The spectrum of psychiatric manifestations in subacute sclerosing panencephalitis: A systematic review of published case reports and case series.

Data related to psychiatric manifestations in subacute sclerosing panencephalitis (SSPE) is currently available only in the form of isolated case reports. In this systematic review, we evaluated the spectrum of psychiatric manifestations and their impact on the course and outcome of SSPE. Data were obtained from 4 databases (PubMed, Embase, Scopus, and Google Scholar), with the most recent search conducted on March 27, 2023. The PRISMA guidelines were followed, and the PROSPERO registration number for the protocol is CRD42023408227. SSPE was diagnosed using Dyken's criteria. Extracted data were recorded in an Excel spreadsheet. To evaluate the quality of the data, the Joanna Briggs Institute Critical Appraisal tool was employed. Our search resulted in 30 published reports of 32 patients. The mean age was 17.9 years. Schizophrenia, catatonia, and poorly characterized psychotic illnesses were the 3 most common psychiatric presentations that were seen in 63% (20/32) of cases. Catatonia was seen in 4 patients. Affective disorders, mania, and depression were reported among 22% (7/32) cases. In approximately 81% (26/32) cases, the course of SSPE was acute fulminant. Treatment with antipsychotic drugs had poor or no response. Out of 17 patients, who received antipsychotic drugs, 6 patients noted severe extrapyramidal adverse effects. SSPE often masquerades as a psychiatric disorder. Unresponsive psychiatric symptoms, early extrapyramidal signs, and progressive encephalopathy indicate SSPE.

Tumor Necrosis Factor-α, CD1A and CD1E Genetic Polymorphisms in Guillain-Barré Syndrome: A Study from India.

Background: Guillain-Barré Syndrome (GBS) is an acute acquired autoimmune inflammatory disorder of peripheral nerves and roots. The pathogenesis is essentially an aberrant post-infectious immune response in a genetically susceptible host milieu. Single nucleotide polymorphisms (SNP) in genes encoding the inflammatory mediators like TNF-α, CD1A and CD1E can influence their expression and level and the susceptibility and clinical course of disease in GBS. Objective: We tried to study the susceptibility of single nucleotide polymorphisms of TNF-α and CD1 genes in Guillain-Barré Syndrome in Indian population and determine the association in terms of genotype, allele and haplotype distribution along with individual subtype, severity and clinical outcome. Methodology: In this case-control study, we investigated the single nucleotide polymorphism pattern in the promoter region of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E genes using real-time polymerase chain reaction in 75 GBS patients and analysed in comparison with 75 age and sex-matched healthy controls. Results: The findings revealed that the allelic distribution of TNF-α (-308 G/A) *A allele was associated with GBS (P value 0.04, Odds Ratio 2.03, 95% Confidence Interval 1.01-4.07). There was no association found with genotype, haplotype combination and other allele distribution for GBS in the study. CD1A and CD1E SNPs did not reveal any susceptibility for GBS. The subtype analysis did not reveal any statistical significance, except for CD1A *G allele with AMAN subtype (P value 0.026). The haplotypic combinations and mutant allele of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E were significantly associated with severe GBS in the study. However, there was no association of any SNP for mortality and survival of GBS in the study. Conclusion: TNF-α (-308 G/A)*A allele might confer genetic susceptibility for GBS in Indian population. CD1 genetic polymorphism could not be considered for susceptibility to GBS. TNF-α and CD1 genetic polymorphism did not affect mortality in GBS.

Transcriptomics and Proteomics Approach for the Identification of Altered Blood microRNAs and Plasma Proteins in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by the selective destruction of dopaminergic neurons (DA-nergic). Clinically, PD is diagnosed based on developing signs and symptoms. A neurological and physical examination and sometimes medical and family history also help in the diagnosis of PD. However, most of these features are visible when more than 80% of the dopaminergic neurons have degenerated. An understanding of the selective degeneration process at the cellular and molecular level and the development of new biomarkers are required for effective PD management. Several studies have been carried out using a selected set of miRNAs/ mRNAs and proteins to develop biomarkers of PD; however, an unbiased and combined miRNA-protein profiling study was required to identify the markers of progressive and selected degeneration of dopaminergic neurons in PD patients. In the present study, we have carried out global protein profiling through LC-MS/MS and miRNA profiling by using a "brain-specific" miRNA array panel of 112 miRNAs in PD patients and healthy controls to find the unprejudiced group of proteins and miRNAs that are deregulating in PD. In the whole blood samples of PD patients compared to healthy controls, the expression of 23 miRNAs and 289 proteins was significantly increased, whereas the expression of 4 miRNAs and 132 proteins was considerably downregulated. Network analysis, functional enrichment, annotation, and analysis of miRNA-protein interactions were also performed as part of the bioinformatics investigation of the discovered miRNAs and proteins revealing several pathways that lead to PD development and pathogenesis. Based on the analysis of miRNA and protein profiling, we have identified four miRNAs (hsa-miR-186-5p, miR-29b, miR-139 & has-miR-150-5p) and four proteins (YWHAZ, PSMA4, HYOU1, & SERPINA1), which can be targeted for the development of new biomarkers of PD. In vitro studies have identified the role of miR-186-5p in regulating the levels of the YWHAZ/YWHAB & CALM2 gene, which has shown maximum downregulation in PD patients and is known for its role in neuroprotection from apoptotic cell death & calcium regulation. In conclusion, our research has identified a group of miRNA-proteins that can be developed as PD biomarkers; however, future studies on the release of these miRNAs and proteins in extracellular vesicles circulating in the blood of PD patients can further validate these as specific biomarkers of PD.

Immune-dysregulation in subacute sclerosing panencephalitis: An exploratory case-control study.

Subacute sclerosing panencephalitis (SSPE) is a chronic progressive neurological condition caused by a defective measles virus. It is postulated that immune-dysregulation might result in persistent infection (immune evasion) as well as initiation of autoimmune phenomenon (via natural killer cells) leading to panencephalitis. The primary objective of this case-control study was to analyse the pattern of immune dysregulation in cases with SSPE. The secondary objective was to assess the correlation between the measured immunological variables and disability/death at 6 months. This was an exploratory case-control study conducted at a tertiary-care referral-facility from January 2020 to September 2021. Thirty consecutive patients fulfilling the Dyken's criteria for SSPE and 30 age-and-sex-matched healthy controls were enrolled. Immunological profile constituted by lymphocyte subset analysis, immunoglobulin levels and complement levels were done in all cases and controls. Cases were staged as per Jabbour's system; disability was assessed using the modified Rankin Scale (mRS). Patients with SSPE had a mean age of 14.76 years (±6.9 years). There were 25 males and 5 females; 6.7% cases belonged to Jabbour's first stage, 40% to second stage and 53.3% to third stage. At least 1/4th had evidence of measles vaccination. Levels of absolute lymphocyte count, B-cells, T cells, helper T-cells, and cytotoxic T-cells were significantly higher in cases. IgG, IgM, and IgE levels were significantly higher while IgD levels were significantly lower in cases. At baseline, 13.3% of cases had a mRS score of 0-2 and 86.7% had a score of 3-6; at 6 months 10% had a mRS score 0-2 (favorable outcome) while 90% had a mRS score 3-6 (poor outcome). Higher IgE levels were found to correlate significantly with favorable outcome. Immune-dysregulation may play a significant role in shaping one's response to measles infection as well as in determining vaccine-efficacy.

Nerve biopsies in patients with peripheral neuropathy: A prospective evaluation.

Background: In approximately 25% of peripheral neuropathy cases, diagnosis remains obscure. In India, leprosy continues to remain one of the most frequent causes of peripheral neuropathy. We, in this prospective evaluation, performed nerve biopsies in patients with peripheral neuropathy for early confirmation of the diagnosis. Materials and Methods: A total of 55 consecutive cases of peripheral neuropathy were included in this study. All patients were subjected to clinical and electrophysiological evaluation. Sural nerve biopsies were performed in all the patients. Result: After a nerve biopsy in 29 cases, we were able to identify the underlying cause of peripheral neuropathy. In 26 cases, the diagnosis remained obscure. The most frequent histopathological diagnosis was leprosy, which was seen in 20 cases. Other diagnoses were chronic demyelinating neuropathy (four cases), vasculitis (two cases), and amyloidosis in one case. In two biopsies, the findings were consistent with hereditary neuropathies. The demonstration of lepra bacilli was the most distinctive feature. In addition, foamy macrophages (100%) and granuloma (100%) formation, epineurial (83.3%) and endoneurial infiltration (69%) along with epineurial (87.5%) and perineurial thickening (77.3%) were also noted more frequently in leprosy-associated neuropathy. Conclusion: The nerve biopsies revealed that leprosy was the most common etiology in patients with peripheral neuropathy. In approximately 47% of the cases, even nerve biopsies failed to establish a confirmed diagnosis.

A Comprehensive Investigation of the Current Subacute Sclerosing Panencephalitis (SSPE) Treatment Options to Improve Patient Quality of Life.

Subacute sclerosing panencephalitis (SSPE) is a progressive, disabling, and deadly neurological disorder related to measles (rubeola) infection occurring primarily in children. The slow but persistent viral infection occurs in children or young adults and affects their central nervous system (CNS). There have been plenty of reports on SSPE throughout the world, but it is considered a rare disease in developed countries. This research focuses on comparing the current treatments available to prolong the life of patients for over three years after the onset of SSPE. The goal was to identify possible patterns or trends among the treatments in order to find the best possible method to lengthen a patient's life. The results indicated that interferon alpha, inosine pranobex, and ribavirin display the most effective treatment plan and indicate the most potential in discovering a more effective therapeutic for SSPE.

Epidemic of Mucormycosis in COVID-19 Pandemic: A Position Paper.

During the second wave of COVID-19 pandemic, there is a sudden increase in number of cases mucormycosis infection in India. This communication by the Tropical Neurology subsection expert group of the Indian Academy of Neurology (IAN) describes the clinical and diagnostic features, treatment of the disease and gives recommendations about the ways forward.

Tumefactive Demyelinating Brain Lesion Developing after Administration of Adenovector-Based COVID-19 Vaccine: A Case Report.

Background: Postmarketing surveillance of COVID-19 vaccination reveals that the COVID-19 vaccine administration is associated with several rare but serious neurological complications. Case Report: We report a case of new-onset tumefactive demyelinating brain lesion that developed after administration of an adenovector-based COVID-19 vaccine. A middle-aged female presented with recent right hemiparesis, which was noticed 2 days after she received the first dose of the vaccine. Magnetic resonance imaging (MRI) revealed a large subcortical T2/FLAIR hyperintensities involving corpus callosum as well. The patient responded to oral methylprednisolone. At 4 weeks, a follow-up MRI revealed a reduction in size of the lesion. Conclusion: To conclude, adenovector-based COVID-19 vaccination may be associated with a tumefactive demyelinating lesion.

COVID-19-associated Guillain-Barre syndrome: Postinfectious alone or neuroinvasive too?

Coronavirus disease 2019 (COVID-19) has been shown to be associated with a lot of neurological complications, of whom Guillain-Barre syndrome (GBS) is an important post-infectious consequentiality. More than 220 patients with GBS have been reported thus far. We intend to share our experience with five patients of GBS where one of them had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the cerebrospinal fluid (CSF). This is the first-ever report demonstrating the presence of SARS-CoV-2 in the CSF of an adult patient; a similar occurrence has recently been described in a pediatric patient. We wish to emphasize the fact that commonly GBS occurs as a result of a post-infectious process but in a few cases where the symptoms of COVID-19 and GBS occur concurrently, corresponding to the viremic phase, separate pathogenesis needs to be thought of. This para-infectious nature is exemplified by the presence of virus in the cerebrospinal fluid of one of our patients. We review the neuroinvasive potential of SARS-Cov-2 in this regard and draw parallels with Cytomegalovirus, Zika virus, and Human Immunodeficiency virus-associated occurrences of GBS.

Metals toxicity and its correlation with the gene expression in Alzheimer's disease.

Alzheimer's disease is a common neurodegenerative disease in the elderly population and a leading cause of dementia. Genetics and environmental risk factors were considered to play a major role in the onset of the disease. This study aimed to examine the correlation between different metals levels and the gene expression in Alzheimer's patients with age-matched control subjects. Non- essential metals were measured in the whole blood due to its higher concentration in red blood corpuscles (RBCs) and essential biometals in the serum samples of Alzheimer's disease (AD) by using Inductively coupled plasma optical emission spectroscopy (ICP-OES) that allows the analysis and detection of the different elements at low levels. Gene expression level was performed by quantitative real-time PCR (qRT-PCR). In this study, the levels of Lead and Arsenic metals were not detected in the AD patient samples. Cadmium, Mercury, and Aluminum were found higher in cases as compared to controls with 0.009240 ± 0.0007707 (P = < 0.0001), 0.02332 ± 0.001041 (P = < 0.0001), and 0.09222 ± 0.02804 (P = 0.0087) respectively. Essential biometal like copper was higher 0.1274 ± 0.02453 (P = 0.0254) in cases, while iron 0.1117 ± 0.009599 (P = 0.0304) and zinc 0.03800 ± 0.003462 mg/L were found significantly lower as compared to controls. All targeted genes such as APP, PSEN1, PSEN2, and APOE4 were found up-regulated in AD patients. We concluded that there was no significant correlation between metals dyshomeostasis and gene expressions in this study.

Neuroimaging Patterns in Patients with COVID-19-Associated Neurological Complications: A Review.

BACKGROUND: A variety of neuroimaging abnormalities in COVID-19 have been described. OBJECTIVES: In this article, we reviewed the varied neuroimaging patterns in patients with COVID-19-associated neurological complications. METHODS: We searched PubMed, Google Scholar, Scopus and preprint databases (medRxiv and bioRxiv). The search terms we used were "COVID -19 and encephalitis, encephalopathy, neuroimaging or neuroradiology" and "SARS-CoV-2 and encephalitis, encephalopathy, neuroimaging or neuroradiology". RESULTS: Neuroimaging abnormalities are common in old age and patients with comorbidities. Neuroimaging abnormalities are largely vascular in origin. COVID-19-associated coagulopathy results in large vessel occlusion and cerebral venous thrombosis. COVID-19-associated intracerebral hemorrhage resembles anticoagulant associated intracerebral hemorrhage. On neuroimaging, hypoxic-ischemic damage along with hyperimmune reaction against the SARS-COV-2 virus manifests as small vessel disease. Small vessel disease appears as diffuse leukoencephalopathy and widespread microbleeds, and subcortical white matter hyperintensities. Occasionally, gray matter hyperintensity, similar to those observed seen in autoimmune encephalitis, has been noted. In many cases, white matter lesions similar to that in acute disseminated encephalomyelitis have been described. Acute disseminated encephalomyelitis in COVID-19 seems to be a parainfectious event and autoimmune in origin. Many cases of acute necrotizing encephalitis resulting in extensive damage to thalamus and brain stem have been described; cytokine storm has been considered a pathogenic mechanism behind this. None of the neuroimaging abnormalities can provide a clue to the possible pathogenic mechanism. CONCLUSIONS: Periventricular white-matter MR hyperintensity, microbleeds, arterial and venous infarcts, and hemorrhages are apparently distinctive neuroimaging abnormalities in patients with COVID-19.

A deep learning-based COVID-19 automatic diagnostic framework using chest X-ray images.

The lethal novel coronavirus disease 2019 (COVID-19) pandemic is affecting the health of the global population severely, and a huge number of people may have to be screened in the future. There is a need for effective and reliable systems that perform automatic detection and mass screening of COVID-19 as a quick alternative diagnostic option to control its spread. A robust deep learning-based system is proposed to detect the COVID-19 using chest X-ray images. Infected patient's chest X-ray images reveal numerous opacities (denser, confluent, and more profuse) in comparison to healthy lungs images which are used by a deep learning algorithm to generate a model to facilitate an accurate diagnostics for multi-class classification (COVID vs. normal vs. bacterial pneumonia vs. viral pneumonia) and binary classification (COVID-19 vs. non-COVID). COVID-19 positive images have been used for training and model performance assessment from several hospitals of India and also from countries like Australia, Belgium, Canada, China, Egypt, Germany, Iran, Israel, Italy, Korea, Spain, Taiwan, USA, and Vietnam. The data were divided into training, validation and test sets. The average test accuracy of 97.11 ± 2.71% was achieved for multi-class (COVID vs. normal vs. pneumonia) and 99.81% for binary classification (COVID-19 vs. non-COVID). The proposed model performs rapid disease detection in 0.137 s per image in a system equipped with a GPU and can reduce the workload of radiologists by classifying thousands of images on a single click to generate a probabilistic report in real-time.

Hydrocephalus in Tuberculous Meningitis - Pearls and Nuances.

Tuberculous meningitis (TBM) is associated with high mortality. A large proportion of patients with TBM, who survive, live with disabling neurological sequelae. Hydrocephalus is one of the common complications of TBM, seen in up to 80% of patients. Hydrocephalus may be a presenting feature or may develop paradoxically after the commencement of antituberculosis treatment. The Hallmark pathological feature of TBM is a thick gelatinous exudate, dominantly present at basal parts of the brain. Exudate encases and strangulates cranial nerve trunks like optic nerve, optic chiasma, and vessels of the circle of Willis. Basal exudate also blocks the cerebrospinal fluid (CSF) flow in the brain, resulting in ventriculomegaly. It is often difficult to differentiate between two common types (communicating and obstructive) of hydrocephalus on basis of routine neuroimaging. Progressive hydrocephalus, clinically manifests with a potentially life-threatening high intracranial pressure. Patients with deteriorating vision loss and deteriorating consciousness, often need a surgical CSF diversion procedure (ventriculoperitoneal shunt or endoscopic third ventriculostomy) to be performed. CSF diversion may be life-saving. However, the long-term benefits of CSF diversion are largely unknown.