Raman Mohan Sharma, Nupur Pruthi, Arivazhagan Arimappamagan, Sampath Somanna, Bhagavathula Indira Devi and Paritosh Pandey
Hydrocephalus is one of the commonest complications of tubercular meningitis (TBM), and its incidence is increasing with the HIV epidemic. Literature evaluating the role of ventriculoperitoneal shunts in HIV-positive patients with TBM and their long-term prognosis is scarce.
Between June 2002 and October 2012, 30 HIV-positive patients with TBM and hydrocephalus underwent ventriculoperitoneal shunt placement. Thirty age-, sex-, and grade-matched HIV-negative patients with TBM and hydrocephalus were randomly selected as the control group. Outcome was analyzed at discharge (short-term outcome) and at follow-up (long-term outcome). Univariate and multivariate analyses were performed to look for predictors of outcome; p < 0.05 was considered significant.
There were no differences in the clinical, radiological, or biochemical parameters between the 2 groups. Short-term outcome was better in the HIV-negative group (76.7% improvement) than in the HIV-positive group (70%). However, the long-term outcome in HIV-positive patients was very poor (66.7% mortality and 76.2% poor outcome) compared with HIV-negative patients (30.8% mortality and 34.6% poor outcome). Seropositivity for HIV is an independent predictor of poor outcome both in univariate and multivariate analyses (p = 0.038). However, in contrast to previous reports, of 5 patients with TBM in good Palur grades among the HIV-positive patients, 4 (80%) had good outcome following shunt placement.
The authors recommend that shunt treatment should not be performed in HIV-positive patients in poor Palur grade with hydrocephalus. A trial of external ventricular drainage should be undertaken in such patients, and shunt treatment should be performed only if there is any improvement. However, HIV-positive patients in good Palur grades should undergo VP shunt placement, as these patients have better outcomes than previously reported.
Subhas Konar, Dhaval Gohil, Dhaval Shukla, Nishanth Sadashiva, Alok Uppar, Dhananjaya I. Bhat, Dwarkanath Srinivas, Arivazhagan Arimappamagan and Bhagavatula Indira Devi
The aim of this study was to report the etiology, clinical features, microbiology, surgical outcome, and predictors of outcome of spontaneous subdural empyema (SDE).
The authors conducted a retrospective study in a tertiary hospital. Children up to 18 years of age, with a diagnosis of SDE with infective etiology, were included in the present cohort. Patients with posttraumatic, postsurgery, and tubercular origin of SDE were excluded from the study. The Glasgow Outcome Scale was used for outcome assessment at the end of 3 months. For analysis purposes, the demographic data, clinical features, radiological data, microbiology, type of surgery, and complication data were categorized, and univariate and multivariable logistic regression analyses were performed to identify the factors associated with outcome.
Ninety-eight children were included in the study and the mean age was 10.9 years. Otogenic origin (34.7%) was the most common source of infection, followed by meningitis (14.3%). The mean duration of symptoms was 12 days. Seventy-six children presented with Glasgow Coma Scale (GCS) score > 8 and the supratentorial location was the most common location. Almost 75% of the children underwent craniotomy or craniectomy and the rest had burr-hole evacuation. Beta-hemolytic Streptococcus (10%) was the most common organism isolated. Cerebral venous thrombosis (CVT; 10.2%) was the most frequent complication in this cohort. The other complications were infarction (6.1%), new-onset seizure (4.1%), and bone flap osteomyelitis (4.1%). Thirteen cases had a recurrence of pus collection, which was more common in the craniotomy group than in the burr-hole group. Age (p = 0.02), GCS score ≤ 8 (OR 8.15, p = 0.001), CVT (OR 15.17, p = 0.001), and presence of infarction (OR 7, p = 0.05) were strongly associated with unfavorable outcome. In multivariable logistic regression analysis, only GCS score ≤ 8 (p = 0.01), CVT (p = 0.02), and presence of infarction (p = 0.04) had a significant impact on unfavorable outcome.
Prompt diagnosis and immediate intervention is the goal of management of SDE, especially in children as a delay in diagnosis can result in unconsciousness and secondary complications such as CVT and infarction, which adversely affect outcome.
Balaram Thota, Arivazhagan Arimappamagan, Thennarasu Kandavel, Arun H. Shastry, Paritosh Pandey, Bangalore Ashwathnarayanarao Chandramouli, Alangar Sathyaranjandas Hegde, Paturu Kondaiah and Vani Santosh
Insulin-like growth factor binding proteins (IGFBPs) have been implicated in the pathogenesis of glioma. In a previous study the authors demonstrated that IGFBP-3 is a novel glioblastoma biomarker associated with poor survival. Since signal transducer and activator of transcription 1 (STAT-1) has been shown to be regulated by IGFBP-3 during chondrogenesis and is a prosurvival and radioresistant molecule in different tumors, the aim in the present study was to explore the functional significance of IGFBP-3 in malignant glioma cells, to determine if STAT-1 is indeed regulated by IGFBP-3, and to study the potential of STAT-1 as a biomarker in glioblastoma.
The functional significance of IGFBP-3 was investigated using the short hairpin (sh)RNA gene knockdown approach on U251MG cells. STAT-1 regulation by IGFBP-3 was tested on U251MG and U87MG cells by shRNA gene knockdown and exogenous treatment with recombinant IGFBP-3 protein. Subsequently, the expression of STAT-1 was analyzed with real-time reverse transcription–polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) in glioblastoma and control brain tissues. Survival analyses were done on a uniformly treated prospective cohort of adults with newly diagnosed glioblastoma (136 patients) using Kaplan-Meier and Cox regression models.
IGFBP-3 knockdown significantly impaired proliferation, motility, migration, and invasive capacity of U251MG cells in vitro (p < 0.005). Exogenous overexpression of IGFBP-3 in U251MG and U87MG cells demonstrated STAT-1 regulation. The mean transcript levels (by real-time RT-PCR) and the mean labeling index of STAT-1 (by IHC) were significantly higher in glioblastoma than in control brain tissues (p = 0.0239 and p < 0.001, respectively). Multivariate survival analysis revealed that STAT-1 protein expression (HR 1.015, p = 0.033, 95% CI 1.001–1.029) along with patient age (HR 1.025, p = 0.005, 95% CI 1.008–1.042) were significant predictors of shorter survival in patients with glioblastoma.
IGFBP-3 influences tumor cell proliferation, migration, and invasion and regulates STAT-1 expression in malignant glioma cells. STAT-1 is overexpressed in human glioblastoma tissues and emerges as a novel prognostic biomarker.
Ajit Mishra, Andiperumal Raj Prabhuraj, Dhaval P. Shukla, Bevinahalli N. Nandeesh, Nagarathna Chandrashekar, Arvinda Ramalingaiah, Arimappamagan Arivazhagan, Dhananjaya Ishwar Bhat, Sampath Somanna and Bhagavatula Indira Devi
Intracranial fungal granuloma (IFG) remains an uncommon entity. The authors report a single-institute study of 90 cases of IFG, which is the largest study until now.
In this retrospective study, all cases of IFG surgically treated in the years 2001–2018 were included. Data were obtained from the medical records and the pathology, microbiology, and radiology departments. All relevant clinical data, imaging characteristics, surgical procedure performed, perioperative findings, and follow-up data were recorded from the case files. Telephonic follow-up was also performed for a few patients to find out their current status.
A total of 90 cases consisting of 64 males (71.1%) and 26 (28.9%) females were evaluated. The mean patient age was 40.2 years (range 1–79 years). Headache (54 patients) was the most common presenting complaint, followed by visual symptoms (35 patients), fever (21 patients), and others such as limb weakness (13 patients) or seizure (9 patients). Cranial nerve involvement was the most common sign (47 patients), followed by motor deficit (22 patients) and papilledema (7 patients). The mean duration of symptoms before presentation was 6.4 months (range 0.06–48 months). Thirty patients (33.3%) had predisposing factors like diabetes mellitus, tuberculosis, or other immunocompromised status. A pure intracranial location of the IFG was seen in 49 cases (54.4%), whereas rhinocerebral or paranasal sinus involvement was seen in 41 cases (45.6%). Open surgery, that is, craniotomy and decompression, was performed in 55 cases, endoscopic biopsy was done in 30 cases, and stereotactic biopsy was performed in 5 cases. Aspergilloma (43 patients) was the most common fungal mass, followed by zygomycosis (13 patients), chromomycosis (9 patients), cryptococcoma (7 patients), mucormycosis (5 patients), and candida infection (1 patient). In 12 cases, the exact fungal phenotype could not be identified. Follow-up was available for 69/90 patients (76.7%). The mean duration of the follow-up was 37.97 months (range 3–144 months). The mortality rate was 52.2% (36/69 patients) among the patients with available follow-up.
A high index of suspicion for IFG should exist for patients with an immunocompromised status and diabetic patients with rhinocerebral mass lesions. Early diagnosis, aggressive surgical decompression, and a course of promptly initiated antifungal therapy are associated with a better prognosis.