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1.
Neuroradiology ; 66(6): 947-953, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38625616

ABSTRACT

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.


Subject(s)
Craniopharyngioma , Magnetic Resonance Imaging , Pituitary Neoplasms , Sensitivity and Specificity , Humans , Male , Craniopharyngioma/diagnostic imaging , Female , Pituitary Neoplasms/diagnostic imaging , Adult , Middle Aged , Retrospective Studies , Magnetic Resonance Imaging/methods , Aged , Prevalence , Adolescent , Third Ventricle/diagnostic imaging , Third Ventricle/pathology
2.
Clin Infect Dis ; 77(10): 1460-1467, 2023 11 17.
Article in English | MEDLINE | ID: mdl-37405816

ABSTRACT

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.


Subject(s)
Disabled Persons , Infliximab , Tuberculosis, Central Nervous System , Adult , Humans , Antitubercular Agents/adverse effects , Antitubercular Agents/pharmacology , Infliximab/adverse effects , Infliximab/pharmacology , Retrospective Studies , Steroids , Treatment Outcome , Tuberculosis, Central Nervous System/drug therapy
3.
Clin Microbiol Infect ; 29(10): 1298-1305, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37348653

ABSTRACT

OBJECTIVES: To evaluate the efficacy and safety of short-course intravenous amphotericin B followed by sustained release posaconazole tablets for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. METHODS: This prospective, pragmatic study included adults with diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. Patients received short (7-14 days) or long (15-28 days) intravenous antifungal therapy (short intravenous antifungal treatment [SHIFT] or long intravenous antifungal treatment [LIFT], respectively) depending on the presence or absence of brain involvement. All patients received step-down posaconazole tablets, debridement, and glycemic control. The primary outcome was the treatment success at week 14, which was determined by assessing survival and the absence of disease progression through clinical evaluation and nasal endoscopy. Log-binomial regression analysis (risk ratio and 95% CI) was performed to assess factors associated with the primary outcome. RESULTS: Intravenous therapy was administered to 251 participants: SHIFT, 205 (median duration, 13 days); LIFT, 46 (median duration, 22 days). Treatment success at 3 months was 88% (217/248; 95% CI, 83-91%): SHIFT group, 93% (189/203; 89-96%); LIFT group, 62% (28/45; 47-76%). All-cause mortality was 12% (30/251): SHIFT group, 6% (13/205); LIFT group, 37% (17/46). Age (aRR [95% CI]: 1.02 [1.00-1.05]; p 0.027), diabetic ketoacidosis at presentation (2.32 [1.20-4.46]; p 0·012), glycated haemoglobin A1c (1.19 [1.03-1.39]; p 0.019), stroke (3.93 [1.94-7.95]; p 0·0001), and brain involvement (5.67 [3.05-10.54]; p < 0.0001) were independently associated with unsuccessful outcomes. DISCUSSION: Short intravenous amphotericin B with step-down posaconazole tablets should be further studied as primary treatment option for diabetes or COVID-19-associated mucormycosis in randomized controlled trials.


Subject(s)
COVID-19 , Diabetes Mellitus , Mucormycosis , Orbital Diseases , Adult , Humans , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Mucormycosis/complications , Prospective Studies , Orbital Diseases/drug therapy , Orbital Diseases/microbiology , COVID-19/complications , Diabetes Mellitus/drug therapy
4.
Ann Indian Acad Neurol ; 26(2): 112-126, 2023.
Article in English | MEDLINE | ID: mdl-37179681

ABSTRACT

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.

6.
CNS Oncol ; : CNS79, 2021 Nov 22.
Article in English | MEDLINE | ID: mdl-34806399

ABSTRACT

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.


Lay abstract Intracranial germ cell tumors (ICGCTs) are rare brain tumors, which often require markers in blood or cerebrospinal fluid, imaging and a tissue biopsy to establish a diagnosis. However, when tissue sampling is not possible, tumor markers can sometimes be used to diagnose ICGCTs. The authors propose guidelines for a diagnosis and a novel subtype of ICGCT called secreting germinoma, which is also described. Fifty-nine patients were separated into three groups: pure germinoma (PG), secreting germinoma (SG) and non-germinomatous germ cell tumors (NGGCTs). 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 significant difference in outcome among tumors diagnosed with markers in blood or cerebrospinal fluid and those diagnosed with a biopsy. The proposed guidelines for diagnosis need to be evaluated in future studies. SGs may not warrant aggressive treatment protocols as used in NGGCT, and their outcome as a distinct group needs to be explored in future studies.

7.
ACS Chem Neurosci ; 12(21): 4187-4194, 2021 11 03.
Article in English | MEDLINE | ID: mdl-34657435

ABSTRACT

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.


Subject(s)
Epilepsy, Temporal Lobe , Epilepsy , Animals , Epilepsy, Temporal Lobe/diagnostic imaging , Hippocampus , Humans , Lipid Metabolism , Magnetic Resonance Imaging , Mass Spectrometry
8.
Int J Mycobacteriol ; 10(3): 228-233, 2021.
Article in English | MEDLINE | ID: mdl-34494560

ABSTRACT

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.


Subject(s)
Tuberculosis, Meningeal , Vasculitis , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Tuberculosis, Meningeal/diagnosis , Tuberculosis, Meningeal/diagnostic imaging , Vasculitis/diagnostic imaging
9.
J Clin Imaging Sci ; 11: 41, 2021.
Article in English | MEDLINE | ID: mdl-34345531

ABSTRACT

OBJECTIVES: Diffuse infiltrative "non-mass-like" parenchymal lesions on MRI brain are a known presentation of an aggressive condition called lymphomatosis cerebri (LC) but are often misdiagnosed due to its non-specific clinical and imaging findings. We aim to identify clues to differentiate lymphomatosis from its less aggressive mimics based on imaging features. MATERIAL AND METHODS: MRI brain studies showing diffuse infiltrative "non-mass-like" parenchymal lesions between January 2013 and March 2020 were retrospectively identified and read for lesion location, signal characteristics, and enhancement pattern by two radiologists. Additional findings on MRI spine and whole-body fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) were recorded wherever available. The clinical diagnosis, patient demographics, symptoms, laboratory and histopathology results, treatment details, and follow-up details were also noted. RESULTS: Of the 67 patients, 28 (41.7%) were diagnosed with lymphomatosis. The remaining 39 (13.4%) patients were classified as non-lymphomas (infective, vasculitis, and inflammatory conditions). Diffusion restriction on MRI (20/67, P = 0.007) and increased regional activity on FDG PET-CT (12/31, P = 0.017) were the two imaging parameters found to significantly favor lymphomatosis over other conditions, whereas the presence of microhemorrhages on susceptibility-weighted imaging was significantly associated with vasculitis (P = 0.002). Rapid clinical or imaging deterioration on a short trial of steroids (P = 0.00) was the only relevant clinical factor to raise an early alarm of lymphomatosis. Positive serological markers and non-central nervous system systemic diseases were associated with non-lymphomatous diseases. CONCLUSION: LC and its less aggressive mimics can be differentiated on diffusion-weighted imaging-MRI and PET-CT when read in conjunction with rapid progression of clinical features, serological workup, and systemic evaluation.

10.
Int J Infect Dis ; 111: 267-270, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34450284

ABSTRACT

This study was performed to assess the risk factors driving the epidemic of coronavirus disease 2019 (COVID-19)-associated mucormycosis (COVID-Mucor) in India that has accompanied the COVID-19 pandemic, particularly during the second wave. Risk factors were analysed among 164 participants: 132 COVID-Mucor (cases) and 32 non-COVID-Mucor (controls). Data from a prospective cohort study of mucormycosis over a period of 1 year were used. Diabetes mellitus remained a significant risk factor in both groups (97%), while uncontrolled diabetes mellitus (odds ratio (OR) 4.6; P = 0.026) and newly detected diabetes (OR 3.3; P = 0.018) were more common among the cases. Most patients with COVID-Mucor had mild COVID-19. Steroid use, often unwarranted, was highly associated with COVID-Mucor after adjusting for other risk factors (OR 28.4; P = 0.001). Serum ferritin was significantly higher (P = 0.041), while C-reactive protein was not, suggesting that alterations in iron metabolism may predispose to COVID-Mucor. Oxygen was used only in a small minority of patients with COVID-Mucor. The in-hospital mortality in both groups was low. In conclusion, the Indian COVID-Mucor epidemic has likely been driven by a convergence of interlinked risk factors: uncontrolled diabetes mellitus, unwarranted steroid use, and perhaps COVID-19 itself. Appropriate steroid use in patients with severe COVID-19 and screening and optimal control of hyperglycaemia can prevent COVID-Mucor.


Subject(s)
COVID-19 , Mucormycosis , Humans , Mucormycosis/epidemiology , Pandemics , Prospective Studies , Risk Factors , SARS-CoV-2
11.
Acta Neurochir (Wien) ; 163(11): 3143-3154, 2021 11.
Article in English | MEDLINE | ID: mdl-34181087

ABSTRACT

BACKGROUND: Silent corticotroph adenomas (SCAs) are a rare subtype of non-functional pituitary adenoma. While it has been suggested that they are more aggressive and recur more frequently following excision, there is limited literature on the optimum treatment strategy for these tumors, especially regarding the role of radiation therapy in incompletely resected tumors. METHOD: We assimilated data from 62 SCAs and 238 other non-functional adenomas (ONAs), defined according to the WHO 2017 criteria that incorporates transcription factor analysis. We compared their clinicoradiological characteristics, such as hormonal levels, tumor configuration, size, and invasiveness. For 52 SCAs and 205 ONAs with serial follow-up imaging, we studied outcomes for progression after subtotal resection with or without radiation therapy or recurrence after gross total resection. Kaplan Meier analysis for recurrence or progression was used to determine the need for a differential treatment strategy for SCAs compared with other non-functional adenomas specifically concerning the role of radiotherapy. RESULTS: Patients with SCAs present at a younger age than ONAs (43.9 years vs. 48.2 years, p = 0.014), with larger (14.9 cc vs. 9.7 cc, p = 0.006) and more invasive adenomas (61.2% vs. 45.8%, p = 0.021). Overall, SCAs are more likely to recur or progress (48.7 vs. 15.7%, p < 0.001) following excision than ONAs, with significantly poorer event-free survival (Log rank test p < 0.001). Early adjuvant radiotherapy provides favorable outcomes among SCAs with postoperative residual tumor, on par with ONAs. Multivariate analysis identified male gender (HR: 2.217; p = 0.017), MIB index ≥ 3% (HR: 2.116; p = 0.012), and SCA tumor pathology (HR: 3.787; p < 0.001) as factors predicting recurrence. CONCLUSIONS: Based on the results of this retrospective, single-center review of 300 non-functional adenomas, we conclude that silent corticotroph adenomas are an aggressive subtype of non-functional pituitary adenomas that are larger, more likely to be invasive, and tend to recur more frequently after a subtotal excision compared with other non-functional adenomas. A gross total resection must be attempted whenever possible and earlier adjuvant radiation is recommended when re-surgery for residual tumor is difficult.


Subject(s)
ACTH-Secreting Pituitary Adenoma , Pituitary Neoplasms , Transcription Factors , ACTH-Secreting Pituitary Adenoma/diagnostic imaging , ACTH-Secreting Pituitary Adenoma/therapy , Adrenocorticotropic Hormone , Adult , Female , Humans , Male , Middle Aged , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/therapy , Retrospective Studies
12.
Int J Gen Med ; 14: 285-288, 2021.
Article in English | MEDLINE | ID: mdl-33542647

ABSTRACT

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.

13.
14.
Int J Mycobacteriol ; 9(4): 422-428, 2020.
Article in English | MEDLINE | ID: mdl-33323659

ABSTRACT

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.


Subject(s)
C-Reactive Protein , Tuberculosis, Meningeal , C-Reactive Protein/cerebrospinal fluid , Humans
15.
Int J Mycobacteriol ; 9(3): 303-308, 2020.
Article in English | MEDLINE | ID: mdl-32862165

ABSTRACT

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.


Subject(s)
Cerebral Infarction/diagnostic imaging , Tuberculosis, Meningeal/complications , Adult , Aged , Case-Control Studies , Cerebral Infarction/etiology , Cerebral Infarction/mortality , Female , Humans , India , Male , Odds Ratio , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Factors , Tertiary Care Centers
16.
Clin Imaging ; 67: 62-67, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32526659

ABSTRACT

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.


Subject(s)
Osteomyelitis/diagnostic imaging , Skull Base/diagnostic imaging , Anti-Bacterial Agents/therapeutic use , Biopsy/adverse effects , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nasopharynx , Osteomyelitis/diagnosis , Skull Base/pathology
17.
Neurochem Int ; 134: 104654, 2020 03.
Article in English | MEDLINE | ID: mdl-31884041

ABSTRACT

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 GSK3ß, 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.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Epilepsy, Temporal Lobe/metabolism , Hippocampus/metabolism , Sclerosis/metabolism , TOR Serine-Threonine Kinases/metabolism , Cytoskeletal Proteins/metabolism , Cytoskeleton/metabolism , Humans , Isoenzymes/metabolism , Phosphorylation , Sclerosis/pathology
18.
Can J Neurol Sci ; 45(6): 669-674, 2018 11.
Article in English | MEDLINE | ID: mdl-30289088

ABSTRACT

BACKGROUND: Neurological complications following snake and scorpion bite are diverse. Literature regarding patterns of cerebrovascular injury (CVI) and outcomes among these patients is scarce. This is a descriptive study of the clinical profile, brain imaging findings, mechanisms of injury, vascular territory involvement and outcomes of CVI following scorpion and snake envenomation, in a tertiary care center in South India.MethodologyPatients with scorpion sting- and snake envenomation-related complications were retrospectively enrolled. Neuroimaging was performed on five patients with each envenomation, and they were found to have neurological involvement. On imaging, three patients were found to have a CVI. Clinical, radiological parameters and outcomes of these patients were studied. We also performed a review of the literature and analyzed the finding of all the cases.ResultIn all, three patients each had evidence of CVI in imaging. An additional 32 reports of scorpion sting-related CVI and 35 reports of snake envenomation-related CVI were identified from the literature. There was a male predominance among these patients. Mean age of the patients with scorpion sting was 42.8 years as compared with 33 years for the patients with snake envenomation. Features of severe envenomation were present in all patients. Persistently depressed sensorium and new-onset focal neurological deficits were seen in 70% of all patients. Infarcts were seen in 88% of patients with snake envenomation and 53% of patients with a scorpion sting. Mortality was 28% among patients with a scorpion sting as compared with 8% with snake envenomation. CONCLUSION: Cerebrovascular injuries are uncommon neurological manifestations following scorpion and snake envenomation. These tend to occur in younger patients. Infarcts are more common than bleeds.


Subject(s)
Age Factors , Cerebrovascular Disorders/etiology , Scorpion Stings/complications , Snake Bites/complications , Adolescent , Adult , Aged , Animals , Female , Humans , Male , Middle Aged , Neuroimaging , Retrospective Studies , Risk Factors , Scorpions/pathogenicity , Young Adult
19.
Int J Stroke ; 13(1): 57-65, 2018 01.
Article in English | MEDLINE | ID: mdl-28421878

ABSTRACT

Background Cryptococcal meningitis continues to be one of the common causes of chronic central nervous system infection worldwide. Individuals with cryptococcal meningitis can occasionally present with small vessel vasculitis causing infarcts primarily in the basal ganglia, internal capsule, and thalamus. Literature regarding patterns of cerebrovascular injury among patients with cryptococcal meningitis is scanty, and outcome following these vascular involvements is unknown. Aim To study the clinical profile, imaging findings, and details of vascular territory involved among patients admitted with cryptococcal meningitis and central nervous system infarct in a tertiary care center from India. And to compare the outcomes of patients of cryptococcal meningitis with or without central nervous system infarcts in terms of mortality and morbidity, Methodology A total of 151 patients with microbiologically proven cryptococcal meningitis over a time span of 11 years were retrospectively enrolled into the study. Of these, 66 patients met the inclusion criteria of having appropriate imaging of the brain. The presence of infarct in the imaging was analyzed by two independent radiologists. Patterns of central nervous system involvement and types of vascular injury were ascertained based on radiological parameters. Clinical parameters and outcomes of patients with and without infarcts were compared. Results Twenty (13%) of these patients had evidence of central nervous system infarcts on imaging. The mean age of patients with and without infarcts was 41 years and 38 years, respectively. Male predominance was present among both the groups. The presence of fever, neck stiffness, positive blood culture, and hydrocephalus in central nervous system imaging was similar among patients with or without infarct. Longer duration of illness, low sensorium at the time of presentation, low Glasgow Coma Scale score, presence of meningeal inflammation, cryptococcomas, and basal exudates in imaging were higher in patients with infarct. All the infarcts were of the lacunar type. Sixty percent of the cerebrovascular infarcts were acute in nature, 50% of these being multiple. Unilateral infarcts were seen in 70% of the patients. The most common site of infarct was the basal ganglia, others being distributed over the thalamus, frontal, temporal, parieto-occipital regions in the descending order. The presence of neurovascular involvement in the form of infarcts to the risk of morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively. Conclusion Neurovascular involvement in chronic cryptococcal meningitis is a rare entity. These tend to present as multiple lacunar infarcts. Mortality and morbidity associated with these patients is higher when compared to patients who do not have infarcts. This result suggests that vascular injury plays a role in predicting outcome of patients with cryptococcal meningitis. Future studies are needed to understand the mechanism by which vascular events (infarcts) occur and result in poor outcome.


Subject(s)
Cerebral Infarction/epidemiology , Meningitis, Cryptococcal/epidemiology , Adult , Brain/pathology , Case-Control Studies , Cerebral Infarction/diagnostic imaging , Cerebral Infarction/mortality , Comorbidity , Female , Humans , India/epidemiology , Magnetic Resonance Imaging , Male , Meningitis, Cryptococcal/mortality , Neuroimaging , Retrospective Studies , Risk Factors , Young Adult
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