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Ajay Kumar Mishra,1 Harshad Arvind Vanjare,2 Anu Anna George,1 Kamal Kant Sahu1 1Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA, USA; 2Department of Radiology, Christian Medical College, Vellore, IndiaCorrespondence: Kamal Kant SahuDepartment of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, USAEmail drkksahu85@gmail.comAbstract: Individuals presenting with sudden and focal neurological findings are usually suspected to have stroke. However, there are other conditions that can simulate stroke, which are often referred to as stroke mimics. Awareness and understanding these stroke-like disorders are of extreme importance as the treatment of each of them might be variable. We hereby briefly discuss these stroke mimics, common differentials, and key features to differentiate amongst the various causes of acute neurological event. Stroke is one of the neurological emergencies that needs urgent intervention to prevent significant mortality and morbidity. At the same time, it is important to realize the importance of other conditions which may mimic to stroke. In this letter, we aim to discuss a few key features that could probably help to distinguish stroke from mimickers thereby helping emergency doctors, neurologists, and hospitalists in streamlining the correct treatment at the earliest.Keywords: COVID-19, stroke, virus, SARS-CoV-2, neurology

Background: Tuberculous meningitis (TBM) remains common in developing countries. Cerebrovascular infarct (CI) in TBM occurs in 15%–57% of patients. Literature regarding the predictors of central nervous system (CNS) infarct in patients with TBM is scanty, and the outcome of these events is unknown. The aim of this study is to evaluate the predictors of CI among patients with TBM at a tertiary care center in South India and to compare the impact of CI on the prognosis and outcomes in terms of mortality and morbidity. Methods: All patients who were confirmed to have TBM and CNS infarcts/stroke were included in this study retrospectively. Forty-six patients had appropriate imaging, and they were enrolled in the study as cases. Patients without infarct were matched with age and sex as controls. Details of the course of the disease, the extent of CNS involvement, and treatment were compared between the two arms. Results: The mean age of patients with and without infarct was similar. The presence of basal meningeal inflammation, hydrocephalus, focal neurological deficit, and cranial nerve palsy, was higher in patients with infarct. Independent predictors of infarcts in a patient with TBM were Medical Research Council (MRC) staging of II or more, presence of focal neurological deficit, cranial nerve palsy, and presence of hydrocephalus, meningeal enhancement on neuroimaging. Presences of infarcts were independently associated with a higher odds ratio of 2.58 for poor outcome, 4.48 for a longer duration of hospital stay, and odds ratio of 8.85 for the requirement of multiple hospitalizations. Conclusion: CI involvement in TBM has higher morbidity, with longer stay, recurrent admission

Background: Invasive fungal disease (IFD) is a sinister complication encountered in patients with haematological disorders. When occurring in the central nervous system (CNS), IFDs can have catastrophic outcomes., Objectives: To study the clinical presentation, predisposing etiological factors, and prognosis of a CNS-IFD in a patient with a haematological disorder., Patients and Methods: This is a retrospective study focusing on the clinical profile, diagnosis, treatment strategy and outcomes of 43 patients with an underlying haematological disorder, who were diagnosed with CNS-IFD between 2018 and 2022., Results: Of the 43 patients, 18 were chemotherapy recipients, while 23 were stem cell transplant (SCT) recipients and 2 presented with CNS-IFD at diagnosis. AML/MDS (37.2%) and ALL (18.6%) were the predominant underlying diagnoses. A sudden deterioration in sensorium (53.5%) was the earliest clinical sign, while T2 hyperintensities (26.8%), vascular involvement (26.8%) and ring-enhancing lesions (16.3%) were the commonest radiological findings, with all patients exhibiting diffusion restriction in diffusion-weighted images. Microbiological evidence of infection was obtained in all patients; however, culture positivity was established in only 25 patients. Rhizopus spp (23.2%) and Aspergillus spp (20.9%) were implicated in most cases. Overall survival of the cohort was 27.9% at a median follow-up of 6 months. In patients who succumbed, the median time to death was 4 days (0-46)., Conclusion: CNS-IFD is associated with very poor survival in patients undergoing chemotherapy or an SCT, urging the need for prompt diagnosis and initiation of suitable antifungal therapy., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Purpose: Basal duct-like recess (DR) sign serves as a specific marker of papillary craniopharyngiomas (PCPs) of the strictly third-ventricular (3 V) topography. Origins of this sign are poorly understood with limited validation in external cohorts., Methods: In this retrospective study, MRIs of pathologically proven PCPs were reviewed and evaluated for tumor topography, DR sign prevalence, and morphological subtypes., Results: Twenty-three cases with 24 MRIs satisfied our inclusion criteria. Median age was 44.5 years with a predominant male distribution (M/F ratio 4.7:1). Overall, strictly 3 V was the commonest tumor topography (8/24, 33.3%), and tumors were most commonly solid-cystic (10/24, 41.7%). The prevalence of DR sign was 21.7% (5/23 cases), all with strictly 3 V topography and with a predominantly solid consistency. The sensitivity, specificity and positive and negative predictive value of the DR sign for strict 3 V topography was 62.5%, 100%, 100% and 84.2% respectively. New pertinent findings associated with the DR sign were observed in our cohort. This included development of the cleft-like variant of DR sign after a 9-year follow-up initially absent at baseline imaging. Additionally, cystic dilatation of the basal tumor cleft at the pituitary stalk-tumor junction and presence of a vascular structure overlapping the DR sign were noted. Relevant mechanisms, hypotheses, and implications were explored., Conclusion: We confirm the DR sign as a highly specific marker of the strictly 3 V topography in PCPs. While embryological and molecular factors remain pertinent in understanding origins of the DR sign, non-embryological mechanisms may play a role in development of the cleft-like variant., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Few treatment options exist for patients with severe central nervous system (CNS) tuberculosis (TB) worsening due to inflammatory lesions, despite optimal antitubercular therapy (ATT) and steroids. Data regarding the efficacy and safety of infliximab in these patients are sparse., Methods: We performed a matched retrospective cohort study based on Medical Research Council (MRC) grading system and modified Rankin Scale (mRS) scores comparing 2 groups of adults with CNS TB. Cohort A received at least 1 dose of infliximab after optimal ATT and steroids between March 2019 and July 2022. Cohort B received only ATT and steroids. Disability-free survival (mRS score ≤2) at 6 months was the primary outcome., Results: Baseline MRC grades and mRS scores were similar between the cohorts. Median duration before initiation of infliximab therapy from start of ATT and steroids was 6 (IQR: 3.7-13) months and for neurological deficits was 4 (IQR: 2-6.2) months. Indications for infliximab were symptomatic tuberculomas (20/30; 66.7%), spinal cord involvement with paraparesis (8/30; 26.7%), and optochiasmatic arachnoiditis (3/30; 10%), worsening despite adequate ATT and steroids. Severe disability (5/30 [16.7%] and 21/60 [35%]) and all-cause mortality (2/30 [6.7%] and 13/60 [21.7%]) at 6 months were lower in cohort A versus cohort B, respectively. In the combined study population, only exposure to infliximab was positively associated (aRR: 6.2; 95% CI: 2.18-17.83; P = .001) with disability-free survival at 6 months. There were no clear infliximab-related side effects noted., Conclusions: Infliximab may be an effective and safe adjunctive strategy among severely disabled patients with CNS TB not improving despite optimal ATT and steroids. Adequately powered phase 3 clinical trials are required to confirm these early findings., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Tuberculosis involving the spinal cord is associated with high mortality and disabling long-term sequelae. Although tuberculous radiculomyelitis is the most frequent complication, pleomorphic clinical manifestations exist. Diagnosis can be challenging among patients with isolated spinal cord tuberculosis due to diverse clinical and radiological presentations. The principles of management of tuberculosis of the spinal cord are primarily derived from, and dependent upon, trials on tuberculous meningitis (TBM). Although facilitating mycobacterial killing and controlling host inflammatory response within the nervous system remain the primary objectives, several unique features require attention. The paradoxical worsening is more frequent, often with devastating outcomes. The role of anti-inflammatory agents such as steroids in adhesive tuberculous radiculomyelitis remains unclear. Surgical interventions may benefit a small proportion of patients with spinal cord tuberculosis. Currently, the evidence base in the management of spinal cord tuberculosis is limited to uncontrolled small-scale data. Despite the gargantuan burden of tuberculosis, particularly in lower and middle-income countries, large-scale cohesive data are surprisingly sparse. In this review, we highlight the varied clinical and radiological presentations, performance of various diagnostic modalities, summarize data on the efficacy of treatment options, and propose a way forward to improve outcomes in these patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Background: Primary intracranial germ cell tumors (ICGCT) are often diagnosed with tumor markers and imaging, which may avoid the need for a biopsy. An intracranial germ cell tumor with mild elevation of markers is seldom stratified as a distinct entity. Methods: Fifty-nine patients were stratified into three groups: pure germinoma (PG), secreting germinoma (SG) and non-germinomatous germ cell tumors (NGGCTs). Results: At 5 years, progression-free survival and overall survival of the three groups (PG vs SG vs NGGCT) were 91% versus 81% versus 59%, and 100% versus 82% versus 68%, respectively. There was no statistically significant difference in outcome among histologically and clinically diagnosed germinomas. Conclusion: A criterion for clinical diagnosis when a biopsy is not feasible is elucidated, and comparable outcomes were demonstrated with histologically diagnosed germinomas.

Temporal lobe epilepsy (TLE) is the most prevalent form of human epilepsy, often accompanied by neurodegeneration in the hippocampus. Like other neurological diseases, TLE is expected to disrupt lipid homeostasis. However, the lipid architecture of the human TLE brain is relatively understudied, and the molecular mechanism of epileptogenesis is poorly understood. We performed desorption electrospray ionization mass spectrometry imaging of 39 fresh frozen surgical specimens of the human hippocampus to investigate lipid profiles in TLE with hippocampal sclerosis ( n = 14) and control (non-TLE; n = 25) groups. In contrast to several previous studies on animal models of epilepsy, we report reduced expression of various important lipids, notably phosphatidylcholine (PC) and phosphatidylethanolamine (PE), in the human TLE hippocampus. In addition, metabolic pathway analysis suggested the possible dysregulation of the Kennedy pathway in TLE, resulting in striking reductions of PC and PE levels. This revelation opens up opportunities to further investigate the associated molecular mechanisms and possible therapeutic targets for TLE.

Background: Tuberculous meningitis (TBM) is a global health problem with important complications such as acute infarcts secondary to vasculitis contributing to adverse outcomes. The objective of this study is to assess intracranial vasculitis in patients with TBM, either during their initial diagnosis or during follow-up while on standard antituberculous therapy., Methods: Ten patients with TBM underwent magnetic resonance (MR) based vessel wall imaging (VWI) to identify intracranial vasculitis (five patients during their initial presentation and the other five patients during their follow-up visit)., Results: Vasculitis was seen in 60% of the patients wherein 70% of their intracranial vessels were affected. Acute and chronic infarcts were seen in four and two patients respectively, one of whom had both acute and chronic infarcts. Leptomeningeal enhancement and basal cisternal tuberculomas were frequently seen in patients with vasculitis. Vasculitis was also seen many days after the commencement of the antituberculous therapy thus explaining late-onset infarcts in this disease., Conclusion: Intracranial vasculitis is common in the patient with TBM. MR-based VWI technique has the potential for infarct risk assessment and to help guide the treatment for its possible prevention., Competing Interests: None

Acute necrotizing encephalopathy after an acute febrile illness, although initially described exclusively in the pediatric age group, has been recently shown to have an adult onset as well. In this study, we describe 10 patients (16 years of age or older) with acute necrotizing encephalopathy. In our study, bilateral thalamic involvement with the trilaminar pattern of diffusion restriction on MR imaging was the predominant finding seen in all of the patients reviewed. Ancillary findings of cerebral white matter, brain stem, and cerebellum involvement with sparing of the basal ganglia were also noted. A poorer outcome was observed in patients with a higher degree of thalamic involvement. The cause of an underlying infection was identified in 4 patients (dengue in 3 and influenza in 1). Overall, a sizeable portion of young adults with acute necrotizing encephalopathy have shown a poorer outcome, with dengue being an important underlying trigger in an endemic region., (© 2020 by American Journal of Neuroradiology.)

Purpose: Skull base osteomyelitis (SBO) is difficult to diagnose due to a wide array of clinical presentations. It can be life threatening if not treated promptly. The objective of this study is to identify the various neck spaces involved in skull base osteomyelitis, correlate them with the possible source of infection and identify the related complications., Methods: Eighty nine consecutive either culture proven cases of skull base osteomyelitis, or culture negative cases with inflammation on histopathology responding to antibiotic therapy, presenting at a single non-government hospital in south India between January 2016 and December 2018 were included in this study. Images were reviewed by two radiologists and imaging findings were documented by consensus., Results: Involvement of the parotid space, retromastoid space and (temporomandibular) TM joint was associated with otogenic source of infection (p value < 0.05); while, retropharyngeal/prevertebral involvement was associated with sphenoid and nasopharyngeal sources (p value < 0.05). Complications such as cavernous sinus thrombosis (p value = 0.023) and ICA involvement (p value = 0.014) were more commonly seen with central skull base osteomyelitis. Abscess formation was seen in all three groups of patients without a significant difference between the groups., Conclusion: Imaging plays an important role in determining the possible source of infection by identifying the involved neck spaces and this in turn can guide the clinician to a site for biopsy. Complications related to SBO can also be identified on imaging and can guide appropriate management., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Tuberculosis (TB) is still a significant health problem worldwide. Central nervous system TB amounts to 10% of all cases of TB. Despite advances in the pharmacological management of TB, the overall outcomes remain poor with significant mortality and morbidity. There are no predictors for neurological outcomes in tuberculosis meningitis (TBM). In this study, we aimed to evaluate the role of cerebrospinal fluid (CSF) C-reactive protein (CRP) in predicting mortality and neurological outcome in TBM. Method: In this observational study, all patients with TBM were recruited prospectively over a 12-month duration. Baseline demographic data, laboratory parameters, and Imaging findings were collected. CSF CRP was obtained on the CSF sample collected at the time of diagnosis. Patients were followed up at 3 months to assess neurological status and mortality., Results: Seventy-one patients with TBM were recruited in this study. The overall mortality in this study was 22.5% of patients. The primary composite outcome of mortality and adverse neurological outcome occurred in 40.8%. The CSF CRP levels ranged between 0.1 and 4.8 mg/dl, and the mean CSF CRP level was 1.11 mg/dl. The Relative risk for a patient with high CSF CRP to develop adverse outcome was 1.84 (P = 0.038). CSF CRP was a good predictor of mortality with a relative risk of 2.92 (P = 0.027). Stroke in TBM had a high incidence of 47.9% and a relative risk of 3.42 for an adverse neurological outcome. CSF CRP did not predict the occurrence of stroke. Hydrocephalus and elevated intracranial pressure were good predictors of stroke., Conclusion: TBM is a disease with significant mortality and morbidity. CRP level in the CSF can be measured, but a highly sensitive scale may be needed as the mean values were much lower compared to the serum values. CSF CRP Levels showed significant associations with adverse outcomes and mortality., Competing Interests: None

Akt is one of the most important downstream effectors of phosphatidylinositol 3-kinase/mTOR pathway. Hyperactivation and expression of this pathway are seen in a variety of neurological disorders including human temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Nevertheless, the expression and activation profiles of the Akt isoforms, Akt1, Akt2, and Akt3 and their functional roles in human TLE-HS have not been studied. We examined the protein expression and activation (phosphorylation) patterns of Akt and its isoforms in human hippocampal tissue from TLE and non-TLE patients. A phosphoproteomic approach followed by interactome analysis of each Akt isoform was used to understand protein-protein interactions and their role in TLE-HS pathology. Our results demonstrated activation of the Akt/mTOR pathway as well as activation of Akt downstream substrates like GSK3β, mTOR, and S6 in TLE-HS samples. Akt1 isoform levels were significantly increased in the TLE-HS samples as compared to the non-TLE samples. Most importantly, different isoforms were activated in different TLE-HS samples, Akt2 was activated in three samples, Akt2 and Akt1 were simultaneously activated in one sample and Akt3 was activated in two samples. Our phosphoproteomic screen across six TLE-HS samples identified 183 proteins phosphorylated by Akt isoforms, 29 of these proteins belong to cytoskeletal modification. Also, we were able to identify proteins of several other classes involved in glycolysis, neuronal development, protein folding and excitatory amino acid transport functions as Akt substrates. Taken together, our data offer clues to understand the role of Akt and its isoforms in underlying the pathology of TLE-HS and further, modulation of Akt/mTOR pathway using Akt isoforms specific inhibitors may offer a new therapeutic window for treatment of human TLE-HS., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Purpose: Dengue is a common arboviral disease, which uncommonly involves the brain. There has been a recent surge in dengue cases and dengue-related deaths in tropical countries. The aim of this study was to describe brain imaging findings in patients with dengue infection having neurologic symptoms., Materials and Methods: Thirty-five patients with positive serology for dengue with CNS symptoms undergoing imaging of the brain were included in the study. Clinical, laboratory, and imaging parameters were assessed and correlated to poor outcome., Results: A Glasgow Coma Scale score of ≤12 at presentation, clinical classification of severe-type dengue, and the presence of acute renal failure were associated with poor outcome. Imaging parameters associated with poor outcome were involvement of the thalami and cerebellar peduncles and the presence of diffusion restriction and hemorrhagic foci in the brain parenchyma., Conclusions: Although not specific, dengue infection has imaging findings that can be used to narrow down the differential list and help in prognostication., (© 2018 by American Journal of Neuroradiology.)

Competing Interests: There are no conflicts of interest.

Competing Interests: There are no conflicts of interest.

Background: Depression in the elderly is a common and disabling condition. The aim of the study was to evaluate the sensitivity and specificity of a two-question screen to identify depression and common mental disorders in the elderly., Method: Residents of a ward in the town of Vellore were identified by a door-to-door survey from which 204 subjects aged over 60 years were selected for the study by systematic random sampling. They were screened using the two-question screen. The Revised Clinical Interview Schedule (CIS-R) was employed to confirm the diagnosis., Results: The prevalence of depression and common mental disorder, using the CIS-R standard, was found to be 31.5%. The two-question screen has a sensitivity of 93.8% and specificity of 48.2%., Conclusions: The high sensitivity of the two-question screen makes it a useful screening method which can be employed by health workers in the field.