Acute bilateral sensorineural hearing loss as presentation of leptomeningeal metastases.

We describe a rare occurrence of bilateral acute severe sensorineural hearing loss in a middle-aged man that heralded the diagnosis of metastatic gastric cancer.

Impact of weight reduction on structural and functional parameters of the optic nerve in idiopathic intracranial hypertension.

PURPOSE: To evaluate the effect of weight reduction on the structural and functional parameters of the optic nerve in established cases of papilledema in Idiopathic Intracranial Hypertension (IIH). METHODS: A prospective observational study in early and established cases of papilledema in IIH presenting from December 2019 to February 2021. Functional parameters (visual acuity, contrast sensitivity, mean deviation, VER), structural parameters (RNFL, GCL-IPL, and optic disc height), and clinical grading of papilledema were measured at baseline and every 6 weeks for 6 months. All patients underwent medical (oral acetazolamide) and diet therapy. RESULTS: Mean body mass index (BMI) at presentation was 26.32 ± 3.52 kg/m² and the mean change in BMI over 6 months was 1.27 ± 0.50 kg/m². 67% of eyes had papilledema of grades 2-3 at the presentation. At the end of 6 months, 75% of eyes had grade 1 papilledema while 13% showed complete resolution. A reduction of 5.32 ± 3.58 in mean deviation (r = 0.316; p-value 0.01) and gain in VER P100 amplitude of 4.2 ± 2.7 µV (r = 0.40; p-value 0.003) were noted over 6 months with reduction in BMI over 6 months. A statistically significant reduction in optic disc height (ODH) was noticed with BMI reduction over 6 months (p = 0.0007; r = 0.45).A reduction of 1.72 ± 0.90 kg/m² (equivalent to 6.53% weight loss) in BMI was associated with a four-grade change in clinical grading of papilledema. CONCLUSION: Reduction in BMI had a significant impact on both structural and functional parameters of the optic nerve in IIH. The involvement of a well-certified dietician should be an integral part of treatment in IIH.

Safety and efficacy of N-acetylcysteine (NAC) as an adjunct to standard treatment in patients with acute ischemic stroke: a randomized controlled pilot trial (NACTLYS).

There is a pressing clinical need for thrombolytic agents that can effectively disaggregate arterial thrombi in acute ischemic stroke without significantly increasing the risk of bleeding. This pilot study aimed to investigate the safety and efficacy of N-acetylcysteine (NAC) as an adjunctive therapy to intravenous recombinant tissue plasminogen activator (rtPA or alteplase). A randomized, open-label, blinded assessor pilot study was conducted. Patients presenting with an acute ischemic stroke within 4.5 h from onset were randomized into two groups: intravenous NAC and rtPA or rtPA alone. Primary outcomes included intracerebral hemorrhage, symptomatic intracerebral hemorrhage, extracranial bleeding, and adverse reactions. Secondary outcomes comprised major neurological improvement assessed by (National Institute of Health Stroke Scale) NIHSS at 24 h, recanalization on first run of angiography in patients who underwent thrombectomy or on repeat vascular imaging at 24 h, modified Rankin scale, and three-month mortality. Forty patients were enrolled, with 21 receiving only rtPA and 19 receiving NAC with rtPA. Baseline characteristics were comparable among groups. No significant differences were observed in adverse events (p = 0.99), intracranial hemorrhage (p = 0.21), symptomatic intracerebral hemorrhage (p = 0.47), or extracranial bleeding (p = 0.21). Median NIHSS at 24 h was significantly lower in the intervention group (p = 0.03). Functional outcomes and three-month mortality were similar between groups (p = 0.85 and p = 0.99 respectively). The co-administration of N-acetylcysteine with alteplase did not significantly alter safety profiles, morbidity, or mortality at 3 months. While no substantial differences were noted, a slightly improved early neurological outcome was observed in the intervention arm. The study's findings were constrained by a small sample size, emphasizing the necessity for future large-scale trials to comprehensively evaluate the safety and efficacy of N-acetylcysteine as a thrombolytic agent in acute ischemic stroke.Trial Registration Clinical Trials Registry India-CTRI/2019/05/019305.

Cerebrospinal fluid proteins in idiopathic intracranial hypertension: An exploratory SWATH proteomics analysis.

PURPOSE: The pathogenesis of idiopathic intracranial hypertension (IIH) is currently poorly understood. This exploratory study aimed to identify potential cerebrospinal fluid (CSF) biomarkers in IIH cases compared to controls using SWATH-MS proteomics approach. EXPERIMENTAL DESIGN: CSF samples were collected prospectively from IIH cases and control subjects which were subjected to SWATH-MS based untargeted proteomics. Proteins with fold change > 1.5 or < 0.67 and p-value < 0.05 were considered significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD027751. Statistical analysis was conducted in R version 3.6.2. RESULTS: We included CSF samples from 33 subjects, consisting of 13 IIH cases and 20 controls. A total of 262 proteins were identified in Proteinpilot search. Through SWATH analysis, we quantified 232 proteins. We observed 37 differentially expressed proteins between the two groups with 24 upregulated and 13 downregulated proteins. There were two differential proteins among overweight versus non-overweight IIH cases. Network for 23 proteins was highly connected in the interaction analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Neurosecretory, neuroendocrine, and inflammatory proteins were predominantly involved in causing IIH. This exploratory study served as a platform to identify 37 differentially expressed proteins in IIH and also showed significant differences between overweight and non-overweight IIH patients.

Clinical factors and vascular endothelial growth factor as determinants of disease progression in Indian patients with amyotrophic lateral sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Prognostication remains sub-optimally defined. We aimed to assess clinical determinants of disease progression rates in Indian patients with ALS and to assess the role of vascular endothelial growth factor (VEGF) in disease progression. METHODS: In this cross-sectional study, consecutive patients with clinically definite/probable ALS according to the revised El Escorial criteria and controls were included. Patients were classified into fast or slow progressors based on disease progression rate (DPR). Serum and CSF VEGF level was assessed for patients and controls. RESULTS: Of 142 patients recruited, 93 (65.5%) were male. Mean age at enrollment was 49.37 ± 12.65 years. Mean duration of symptoms was 20.53 ± 20.88 months. Mean DPR was 1.14 ± 0.94. Based on DPR, 81 (57%) patients were slow progressors and 61 (43%) were fast progressors. Univariate analysis demonstrated a statistically significant association of DPR with age at onset, symptom duration, time to spread, wasting of small muscles of the hand, frontal release signs, and neurophysiologic bulbar abnormalities. On multivariate analysis, age at onset and symptom duration had a significant association with disease progression. The CSF VEGF levels of ALS patients (46.18 ± 27.8) were significantly elevated compared to controls (25.95 ± 25.64 pg/ml) (p = 0.001), but not serum VEGF. CONCLUSION: Age at symptom onset and duration of disease had a significant impact on disease progression in Indian patients with ALS. CSF VEGF levels were significantly elevated in ALS compared to controls, indicating the role of CSF VEGF as a potential biomarker.

Metabolic risk factors and psychosocial problems independently explain poor sleep quality and obstructive sleep apnea symptoms among adults in urban India.

STUDY OBJECTIVES: To determine if metabolic risk factors are associated with poor sleep quality and obstructive sleep apnea-like symptoms (OSA symptoms) independent of psychosocial problems and demographic and lifestyle factors in older Indian adults. METHODOLOGY: We analyzed baseline data from adults (≥ 50 years) from a population-based cohort, the LoCARPoN study, in India. Variables were grouped as (a) demographic and lifestyle factors such as smoking, alcohol use, and physical activity; (b) psychosocial problems including symptoms of depression, anxiety, and perceived stress; and (c) metabolic risk factors including glycated hemoglobin, high-density lipoprotein, low-density lipoprotein, total cholesterol, body mass index, and hypertension. Variables were examined as predictors of poor sleep quality and OSA symptoms. Groups of variables were added stepwise to a logistic regression. Variance explained by nested models was quantified using McFadden's pseudo R2, and change was formally tested with the log-likelihood ratio test. RESULTS: Among 7505 adults, the prevalence of poor sleep quality was 16.9% (95% CI: 16.0, 17.7), and OSA symptoms were present in 7.0% (95% CI: 6.4, 7.6). Psychosocial problems had a strong independent association with both poor sleep quality (pseudo R2 increased from 0.10 to 0.15, p < 0.001) and more OSA symptoms (pseudo R2 increased from 0.08 to 0.10, p < 0.001). Metabolic risk factors had a modest independent association with sleep quality (pseudo R2 increased from 0.14 to 0.15, p < 0.01), but a strong association with OSA symptoms (pseudo R2 increased from 0.08 to 0.10, p < 0.001). CONCLUSION: Psychosocial and metabolic risk factors were independently associated with sleep quality and OSA symptoms. This fact implied that OSA symptoms may affect both mental health and physical health. Our findings have public health implications because the number and proportion of the elderly in India is increasing, while the prevalence of metabolic risk factors and psychosocial problems is high already. These facts have the potential to exacerbate not only the burden of sleep disorders and OSA symptoms but also associated cardiovascular and neurologic sequelae, further stretching the Indian health-care system.

Optical coherence tomography features and correlation of functional and structural parameters in patients of idiopathic intracranial hypertension.

Purpose: To determine the correlation between functional parameters and optical coherence tomography (OCT) features in patients of idiopathic intracranial hypertension (IIH). Methods: A prospective observational study in early and established cases of papilledema in IIH presenting from December 2017 to February 2019. Functional parameters (visual acuity, contrast sensitivity, mean deviation, VER, and MfERG) and structural parameters (RNFL, GCL-IPL, and optic disc height) were measured at baseline and every 6 weeks for 6 months. Results: At baseline, average RNFL had a moderate negative correlation with mean deviation (r = -0.45; P = 0.0007) and a positive correlation with logMAR visual acuity (r = 0.18; P = 0.17). On the contrary, baseline GCL and logMAR visual acuity had a negative correlation (r = -0.4, P = 0.02). Optic disc height (ODH) had a negative correlation with visual field mean deviation (r = -0.046; P = 0.0005). At 6 months, ODH and GCL-IPL complex had a statistically significant correlation with functional parameters. However, RNFL values did not show any significant correlation with any of the functional parameters. Baseline GCL-IPL and optic disc height values had a moderate and significant correlation with final functional parameters. However, RNFL did not show any correlation with final functional parameters. Correlation between GCL-IPL thickness at 6 weeks and final functional parameters were stronger than that with baseline GCL values. Conclusion: In the setting of severe papilledema, RNFL can misguide the prognosis. GCL-IPL can be a valuable tool for an objective evaluation of the integrity of the optic nerve in IIH and ODH may be used as an alternative or in combination with GCL-IPL in these cases.

Relationship between location of epileptic focus and occurrence during sleep versus wakefulness.

Different sleep stages exert differential effects on interictal discharges, neural synchrony and seizure threshold. We sought to assess the relationship between localization of the epileptogenic focus and seizure distribution in sleep versus wakefulness among patients with refractory epilepsy. We conducted a retrospective chart review-based study. Video-electroencephalography of patients with refractory epilepsy, planned for resective surgery, were reviewed for seizure localisation and occurrence relative to stage of sleep/wakefulness. Demographic/clinical data, including details of surgery, were also recorded. Bivariate analysis was conducted using the chi-square test for proportions and unpaired t-test/ANOVA to compare the means within groups. We enrolled 175 patients (107 males) with a mean age of 26.1 + 9.8 years (range: 4-53 years). We analysed 1,282 seizures, of which 916 (71.5%) were temporal, 95 (7.4%) frontal, 144 (11.2 %) central/ parietal and 19 (1.5%) arose from the occipital lobe. Temporal lobe onset seizures were more frequent during wakefulness (77.7%) compared to extra-temporal localization (65%) (p<0.0001). Amongst temporal lobe onset seizures, those during wakefulness arose more frequently from the lateral temporal (88.6%) compared to the mesial temporal lobe (75.5%) (p=0.0003). A higher proportion of seizures evolved into secondary generalisation during sleep (23.5%) versus 8.7% during wakefulness (p<0.0001). Our study demonstrates that lobar location of epileptogenic foci is associated with a predilection of seizures to occur, as well as secondarily generalise, during sleep/wakefulness. Seizures with lateral temporal lobe as well as extratemporal lobe onset were more likely to occur during wakefulness. Overall, sleep related seizures were more likely to be of extratemporal lobe onset, though.

Enoxaparin-induced Wunderlich syndrome in a young patient with anti-GAD 65-associated opsoclonus and limbic encephalitis: a rare complication in a rare disease.

Wunderlich syndrome is a rare condition characterised by acute spontaneous non-traumatic renal haemorrhage into the subcapsular and perirenal spaces. Our case of anti-GAD65-associated autoimmune encephalitis (AE), aged 30 years, developed this complication following use of enoxaparin and was managed by selective glue embolisation of subsegmental branches of right renal cortical arteries. Our case had opsoclonus as one of the clinical manifestations, which has till now been described in only two patients of this AE. This patient received all forms of induction therapies (steroids, plasmapheresis, intravenous immunoglobulin and rituximab) following which she had good improvement in her clinical condition. The good response to immunotherapy is also a point of discussion as this has been rarely associated with anti-GAD65 AE.

Multiple Neurologic Deficits and Cognitive Decline in a Young Woman.

We present the clinicopathologic conference of a 34-year-old lady with history of facial palsy 14 years ago who developed new deficits of mononeuritis multiplex, maculopapular rash, pancytopenia, splenomegaly, lung involvement and cognitive decline rapidly over three years. Investigations revealed pancytopenia, reversal of albumin globulin ratio, mediastinal adenopathy, ANA positivity, low C3 levels with the CSF being inflammatory and MRI showing extensive hemorrhagic lesions with mass effect. She had a rapidly progressive fatal course over three years with the disease being undiagnosed. This case was presented in the annual meeting of the Indian Academy of Neurology in September 2018.

Association between Tumor Necrosis Factor-α (-238G/A and -308G/A) Gene Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis.

Tumor necrosis factor-α (TNF-α) is a proinflammatory pleiotropic cytokine which may contribute to the initiation and progression of ischemic stroke (IS). Thus far, numerous studies have been performed to examine the association between -238G/A (rs361525) and -308G/A (rs1800629) polymorphisms in the promoter regions of the TNF-α gene and susceptibility to IS, but results are still conflicting. The aim of this meta-analysis is to provide a relatively comprehensive account of the association between TNF-α -238G/A and -308G/A gene polymorphisms and susceptibility to IS. A literature search for eligible candidate gene studies published before April 20, 2015, was conducted in the PubMed, Medline, EMBASE and Google Scholar databases. The following combinations of main keywords were used: ('Tumor Necrosis Factor-Alpha' or 'TNF-α') and ('ischemic stroke' or 'cerebral infarction' or 'IS') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Fixed- or random-effect models were used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was carried out by using RevMan 5.3 software. For TNF-α -238G/A gene polymorphism, 7 case-control studies with a total of 1,846 IS patients and 1,905 controls showed a significant association with susceptibility to IS under a dominant model (AA + GA vs. GG; OR, 1.40; 95% CI, 1.11-1.76; p value 0.004). For TNF-α -308G/A gene polymorphism, 16 case-control studies with a total of 5,651 IS patients and 5,792 controls showed a significant protective association with susceptibility to IS under a dominant model (AA + GA vs. GG; OR, 0.78, 95% CI, 0.63-0.97; p value 0.03). Our meta-analysis shows that TNF-α -238G/A gene polymorphism is more likely to be associated with the risk of IS in Caucasian populations as compared to Asian populations. However, TNF-α -308G/A gene polymorphism is more likely to be protective against IS in Asian populations as compared to Caucasian populations. Further large, well-designed prospective epidemiological studies are needed to confirm these findings.

Autologous hematopoietic stem cell transplantation in progressive severe multiple sclerosis.

UNLABELLED: Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS), which is disabling and majorly involves younger population. Various available treatments in forms of immunomodulation are not very effective; however, stem cell transplantation seems to be promising in recent literature. The current case report is a novel evidence for autologous hematopoietic stem cell transplantation (HSCT) in progressive MS. CASE SUMMARY: A 33 year old male with secondary progressive MS (SPMS), after being failed and/or intolerance to standard approved interferon (IFN) and mitoxantrone therapy, autologous HSCT was administered. At 2years of post-stem cell transplantation follow-up, he has remained stable with some improvement in functional status (Expanded Disability Status Scale (EDSS) reduced by 1.5), with no relapse, no treatment related complications, and no fresh magnetic resonance imaging (MRI) lesions. CONCLUSION: Autologous stem cell transplantation may be beneficial in progressive forms of MS, but needs to be tested in well-designed randomized trial.

Autoimmune encephalitis: A potentially reversible cause of status epilepticus, epilepsy, and cognitive decline.

OBJECTIVES: To review clinical characteristics and response to immunomodulation therapy in autoimmune encephalitis presenting with status epilepticus (SE), epilepsy, and cognitive decline. DESIGN: Observational, prospective case series. SETTING: All India Institute of Medical Sciences, New Delhi, India. MATERIALS AND METHODS: Prospective analysis of 15 patients, who presented with SE, epilepsy, cognitive decline, and other neurological symptoms with positive autoantibodies. Demographic and clinical characteristics were recorded. Brain magnetic resonance imaging (MRI), cerebrospinal-fluid analysis (CSF), and tumor screening were done periodically. Treatment received and responses (categorized as per patients and treating doctor's information) were noted. RESULTS: There were 15 (males = 10) patients of autoimmune encephalitis. The mean age of presentation was 24 years (range: 2-64 years). The most common onset was subacute (64%) and four (29%) patients presented as SE. Predominant clinical presentations were seizures (100%) almost of every semiology. CSF was done in 10 patients; it was normal in 60%. Brain MRI was done in all patients, in six (40%) it was normal, six (40%) showed T2W and FLAIR hyperintensities in bilateral limbic areas. Antibodies found were the N-methyl-D-aspartate receptor antibody in seven (50%), voltage-gated potassium channel antibody in five (36%), two of antiglutamic acid decarboxylase, and one patient with double stranded DNA (dsDNA) antibodies. None showed evidence of malignancy. Patients received immunotherapy, either steroids, intravenous immunoglobulin, or both. Follow-up showed significant improvement in majority of cases, neither further seizures nor relapse in nine (67%) cases. One death occurred, due to delayed presentation. CONCLUSIONS: Uncommon but potentially reversible causes of SE, epilepsy, and cognitive decline may be immune-related and high index of suspicion will prevent missing the diagnosis.