Multiparametric magnetic resonance imaging features of giant intracranial tuberculomas.

OBJECTIVES: To evaluate Magnetic Resonance Imaging (MRI) features of Giant Tuberculomas (GT) of the brain and deduce characteristic imaging phenotypes which may differentiate GT from higher grade glioma. METHODS: A retrospective analysis of MRI was done on Tuberculomas of size >2 cm. The diagnosis was established by histopathology or presumed from size reduction on follow-up MRI while on empirical anti-tubercular therapy (ATT). Multimodality characteristics of GT on T1/T2W, Fluid attenuation recovery (FLAIR), Diffusion-Weighted imaging (DWI), Susceptibility Weighted Imaging (SWI), Spectroscopy (MRS) and Perfusion weighted sequences were assessed. These imaging features were also evaluated in WHO Grade IV, IDH-wild type glioma (histopathologically and genetically proven) and a comparative analysis of the imaging features between GT and glioma was done. RESULTS: Thirty-two GT and 20 glioma were evaluated. Pronounced intralesional T2 hypointensity (n = 8;25%), T2 hyperintense crescent beneath the periphery (n = 25, 78.1%), T2W lamellated/whorled appearance (n = 17;53.125%), hyperintense rim on T1W MT (n = 25;78.1%), peripheral rim of diffusion restriction (n = 22; 68.75%), peripheral rim of blooming on SWI (n = 20, 62.5%), prominent lipid resonance on MR spectroscopy (n = 30; 93.75%), overshoot of the signal intensity-time curve above the base line (n = 9/10; 90%) on dynamic susceptibility contrast (DSC) perfusion, were remarkable imaging characteristics. Reduction of peripheral T1 hyperintensity, compaction of T2 hypointense core, expansion of sub-marginal T2 hyperintense rim and increased peripheral susceptibility (n = 20; 62.5%) during follow-up imaging, while on ATT, were standout features. GT could be differentiated from WHO grade IV (IDH-wild type) glioma on the basis of a significantly higher proportion of GTs showing a whorled/lamellated appearance, T1 hyperintense rim, T2 hypointense core, DWI-ADC mismatch, well-defined rim on SWI, prominent lipid peak on MRS and a submarginal T2 hyperintense rim. GT showed a higher normalized ADC ratio from the core as well as the rim. Significantly higher proportion of glioma showed a T1 hypointense and T2 hyperintense core and a nodular rim enhancement. A significantly higher r CBV, Choline to creatine, choline to NAA ratio and mean thickness of the peripheral enhancing rim were defining features among gliomas. CONCLUSION: Neuroimaging features of GT have been elucidated. Reduction of peripheral T1 hyperintensity, compaction of T2 hypointense core, expansion of sub-marginal T2 hyperintense rim, and increased peripheral susceptibility on follow-up may be considered imaging markers of response to anti-tubercular therapy. Multiparametric MRI features can differentiate GT from WHO grade IV (IDH-wild type) glioma.

Central nervous system infection due to Cryptococcus gattii sensu lato in India: Analysis of clinical features, molecular profile and antifungal susceptibility.

Cryptococcus gattii species complex has evolved as a pathogen in the last two decades causing infection among both immunocompetent and immunocompromised hosts. We aimed to analyse the clinical features of CNS infection caused by C. gattii sensu lato, molecular and antifungal susceptibility profile of this pathogen. Cases diagnosed to have CNS cryptococcosis were included in the study. Cryptococcus recovered from patient's specimen was identified by standard protocol. Species confirmation, mating type and molecular type determination were performed by PCR based methods. Antifungal susceptibility was tested in VITEK2C to amphotericin B, 5-flucytosine, fluconazole and voriconazole. Among 199 cases, 20 (10%) were due to C. gattii, comprising of 75% cryptococcal meningitis and 25% cryptococcoma cases. Young adult males were commonly affected. Headache and vomiting were prominent symptoms and 50% were immunocompromised. Among the isolates, 75%, 20% and 5% were C. tetragattii, C. gattii sensu stricto and C. bacillisporus respectively and all had mating type α. Four (20%) isolates of C. tetragattii and the only isolate of C. bacillisporus were resistant to fluconazole. The most common species isolated from south India is C. tetragattii. The study contributes to the epidemiology of C. gattii and reiterates the need for genotyping and antifungal susceptibility testing.

Hypersomnolence-hyperkinetic movement disorder in a child with compound heterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene.

Deficiency of gamma-amino-butyrate aminotransferase (ABAT) is a rare inherited disorder. A six-month-old girl presented with hyper-somnolence, hyperkinetic movements of distal extremities during wakefulness, hypotonia, bi-pyramidal signs, and impaired response to sound and visual stimuli. Brain MRI at five months showed restricted diffusion along the internal capsule and genu of corpus callosum. A follow up MRI at 18months, showed hyperintensities in brainstem, external and internal capsule, 'trilaminated' appearance of posterior limb of internal capsule and dysmyelination of sub-cortical white matter. MRS showed a peak between 2.2ppm and 2.4ppm, corresponding to glutamine, glutamate and GABA. EEG was normal at six months but showed multifocal epileptiform discharges at 18months. Targeted exome sequencing revealed compound heterozygous missense variations in ABAT resulting in its reduced function. We report the novel association of hypersomnolence and hyperkinetic movement disorder with ABAT variations thus expanding the clinical spectrum of this uncommon neuro-metabolic disorder and discuss the emerging role of GABA in pathways regulating sleep-wake cycle and movement disorders.

Assessment of tissue heterogeneity using diffusion tensor and diffusion kurtosis imaging for grading gliomas.

INTRODUCTION: In this work, we aim to assess the significance of diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) parameters in grading gliomas. METHODS: Retrospective studies were performed on 53 subjects with gliomas belonging to WHO grade II (n = 19), grade III (n = 20) and grade IV (n = 14). Expert marked regions of interest (ROIs) covering the tumour on T2-weighted images. Statistical texture measures such as entropy and busyness calculated over ROIs on diffusion parametric maps were used to assess the tumour heterogeneity. Additionally, we propose a volume heterogeneity index derived from cross correlation (CC) analysis as a tool for grading gliomas. The texture measures were compared between grades by performing the Mann-Whitney test followed by receiver operating characteristic (ROC) analysis for evaluating diagnostic accuracy. RESULTS: Entropy, busyness and volume heterogeneity index for all diffusion parameters except fractional anisotropy and anisotropy of kurtosis showed significant differences between grades. The Mann-Whitney test on mean diffusivity (MD), among DTI parameters, resulted in the highest discriminability with values of P = 0.029 (0.0421) for grade II vs. III and P = 0.0312 (0.0415) for III vs. IV for entropy (busyness). In DKI, mean kurtosis (MK) showed the highest discriminability, P = 0.018 (0.038) for grade II vs. III and P = 0.022 (0.04) for III vs. IV for entropy (busyness). Results of CC analysis illustrate the existence of homogeneity in volume (uniformity across slices) for lower grades, as compared to higher grades. Hypothesis testing performed on volume heterogeneity index showed P values of 0.0002 (0.0001) and 0.0003 (0.0003) between grades II vs. III and III vs. IV, respectively, for MD (MK). CONCLUSION: In summary, the studies demonstrated great potential towards automating grading gliomas by employing tumour heterogeneity measures on DTI and DKI parameters.

Response of central nervous system aspergillosis to voriconazole.

Fungal infections of the central nervous system (CNS) usually present as subacute meningitis. Other manifestations include mass effect and focal neurological deficits. Cerebrospinal fluid (CSF) examination and biopsy of the lesion are helpful in disclosing the organism involved. Aspergillosis presents as brain abscess or granuloma with predominant neutrophils in CSF. Voriconazole is a broad spectrum triazole antifungal agent. It can be given orally and has lesser adverse effects We report a 69-years-old diabetic male, with aspergilloma of para-nasal sinus invading the CNS, who responded well to voriconazole treatment. He discontinued the medication by himself as it was costly. Within a month of stopping the medication, he developed features of subacute meningitis. However he showed clinical improvement after the medication was restarted. The case is reported for the clinical evidence of antifungal activity of voriconazole against aspergillosis.