months was defined as poor if the modified Rankin Scale score was ≥3., Results: The mean age of subjects was 57 ± 11.6 years (range, 32-80 years), and 92% were men. Thirty-three (50.8%) patients had poor outcome. Absence of the ipsilateral ophthalmic artery, poor leptomeningeal collaterals, and <2 collaterals were predictors of stroke severity at onset and poor 3-month outcome in univariate analysis. In the multiple logistic regression analysis, inadequate flow through the secondary collaterals (ipsilateral ophthalmic artery or leptomeningeal collaterals; OR, 4.5; 95% CI, 1.4-14.9; P = .01) and higher NIHSS score at stroke onset (OR, 19.2; 95% CI, 2.2-166.2; P = .007) independently predicted poor outcome at 3 months., Conclusions: Assessment of collateral circulation with CTA can be a useful predictor of 3-month outcome in patients with symptomatic cervical ICA occlusion., (© 2017 by American Journal of Neuroradiology.)

Objective: To describe the clinical characteristics of a cohort of south Indian children with probable autoimmune encephalopathy from a tertiary care academic hospital and to compare this data with the existing literature., Methods: Patients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction were identified. Common infectious causes were excluded. Clinical characteristics, investigations, management and outcome were analyzed., Results: Thirteen patients were included in the study; 12 were females (92.3 %) and mean age was 9.6 y. Most common presentation was behavior change (13 patients) followed by seizures (11 patients). Three patients showed lymphocytic pleocytosis in CSF and one patient had oligoclonal bands. Initial MRI was normal in all patients except in one. Most common EEG abnormality was mild background slowing. Only one child had ovarian tumor. S.NMDA receptor antibody was positive in 10 patients (83 %), and all of them received immunotherapy. Six out of 13 children were followed up for more than 1 y (mean - 21 mo). Recurrence was noted in 4 out of 6 patients (66 %). On last follow-up, good recovery was seen in 2 children (33 %), moderate disability in 3 (50 %) and severe disability in 1 (16 %)., Conclusions: The clinical characteristics and outcome of one of the largest single center cohort of Indian children with autoimmune encephalopathy is reported. Autoimmune encephalopathy should be considered as a differential diagnosis in the acute and subacute encephalopathies of childhood and treating pediatrician should be aware of this entity.

Background: Immunological causes of atypical parkinsonism/Parkinson plus syndromes are rare., Objective: To study the clinical and laboratory features and treatment outcome of autoimmune atypical parkinsonism., Methods: Retrospective case series. Patients with atypical parkinsonism and positive antibodies were identified retrospectively. Those who received immunotherapy (intravenous methyl prednisolone 1g daily for five days followed by mycophenylate mofetil 2g daily or azathioprine 2-3mg/kg/day) and consented for publication of non-anonymized videos were included., Results: There were ten cases (nine males, age range 49-75years, disease duration 2months to 13years, follow-up 1-7months) of atypical parkinsonism [probable multiple system atrophy (MSA)-2, possible progressive supranuclear palsy (PSP)-1, probable PSP-3]. Eight had new uncharacterized neuronal antibodies, leucine rich glioma associated protein 1 (LGI1) antibody in one, and the other had another uncharacterized neuronal antibody along with LGI1 antibody. Four had abnormal CSF. There was a prompt, dramatic improvement in terms of Unified Parkinson Disease Rating Scale motor scale and or modified Rankin Scale as well as improvement in eye movement, postural instability, cerebellar, autonomic and non-motor symptoms. Two had reappearance of symptoms on discontinuing steroids and improvement on restarting. One died of infection despite good recovery of encephalopathy and parkinsonism., Conclusion: Autoimmune atypical parkinsonism is characterized by atypical parkinsonism with neuronal specific antibodies, sometimes associated with abnormal CSF and significant response to immunotherapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Context: Autoimmune encephalitis is a heterogeneous disorder which is being diagnosed with increasing frequency. The diagnosis of these disorders is based on the detection of autoantibodies and characteristic clinical profiles., Aims: We aimed to study the antibody profile in encephalitis patients with suspected autoimmune etiology presenting to a tertiary care center., Settings and Design: The subjects were selected by screening all patients with clinical profile suggesting autoimmune encephalitis admitted in the neuromedical intensive care unit (ICU) of a tertiary care center in South India., Materials and Methods: Patients who fulfilled modified Zuliani et al.'s, criteria for autoimmune encephalitis were identified during the period December 2009-June 2013. Blood samples from these subjects were screened for six neuronal antibodies., Statistical Analysis Used: Chi-square test was applied to compare the antibody positive and negative patients., Results: Out of 1,227 patients screened, 39 subjects (14 males: 25 females) were identified with a mean age of 15.95 years and 19 cases were assessed in the acute and 20 in the convalescent phase of the illness. Seizure (87.8 %) was the most common presenting symptom; status epilepticus occurred in 23 (60.5%) patients during the course of the illness. Fourteen (35.9%) patients were N-methyl-D-aspartate receptor (NMDAR) antibody-positive and all were negative for the other antibodies tested., Conclusions: One-third of patients presenting with acute noninfective encephalitis would be positive for NMDAR antibodies with the remaining two-thirds with clinically suspected autoimmune encephalitis being antibody-negative. There are few markers in the clinical and investigative profiles to distinguish antibody-positive and -negative patients.

Paraneoplastic neurological syndromes (PNS) are rare disorders associated with cancer, not caused by direct invasion, metastasis or consequences of treatment. They are usually autoimmune in nature. Often, PNS precedes the manifestations of cancer. Onconeural antibodies are important in the diagnosis and management of these disorders. These antibodies are specific for the malignancy rather than for a particular neurological syndrome. Often, there are different antibodies associated with the same syndrome. Multiple antibodies are also known to coexist in a given patient with malignancy. While investigating a patient for suspected PNS, the entire gamut of onconeural antibodies should be investigated so as not to miss the diagnosis. In 30-40% of the cases, PNS can occur without antibodies. Investigations for identifying the underlying cancer can be directed by the antibody panel. If conventional screening for cancer is negative, a positron emission scanning/computed tomography scan can be useful. Patients need follow-up surveillance for cancer if not detected in the first instance. Cancer detection and treatment, immunotherapy and supportive care are important components of treatment of PNS. Immunotherapy is very effective in PNS associated with cell membrane-associated antibodies like voltage-gated potassium channel complex, NMDA receptor antibodies and voltage-gated calcium channel antibodies. Immunotherapy includes steroids, IVIgG, plasmaphereis, cytotoxic medications and rituximab. Supportive therapy includes symptomatic treatment with antiepileptic and analgesic medications, physiotherapy, speech therapy and occupational therapy. PNS can mimic any neurologic syndrome. A high index of clinical suspicion is important for early diagnosis and prompt management and better outcome.

We undertook a community-based case-control study on persons with active epilepsy residing in Kerala, southern India. Using a standardized questionnaire, we collected information from 362 cases and 362 controls. In the final multivariate model, family history of epilepsy (odds ratio=7.8, 95% confidence interval=3.2-18.8, P=0.000), antecedent history of febrile seizures (7.7, 4.3-14.0, 0.000), birth by complicated delivery (6.8, 2.1-21.8, 0.001), and neonatal seizures (7.8, 1.7-35.4, 008) emerged as strong independent predictors of epilepsy, followed in decreasing order by mental retardation, prematurity, maternal age 30, perinatal distress, and incomplete immunization. There were more similarities than differences in the distribution of risk factors between generalized and localization-related epilepsy syndromes. Our findings suggest interplay between genetic and acquired factors in the pathogenesis of epilepsies, and underscore the need for improvement in obstetric and neonatal care to minimize the epilepsy burden in low-income countries.

Background: Intracranial infectious aneurysms (IA) are infrequent, but can be fatal., Objectives: To compare the clinical profile of IAs associated with intravascular/systemic infection like infective endocarditis with that associated with local infections like meningitis, orbital cellulitis and cavernous sinus thrombosis., Methods: We analysed all cases of IA, treated in this Institute from 1976 to 2003, in order to identify prognostic factors., Results: There were 25 persons (mean age 24.8+/-17.3 years, males 17) with 29 IA (carotid circulation 19, vertebrobasilar circulation 10). Headache (83%) and fever (67%) were the most common presenting symptoms. In contrast to noninfectious aneurysms, intracerebral haemorrhage (60%) and focal signs were more common than subarachnoid haemorrhage (7%) with IA. Sources of infection were cardiac (10), meningitis (12), orbital cellulitis (2) or uncertain (1). Infective agents included bacteria (18), fungi (4), and tubercle bacilli (3). Fifteen IA were distal and 14 were proximal. IAs associated with meningitis were proximal (75%) while those associated with cardiac diseases preferentially involved carotid territory and were distal (p=0.013). The overall mortality was 32%. Survivors were younger than those who expired (p=0.015). Of the sixteen patients treated medically, seven recovered (44%), others (56%) had treatment failure (three died and six required surgery later). Another five patients underwent early surgery (one died). Mortality of IA was significantly higher with meningitis, fungal aetiology and vertebrobasilar location., Conclusions: IAs associated with local infections like meningitis had different clinical profile as compared to IAs associated with intravascular/systemic infections like infective endocarditis.