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.

Reinfection of COVID-19 among doctors at a tertiary care centre in Northern India: A report from a resource-limited setting.

Background and Aims: There is an increasing recognition of reinfection in coronavirus disease 2019 (COVID-19). We studied the reinfection of COVID-19 disease among doctors at a tertiary care centre in Northern India. Methods: All COVID-19 patients readmitted for COVID-19 disease after any duration with at least a positive Real time- polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 were included. Their clinical profile, vaccination status, outcome and Centre for disease control (CDC), Atlanta, USA reinfection criteria screening were recorded. Results: A total of 57 (0.53%) doctors were identified and 56 of them satisfied the CDC criteria. It included 13 (20.3%) females and 89.3% of cases were from clinical specialities; 98.2% of individuals had the first infection in 2020 and mean duration between 2 infections was 156.29 ± 76.02 (35-298) days. Duration between two episodes of the disease with more than 90 days apart was in 80.3% cases. One (1.8%) patient developed severe disease and two (3.6%) cases were of moderate severity. Symptoms were similar in both infections except significantly higher number of extra-respiratory complaints (2.2% vs. 9.1%). There were 37.5% cases who had received first dose of vaccination of any duration at the time of second infection. Nine (16.1%) and four (7.1%) patients with more than 4 weeks after the first and second dose of vaccination developed the second infection, respectively. Conclusion: Majority of reinfection were symptomatic and developed after 90 days and so majority followed CDC criteria. Breakthrough infections among vaccinated healthcare worker are real, and with sustained exposure to the virus, they should continue to use precaution including hand hygiene and mask in order to prevent reinfection.

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.

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.

A case of ischemic stroke and transient thrombocytopenia in a young female following adenoviral vector-based COVID-19 vaccination: Was the association incidental or causal?

Since March 2021, cases with unusual clots, particularly cerebral venous sinus thrombosis and splanchnic vein thrombosis, have been reported worldwide following adenoviral vector-based coronavirus disease 2019 (COVID-19) vaccination. This entity has been termed vaccine-induced thrombotic thrombocytopenia (VITT). We report a 23-year-old healthy female who developed seizures, altered sensorium, and left hemiparesis, 20 days after receiving the first dose of adenoviral vector-based COVID-19 vaccine "Covishield™." The patient had transient thrombocytopenia. The D-dimer level was 2460 ng/mL. Magnetic resonance imaging (MRI) demonstrated occlusion of M2 segment of the middle cerebral artery and cerebral infarction. Platelet factor-4 antibodies level was normal. Treatment with aspirin and antiepileptic drugs resulted in a remarkable recovery. This is the first Indian case report of ischemic stroke and transient thrombocytopenia following SARS-CoV-2 ChAdOx1 nCoV-19 vaccination. Our case had clinical features consistent with the diagnosis of probable VITT. Familiarity with VITT is crucial because timely treatment with non-heparin anticoagulants and intravenous immunoglobulin improves the outcome.

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.

Metastases from renal cell carcinoma-Report of three unpredictable cases and literature review.

The capacity to metastasize after long periods of discovery and resection of the primary renal lesion or to present as metastasis with undisclosed primary lesions grant renal cell carcinomas (RCC) a formidable and unpredictable behavior. We report three unusual cases of metastasis from RCC. The first patient presented with metastatic clear cell adenocarcinoma in the right shoulder muscles, with unknown primary and revealed an undetected clear cell right RCC on radiology. The second patient presented with a hemorrhagic nasal metastasis of RCC. A history of nephrectomy for RCC, 10 years prior to the development of nasal metastasis was elicited. The third patient presented with axillary and later abdominal wall metastasis of papillary RCC. He had a history of RCC 3 years prior to the discovery of metastasis. RCC has the propensity to appear as a metastatic carcinoma with unknown primary, requiring exclusion of several diagnostic pathologic entities. The appearance of metastasis many years after disease quiescence is challenging and clinicians need to be sensitized to the need for long-term surveillance in RCC. Though the prognosis remains poor, immune checkpoint inhibitors are currently the modalities of choice in such cases.

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.

Predictors of Seizure Recurrence in Solitary Calcified Neurocysticercosis in Relation to Computed Tomography Scan: Prospective Observational Study.

BACKGROUND AND PURPOSE: Solitary calcified neurocysticercosis (NCC) on the computed tomography (CT) scan of brain in patients of epilepsy is common finding in endemic regions. Factors causing seizures in such cases are debatable. Immature calcification may be the causative factor for seizure recurrence. Thus, we aimed to study predictors of seizure recurrence specific to morphological characteristics on CT scan. METHODS: Patients with solitary calcified NCC on CT scan brain and active seizures were prospectively included. The protocol included clinical evaluation, contrast-enhanced CT scan of the brain, and electroencephalogram (EEG) at baseline and 9th month of 1-year follow-up in all patients. Seizure recurrence after 1 week of enrolment was recorded. RESULTS: One hundred twenty patients with a mean age of 23.33±12.81 years were included with a final follow-up of 109 patients and 35 patients had seizure recurrence. On univariate analysis, seizure frequency of more than 1 episode/month (45.7% vs. 25.7%, p=0.037; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.05-5.68), perilesional edema on CT head (45% vs. 10.8%, p<0.001; OR, 6.95; 95% CI, 2.58-18.7), lower density (HU) of lesion on CT head (139.85±76.54 vs. 204.67±135.9 HU p=0.009) and abnormal EEG at presentation (p<0.001; OR, 18.25; 95% CI, 2.15-155.13) were significantly associated with seizure recurrence. On multivariate analysis, presence of perilesional edema on CT head (p=0.001; OR, 6.854; 95% CI, 2.26-20.77), density of lesion on CT (HU) (p=0.036; OR, 0.995; 95% CI, 0.99-1) and abnormal EEG (p=0.029; OR, 12.125; 95% CI, 1.29-113.74) were independently associated with seizure recurrence. CONCLUSIONS: The presence of perilesional edema, HU of calcification on CT brain, and abnormal EEG suggest an increased risk of seizure recurrence in patients of epilepsy with solitary calcified NCC.

Mediastinal Widening in a Patient with Paraplegia: An Unusual Cause.

The common causes of mediastinal widening are lymphadenopathy, pericardial effusion, paravertebral abscess, and aortic aneurysm. We present a patient with spinal tuberculosis, paravertebral abscess, and plural effusion that led to mediastinal widening. In this patient, Chest X-ray was deceptive.

Pathological, ultrasonographic, and electrophysiological characterization of clinically diagnosed cases of pure neuritic leprosy.

A subset of neuritic form of leprosy, called pure neuritic leprosy (PNL), seen in a minority of leprosy patients, is characterized by peripheral neuropathy without skin lesions and an absence of acid-fast bacilli on skin smears. Patients with PNL are often started on drug therapy without confirmation of diagnosis. We, therefore, did a prospective study of clinically diagnosed PNL patients with correlation of ultrasonographic and biopsy findings. A total of 100 consecutive patients with PNL, diagnosed according to the consensus case definition, were included in the study. All patients underwent nerve conduction study, peripheral nerve ultrasonography, and sural nerve biopsy. Multiple mononeuropathies were present in 75% of cases, mononeuropathy in 18%, and polyneuropathy in the remaining 7%. Compared to clinical examination, ultrasonographic assessment of the peripheral nerves was not only better at the detection of thickening but also helped in characterization of their fascicular architecture, echogenicity, and vascularity. A total of 32 cases were confirmed on nerve biopsy, out of which 75% had demonstrable lepra bacilli. Cranial nerve involvement, presence of trophic ulcers, and bilateral thickening of the great auricular nerve were significantly associated with the positivity of lepra bacilli. A significant improvement in the disability score happened after multidrug therapy. A comprehensive electrophysiologic, ultrasonographic, and histological evaluation may be helpful in establishing a diagnosis of PNL with greater confidence, while ruling out other non-leprosy diagnoses.

The spectrum of malignancies presenting with neurological manifestations: A prospective observational study.

INTRODUCTION: A neurological consultation is needed in nearly 45% of patients suffering from cancer. The present study was planned to evaluate the clinical, radiological and histopathological spectrum of patients with an underlying malignancy and presenting with a neurological complaint. MATERIALS AND METHODS: We prospectively evaluated all patients provisionally diagnosed either with a primary or secondary malignancy of the brain on the basis of clinical, radiological and/or histopathological features. RESULTS: A total of 155 patients were enrolled from a total of 4893 admissions done from January 2015 to July 2016. The common presenting symptoms were headache, back pain and paraparesis. Around 26% of patients presented with an altered sensorium, 19.4% with seizures and 21% had at least one cranial nerve involvement. The most common site of involvement was the brain noted in 49.7% of patients. Primary malignancies constituted 78 cases (50.7%) while secondary malignancies included 77 cases (49.3%). Magnetic resonance imaging (MRI) revealed 92 (59.4%) intra-axial lesions and 59 (38.1%) extra-axial lesions, with five cases having both. The most common diagnoses were intra-cerebral metastases and glioblastoma (intra-axial), and vertebral metastases and meningioma (extra-axial). Histopathological confirmation was obtained in 59 patients (38.1%) with 12 primary and 47 secondary lesions. Ten (6.45%) patients had an unknown primary with secondary metastases. The three most common histopathologically confirmed diagnoses were adenocarcinoma lung, plasma cell dyscrasia and adenocarcinoma prostate. CONCLUSION: Primary neurological consultations with an unknown primary are common hence a high index of suspicion can prevent an inadvertent delay in the diagnosis and appropriate treatment of a malignant lesion. Developing a neuro-oncology register may help us in gaining more insight into such situations.