Regulation of Keap1-Nrf2 axis in temporal lobe epilepsy-hippocampal sclerosis patients may limit the seizure outcomes.

BACKGROUND: Accumulation of reactive oxygen species (ROS) exacerbates neuronal loss during seizure-induced excitotoxicity. Keap1 (Kelch-like ECH-associated protein1)-nuclear factor erythroid 2-related factor 2 (Nrf2) axis is one of the known active antioxidant response mechanisms. Our study focused on finding the factors influencing Keap1-Nrf2 axis regulation in temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) patients. METHODS: Based on post-surgical follow-up data, patient samples (n = 26) were categorized into class 1 (completely seizure-free) and class 2 (only focal-aware seizures/auras), as suggested by International League Against Epilepsy (ILAE). For molecular analyses, double immunofluorescence assay and Western blot analysis were employed. RESULTS: A significant decrease in expression of Nrf2 (p < 0.005), HO-1; p < 0.02) and NADPH Quinone oxidoreductase1 (NQO1; p < 0.02) was observed in ILAE class 2. Keap1 (p < 0.02) and histone methyltransferases (HMTs) like SetD7 (SET7/9; SET domain-containing 7 histone lysine methyltransferase) (p < 0.009) and enhancer of zeste homolog 2 (EZH2; p < 0.02) and methylated histones viz., H3K4me1 (p < 0.001), H3K9me3 (p < 0.001), and H3K27me3 (p < 0.001) was upregulated in ILAE class 2. Nrf2-interacting proteins viz., p21 (p < 0.001) and heat shock protein 90 (HSP90; p < 0.03) increased in class 1 compared to class 2 patients. CONCLUSION: Upregulation of HMTs and methylated histones can limit phase II antioxidant enzyme expression. Also, HSP90 and p21 that interfere with Keap1-Nrf2 interaction could contribute to a marginal increase in HO-1 and NQO1 expression despite histone methylation and Keap1. Based on our findings, we conclude that TLE-HS patients prone to seizure recurrence were found to have dysfunctional antioxidant response, in part, owing to Keap1-Nrf2 axis. The significance of Keap1-Nrf2 signaling mechanism in generation of phase II antioxidant response. Keap1-Nrf2 controls antioxidant response through regulation of phase II antioxidant enzymes like HO-1 (heme oxygenase-1), NQO1 (NADPH-Quinone Oxidoreductase1), and glutathione S-transferase (GST). Release of Nrf2 from negative regulation by Keap1 causes its translocation into nucleus, forming a complex with cAMP response-element binding protein (CBP) and small Maf proteins (sMaf). This complex subsequently binds antioxidant response element (ARE) and elicits and antioxidant response involving expression of phase II antioxidant enzymes. Reactive oxygen species (ROS) modify Cysteine 151 residue, p62 (sequsetosome-1), and interacts with Nrf2- binding site in Keap 1. p21 and HSP90 prevent Nrf2 interaction with Keap1. At transcriptional level, histone methyltransferases like EZH2 (enhancer of zeste homologue2), and SetD7 (SET7/9; SET domain-containing 7 histone lysine methyltransferase) and corresponding histone targets viz., H3K27me3, H3K9me3, and H3K4me1 influence Nrf2 and Keap1 expression respectively.

Non-Arteritic Anterior Ischaemic Optic Neuropathy - Myths and Misconceptions: Experience from a Tertiary Care Centre in North India.

We prospectively evaluated 22 consecutive patients (24 eyes) suffering from non-arteritic anterior ischaemic optic neuropathy (NAION) at a tertiary care centre in Northern India. The mean age was 51.7 years. Visual loss on awakening was noticed only in three (12.5%) eyes. Six (27.3%) patients had headache while three (9.7%) patients had retro-orbital pain at the onset of visual loss. Peripapillary haemorrhages were seen in two (8.3%) eyes. At follow up, only one eye showed improvement in visual acuity. The results of our study suggest that NAION may not always present with the classic clinical picture. Accordingly, a high index of suspicion remains the key to correct diagnosis.

Design, synthesis and biological evaluation of novel inosine 5'-monophosphate dehydrogenase (IMPDH) inhibitors.

This study is based on our attempts to further explore the structure-activity relationship (SAR) of VX-148 (3) in an attempt to identify inosine 5'-mono-phosphate dehydrogenase (IMPDH) inhibitors superior to mycophenolic acid. A five-point pharmacophore developed using structurally diverse, known IMPDH inhibitors guided further design of novel analogs of 3. Several conventional as well as novel medicinal chemistry strategies were tried. The combined structure- and ligand-based approaches culminated in a few analogs with either retained or slightly higher potency. The compounds which retained the potency were also checked for their ability to inhibit human peripheral blood mononuclear cells proliferation. This study illuminates the stringent structural requirements and strict SAR for IMPDH II inhibition.

Use of 30 gauge needle to prevent hypotony during silicone oil removal.

Silicone oil (SO) is used as an intraocular tamponade after complex vitreoretinal surgeries because of its properties such as transparency, inertness, high surface tension, and interfacial tension with water. The only disadvantage of SO tamponade is the need for a second surgery for its removal. However, there is a risk of ocular hypotony soon after the removal of the infusion cannula, especially in retinal vascular conditions, such as diabetic retinopathy. We hereby present a silicone oil removal (SOR) technique using a 30 G needle that prevents intraocular hypotony during SOR.

Comparative Evaluation of the Sealing Ability of Mineral Trioxide Aggregate (MTA)-Based, Resin-Based, and Zinc Oxide Eugenol Root Canal Sealers: An In Vitro Study.

Root canal therapy is a crucial procedure in endodontics that is done to achieve complete obliteration of the root canal space. The success of this therapy depends on achieving a proper seal, which is facilitated using root canal sealers. This study aimed to compare the apical sealing ability of three different root canal sealers: MTA Fillapex, AH Plus, and zinc oxide eugenol (ZOE), using the dye penetration method. Forty freshly extracted single-rooted human maxillary incisors were collected and prepared for the study. The root canals were instrumented using the ProTaper system, and the canals were then obturated using the lateral condensation technique with the respective sealers. After one week of storage, the samples were coated with nail varnish, immersed in a rhodamine B dye solution, and then sectioned longitudinally. The depth of dye penetration was measured, and the results were analyzed statistically. The results revealed significant differences in apical leakage among the three experimental groups. Group 2 (AH Plus) showed the minimum leakage with a mean of 0.13 mm, while Group 4 (no sealer) exhibited the maximum leakage with a mean of 4.49 mm. Group 3 (ZOE) showed an intermediate level of leakage with a mean of 2.37 mm. The statistical analysis confirmed the significant difference in mean leakage among the groups. The findings of this study indicate that AH Plus exhibited superior apical sealing ability compared to MTA Fillapex and ZOE. AH Plus is a resin-based sealer known for its dimensional stability. On the other hand, MTA Fillapex, a newly introduced sealer containing mineral trioxide aggregate, resin, and silica, showed promising sealing properties but had slightly higher leakage compared to AH Plus. ZOE, a traditional sealer, demonstrated relatively higher leakage than the other sealers. In conclusion, choosing a root canal sealer is crucial in achieving a successful endodontic treatment outcome. AH Plus demonstrated superior apical sealing ability among the three sealers tested. Further research and long-term clinical studies are warranted to validate these findings and assess the impact of sealer choice on treatment outcomes and post-endodontic healing.

Leukemoid reaction, a rare manifestation of autoimmune hemolytic anemia in a case of small duct primary sclerosing cholangitis.

A 48 year old lady presented with jaundice and exertional breathlesness. Her laboratory reports showed anaemia, reticulocytosis, leucocytosis, elevated Lactate Dehydrogenase (LDH), alkaline phosphatase levels, hyperbillirubinemia and positive direct Coomb's test. After ruling out all the other causes of autoimmunity and hemolytic anemia, she was diagnosed as leukemoid reaction due to autoimmune hemolytic anemia with primary sclerosing cholangitis. Patient showed immediate improvement after corticosteroids.

A case of eosinophilic granulomatous polyangiitis with concurrent central and peripheral nervous system involvement.

Eosinophilic granulomatous polyangiitis (EGPA) like other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has multisystemic involvement. It commonly manifests with prodromal pulmonary involvement as asthma, chronic sinusitis followed by systemic vasculitic complications associated with blood and tissue eosinophilia. Central nervous system manifestations at presentation are uncommon compared with peripheral nervous system involvement. Vasculitic neuropathy in EGPA commonly presents as mononeuritis multiplex but rarely as polyradiculopathy. Late onset EGPA often presents with systemic involvement, and early diagnosis is a key to prevent further complications. The neuropathy in late onset EGPA is often refractory to immunosuppression and corticosteroids treatment. We report a case of EGPA with late onset asthma presenting with acute infarct and demyelinating polyradiculoneuropathy that progressed with bulbar paralysis and profound dysautonomia. This illustrates simultaneous involvement of central and peripheral nervous system with EGPA. Autonomic dysfunction can occur in patients of EGPA with multisystem involvement, which may predict severe complications.

Anxiety, depression, and psychosocial adjustment in people with epilepsy.

Objective: Effect of psychological disorders on social functioning in people with epilepsy (PWE) is not extensively reported. We evaluate psychosocial functioning in PWE attending an outpatient clinic and aim to understand the differences in psychosocial functioning between anxiety, depression, and coexisting anxiety and depression in PWE. Materials and Methods: A prospective evaluation of psychosocial functioning of 324 consecutive adult PWE attending outpatient epilepsy clinic was done using self-reported Washington Psychosocial Seizure Inventory. The study population was divided in four groups - without psychological disorders, anxiety, depression, and both anxiety and depression. Results: The mean age of study population was 25.90 ± 6.22 years. Anxiety was noted in 73 (22.5%), depression in 60 (18.5%), and both anxiety and depression were seen in 70 (21.6%) and the rest had normal psychosocial function. There were no significant differences across all the four sub-groups for sociodemographics. Psychosocial functioning did not differ significantly between PWE with normal psychosocial function and PWE with anxiety alone. However, psychosocial functioning scores were worse in PWE with depression and PWE with both anxiety and depression when compared to PWE with normal psychosocial function. Conclusion: In the present study of PWE attending an outpatient epilepsy clinic, one-fifth of PWE had both anxiety and depression. Psychosocial functioning in PWE with anxiety was similar to otherwise healthy/normal PWE, whereas PWE with depression showed poor psychosocial functioning. Role of psychological interventions on psychosocial aspects of epilepsy should be studied extensively in future.

Dopamine and Glutamate Crosstalk Worsen the Seizure Outcome in TLE-HS Patients.

Temporal lobe epilepsy (TLE), accompanied by hippocampal sclerosis (HS), is the most common form of drug-resistant epilepsy (DRE). Nearly 20% of the patients showed seizure recurrence even after surgery, and the reasons are yet to be understood. Dysregulation of neurotransmitters is evident during seizures, which can induce excitotoxicity. The present study focused on understanding the molecular changes associated with Dopamine (DA) and glutamate signaling and their possible impact on the persistence of excitotoxicity and seizure recurrence in patients with drug-resistant TLE-HS who underwent surgery. According to the International League against Epilepsy (ILAE) suggested classification for seizure outcomes, the patients (n = 26) were classified as class 1 (no seizures) and class 2 (persistent seizures) using the latest post-surgery follow-up data to understand the prevalent molecular changes in seizure-free and seizure-recurrence patient groups. Our study uses thioflavin T assay, western blot analysis, immunofluorescence assays, and fluorescence resonance energy transfer (FRET) assays. We have observed a substantial increase in the DA and glutamate receptors that promote excitotoxicity. Patients who had seizure recurrence showed a significant increase in (pNR2B, p < 0.009; and pGluR1, p < 0.01), protein phosphatase1γ (PP1γ; p < 0.009), protein kinase A (PKAc; p < 0.001) and dopamine-cAMP regulated phospho protein32 (pDARPP32T34; p < 0.009) which are critical for long-term potentiation (LTP), excitotoxicity compared to seizure-free patients and controls. A significant increase in D1R downstream kinases like PKA (p < 0.001), pCAMKII (p < 0.009), and Fyn (p < 0.001) was observed in patient samples compared to controls. Anti-epileptic DA receptor D2R was found to be decreased in ILAE class 2 (p < 0.02) compared to class 1. Since upregulation of DA and glutamate signaling supports LTP and excitotoxicity, we believe it could impact seizure recurrence. Further studies about the impact of DA and glutamate signaling on the distribution of PP1γ at postsynaptic density and synaptic strength could help us understand the seizure microenvironment in patients. Dopamine, Glutamate signal crosstalk. Diagram representing the PP1γ regulation by NMDAR negative feedback inhibition signaling (green circle-left) and D1R signal (red circle-middle) domination over PP1γ though increased PKA, pDARPP32T34, and supports pGluR1, pNR2B in seizure recurrent patients. D1R-D2R hetero dimer activation (red circle-right) increases cellular Ca2+ and pCAMKIIα activation. All these events lead to calcium overload in HS patients and excitotoxicity, particularly in patients experiencing recurrent seizures.

Efficacy of a single injection of brolucizumab in neovascular age-related macular degeneration on visual acuity and micromorphometry.

Purpose: To assess short-term efficacy of a single injection of brolucizumab in neovascular AMD. Methods: This was a multicenter, retrospective chart review of 25 eyes of 25 patients who received a single injection of brolucizumab. Visual acuity (VA) and optical coherence tomography (OCT) features such as central subfield thickness (CSFT), subretinal fluid (SRF), intraretinal fluid, and pigment epithelial detachment (PED) were recorded at baseline, first month, and third month. Results: Of the 25 eyes, 14 eyes were treatment-naïve and 11 eyes had received previous injections. VA improved from 0.68 ± 0.59 log MAR at baseline to 0.31 ± 0.43 log MAR at the end of 3 months. SRF height in first and third month was significantly reduced from baseline (P < 0.001). Subretinal hyperreflective material height significantly reduced from baseline (P value 0.008 at first month and 0.01 at third month, respectively). CSFT was 464.16 ± 247.97 microns at baseline and showed a significant reduction in first month (P < 0.001) and third month (P < 0.001). There was a significant reduction of PED height from baseline at both follow-ups. None of the eyes showed a recurrence of fluid at the end of 3 months. Conclusion: Our study demonstrated sustained improvement in VA and OCT parameters after a single injection of brolucizumab at 3 months. A longer follow-up may demonstrate even farther effects of a single injection.

Long-Term Seizure Freedom, Resolution of Epilepsy and Perceived Life Changes in Drug Resistant Temporal Lobe Epilepsy With Hippocampal Sclerosis: Comparison of Surgical Versus Medical Management.

BACKGROUND: Outcome of temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) has rarely been evaluated exclusively. OBJECTIVE: To compare long-term seizure freedom, resolution of epilepsy, and perceived life changes in patients with drug-resistant TLE-HS who underwent surgery vs those who opted for best medical management. METHODS: In this retrospective longitudinal study, 346 patients with TLE-HS who underwent surgery were compared with 325 who received best medical management. Predictors for long-term remission, resolution of epilepsy, and seizure recurrence were analyzed. RESULTS: The duration of follow-up ranged from 3-18 (mean 12.61) years. The average age of study population was 28.54 ± 12.27 years with 321 (47.8%) women. Age at onset of epilepsy (11.84 ± 8.48 vs 16.29 ± 11.88; P ≤ .001) was lower, and duration of epilepsy (15.65 ± 9.33 vs 12.97 ± 11.44; P < .001) was higher in the surgery group. Seizure freedom at 3 (81.8 vs 19.0%; P < .001), 5 (73% vs 16.1%; P < .001), and 10 years (78.3% vs 18.5; P < .001) and resolution of epilepsy (30.5% vs 0.6%; P < .001) was higher in the surgery group. The overall perceived life changes score was higher in the surgery group (80.96 ± 25.47 vs 66.24 ± 28.13; P < .001). At long-term follow-up (≥10 years), the presence of an aura was the strongest predictor for resolution of epilepsy (ß: 2.29 [95% CI; 1.06-4.93]; P = .035), whereas acute postoperative seizures (APOS) (ß: 6.06 [95% CI 1.57-23.42]; P < .001) and an abnormal postoperative EEG (ß: 0.222 [95% CI 0.100-0.491]; P < .001) were predictors of persistent seizures. Seizure freedom both at 3 and 5 years predicted seizure freedom at 10 years. CONCLUSION: Surgery for drug-resistant TLE-HS was associated with higher rate of long-term seizure-freedom, resolution of epilepsy, and reduction of anti-seizure medications with improvement in perceived life changes compared with best medical management. The presence of an aura was predictor for resolution of epilepsy while APOS and an abnormal postoperative EEG were predictors of persistent seizures.

First contact investigations and compliance to treatment in patients with uveitis.

AIM: To ascertain the pattern of investigations at first contact in uveitic patients and evaluate compliance to treatment. METHODS: An observational study comprised of 201 uveitic patients presenting for the first time to our centre from January 2019 to June 2020. Detailed information regarding systemic investigations undertaken by specialists at the time of first contact and the cost of these investigations were reviewed on the first visit to our centre. Compliance with the treatment was determined and reasons behind non-compliance were evaluated on the first follow-up in patients who had no improvement in clinical signs and symptoms. RESULTS: The mean age of the study group was 35.35±14.1y and gender composition was 59.7% males and 40.3% females. Anterior uveitis was observed in 45.3% of patients, intermediate uveitis in 31.8% of patients, posterior uveitis in 14.9% of patients and panuveitis in 8.0% of patients. Association with a systemic disease was evident in 17.9% of patients. When compared with standard guidelines and uveitis patterns, systemic investigations were identified to be relevant only in 38.3% of patients. Non-compliance to treatment was documented in 22.4% of patients. Common reasons for non-compliance were inadequate counselling by the treating physician about treatment in 26.7% of patients and a busy schedule at work/school in 22.2% of patients. CONCLUSION: Significant number of investigations performed at first contact is found to be contrary to standard guidelines and are not contributory to the care. About a quarter of patients in this study are found to be non-compliant with the treatment. Compliance is more challenging to achieve in school-going children and working adults. The availability of comprehensive, periodically updated, evidence-based guidelines on the role of investigations and the use of trained counsellors may help to channelize proper evaluation and improve compliance to treatment, respectively, in patients with uveitis.

Protein Nanoparticles for Enhanced Oral Delivery of Coenzyme-Q10: in Vitro and in Silico Studies.

Coenzyme-Q10 (CoQ10) is a hydrophobic benzoquinone with antioxidant and anti-inflammatory properties. It is known to reduce oxidative stress in various health conditions. However, due to the low solubility, permeability, stability, and poor oral bioavailability, the oral dose of CoQ10 required for the desired therapeutic effect is very high. In the present study, CoQ10 is encapsulated into two milk derived proteins ß-lactoglobulin and lactoferrin (BLG and LF) to produce self-assembled nanostructures of around 100-300 nm with high encapsulation efficiency (5-10% w/w). Both CoQ10-BLG and CoQ10-LF nanoparticles (NPs) significantly improved the aqueous solubility of CoQ10 60-fold and 300-fold, compared to CoQ10 alone, which hardly dissolves in water. Insight into the difference in solubility enhancement between BLG and LF was obtained using in silico modeling, which predicted that LF possesses multiple prospective CoQ10 binding sites, potentially enabling greater loading of CoQ10 on LF compared to BLG, which was predicted to be less capable of binding CoQ10. At pH 7.4, CoQ10-LF NPs showed a burst release between 30 min and 2 h then plateaued at 12 h with 30% of the total drug released over 48 h. However, pure CoQ10-BLG and pure CoQ10 had a significantly lower release rate with less than 15% and 8% cumulative release in 48 h, respectively. Most importantly, both BLG and LF NPs significantly improved CoQ10 permeability compared to the pre-dissolved drug across the Caco-2 monolayer with up to 2.5-fold apparent permeability enhancement for CoQ10-LF─further confirming the utility of this nanoencapsulation approach. Finally, in murine macrophage cells (J774A.1), CoQ10-LF NPs displayed significantly higher anti-ROS properties compared to CoQ10 (predissolved in DMSO) without affecting the cell viability. This study paves the way in improving oral bioavailability of poorly soluble drugs and nutraceuticals using milk-based self-assembled nanoparticles.

Prevalence of carpal tunnel syndrome among dairy workers.

BACKGROUND: The purpose of this study was to determine the prevalence of carpal tunnel syndrome (CTS) among dairy workers. METHODS: Sixty-six dairy parlor workers and 58 non-parlor workers at dairies in Texas, New Mexico, and Colorado participated in structured interviews regarding demographics, work history, and hand symptoms. All participants had nerve conduction studies performed on both hands across the carpal tunnel. A CTS case definition was based on the presence of characteristic CTS symptoms and an abnormal median mononeuropathy across the carpal tunnel. RESULTS: The prevalence of CTS among the dairy parlor workers was 16.6% and 3.6% among non-parlor workers. The difference was found to be statistically significant (P < 0.05) with an odds ratio of 5.3, CI (1.1-25.5). CONCLUSIONS: The results of this study indicate that CTS is a significant challenge for dairy parlor workers. The prevalence of CTS was found to be significantly higher among dairy workers performing tasks in the milking parlor as opposed to workers performing tasks in other areas of the dairy farm. The results emphasize the need for administrative and engineering controls to limit the exposure to physical risk factors that are associated with upper limb disorders such as CTS.

Analgesic and anti-inflammatory activity of ß-sitosterol isolated from Nyctanthes arbortristis leaves.

Nyctanthes arbortristis Linn. (Oleaceae) is one of the well-known Indian medicinal plant. Various extracts of leaves of the plant were screened for analgesic activity by hot plate test and acetic acid-induced writhings and anti-inflammatory activity by carrageenan-induced hind paw edema method at the dose of 50 mg/kg, i.p. Petroleum ether extract was found to be most active and hence subjected to activity-guided fractionation. Results showed that ß-sitosterol (5, 10 and 20 mg/kg, i.p.) was responsible for the significant and dose-dependent activity comparable with the standard extract. ß-Sitosterol from N. arbortristis leaves might be responsible for analgesic and anti-inflammatory activity.

Determinants of mortality and long-term outcome in children with refractory and super refractory status epilepticus.

AIM: To evaluate factors associated with progression of convulsive refractory status epilepticus(RSE) to super refractory status epilepticus(SRSE) and long term outcome in children. MATERIALS AND METHODS: In this open cohort study, data of children admitted with convulsive RSE from 2010 to 2018 was retrospectively analyzed. The outcome at two years was graded according to the Glasgow outcome scale(GOS). RESULTS: Fifty six children formed study population, 24 progressed to SRSE. The mean age of the study population was 9.38 ± 4.28(2-16) years. There was no significant difference for age between SRSE and RSE children (9.53 ± 4.50 years vs. 9.17 ± 4.06 years; p = 0.756). Acute symptomatic aetiology was the most common aetiology for RSE (57.1%) and SRSE (54.2%). There were no differences for aetiology between children who progressed to SRSE and those who did not. Mean length of stay in the NICU was 13.54 ± 17.53 days and children who progressed to SRSE had a longer length of stay in NICU (4.78 ± 3.03 days vs. 25.21 ± 21.77 days; p < 0.001). The mortality was 14.2%. Acidosis was more common in children who died (27.1% vs. 87.5%;p < 0.001). There was no significant difference in the mortality between RSE and SRSE (9.4% vs. 20.8%; p = 0.268). At latest follow up 34 (60.7%) children had good outcome. Poor outcome was more common in children who progressed to SRSE(29.4% vs. 63.6%;p < 0.015). CONCLUSION: Acute symptomatic etiology is more frequent in children with RSE and SRSE. Progression to SRSE did not significantly increase mortality but associated with poor GOS outcome. Encouragingly, 60% of children had good outcome.

Endoplasmic reticulum stress and unfolded protein accumulation correlate to seizure recurrence in focal cortical dysplasia patients.

Epileptic seizures occur due to an imbalance between excitatory and inhibitory neurosignals. The excitotoxic insults promote the accumulation of reactive oxygen species (ROS), unfolded proteins (UFP) aggregation, and sometimes even cell death. The epileptic brain samples in our study showed significant changes in the quantity of UFP accumulation. This part explored the efficiency of ER stress and autophagy responses at neutralizing the UFP using resected epileptic brain tissue samples. Meanwhile, we regularly observed these patients' post-surgical clinical data to find the recurrence of seizures. According to International League against Epilepsy (ILAE) suggestions, we classified the patients (n = 26) as class 1 (completely seizure-free), class 2 (less frequent seizures or auras), and class 3 (auras with < 3 seizures per year). The classification helped us understand the reason for variations in the UFP accumulation in patient samples. We have observed the protein levels of ER chaperone, glucose-regulated protein 78 kDa (GRP78/BiP), inositol-requiring enzyme 1α (IRE1α), X box-binding protein 1 s (XBP1s), eukaryotic translation initiation factor 2α (peIF2α), C/EBP homologous protein (CHOP), NADPH oxidase (NOX2), and autophagy proteins like BECLIN1, ATG 7, 12, 5, 16, p62, and LC3. Our results suggested that ER stress response limitation may contribute to seizure recurrence in epilepsy patients, particularly in classes 2 and 3. In addition, we have observed significant upregulation of ER stress-dependent apoptosis initiation factor CHOP in these patients. These results indicate that understanding the ER stress response pattern infers the possibility of post-surgical outcomes in focal cortical dysplasia (FCD) patients.

Impact of the COVID-19 Pandemic on the Frequency, Clinical Spectrum and Outcomes of Pediatric Guillain-Barré Syndrome in India: A Multicentric Ambispective Cohort Study.

Objective: To study impact of COVID-19 pandemic on frequency, clinical/electrophysiological profile and treatment outcomes in pediatric Guillain-Barré syndrome (GBS). Background: GBS is the most frequent cause of pediatric acute flaccid paralysis. The effect of the COVID-19 pandemic on pediatric GBS is unclear in the literature. Methods: We conducted an ambispective, multicentric, cohort study involving 12 of 27 centres in GBS Consortium, during two periods: pre-COVID-19 (March-August 2019) and during COVID-19 (March-August 2020). Children ≤12 years who satisfied National Institute of Neurological Diseases and Stroke criteria for GBS/variants were enrolled. Details pertaining to clinical/laboratory parameters, treatment and outcomes (modified Rankin Scale (mRS) at discharge, GBS Disability score at discharge and 3 months) were analysed. Results: We enrolled 33 children in 2019 and 10 in 2020. Children in 2020 were older (median 10.4 [interquartile range 6.75-11.25] years versus 5 (2.5-8.4) years; P = 0.022) and had more sensory symptoms (50% versus 18.2%; P = 0.043). The 2020 group had relatively favourable mRS at discharge (median 1 (1-3.5) versus 3 (2-4); P = 0.042) and GBS disability score at 3 months (median 0 (0-0.75) versus 2 (0-3); P = 0.009) compared to 2019. Multivariate analysis revealed bowel involvement (P = 0.000) and ventilatory support (P = 0.001) as independent predictors of disability. No child in 2020 had preceding/concurrent SARS-CoV2 infection. Conclusions: The COVID-19 pandemic led to a marked decline in pediatric GBS presenting to hospitals. Antecedent illnesses, clinical and electrophysiological profile of GBS remained largely unchanged from the pre-pandemic era.