Novel TBK1 variant associated with Frontotemporal Dementia overlap syndrome.

BACKGROUND: Recently, TANK binding kinase 1 (TBK1) mutation has been reported as a causative gene for overlap frontotemporal dementia (FTD)-amyotrophic lateral sclerosis (ALS) syndrome. However, there are no reports from families of South Asian ethnicity. OBJECTIVE: To report a case study of a family with the proband having overlap FTD-ALS syndrome caused by a novel TBK1 variant. MATERIALS AND METHODS: Clinical, brain imaging, genetic analysis and laboratory data of the patient with FTD-ALS were performed. In addition, family-based segregation analysis of identified novel variants was also done. RESULTS: This study pertains to genetic analysis in 11 members in a family with only one member affected with overlap FTD-ALS syndrome. The whole-exome sequencing analysis in the symptomatic member showed a novel loss-of-function (LoF) variant c.1810G>T(p.E604X) in the TBK1 gene. Neuroimaging showed a pattern of asymmetric frontotemporal atrophy and hypometabolism. Segregation analysis of the variation demonstrated its presence in several family members, although none of the other members was symptomatic. Further, we observed another missense variation in the NEFH gene (p.Pro683Leu) which was seen in the symptomatic and two asymptomatic family members, the pathogenicity of which is unclear. CONCLUSION: This is the first study of a rare novel TBK1 variant associated with FTD-ALS from India. Asymptomatic family members with the variant have important clinical implications and necessitate the genetic evaluation and long-term follow-up of family members of patients detected with TBK1 mutations. Therefore, although infrequent, genetic screening for the TBK1 gene should be considered when encountering overlap FTD syndromes.

Abusive head trauma in India: imaging raises the curtain.

The purpose of the study was to identify children at our institute who possibly suffered abusive head trauma (AHT). A retrospective study of CT imaging of children between one month to three years of age between January 2013 and May 2021 was carried out at a dedicated neurocentre in Southern India. We identified 48 cases of possible AHT. The demographics, clinical features at presentation, imaging and fundus findings were analyzed. Imaging revealed subdural hemorrhage (SDH) in 42 and sub dural effusion (SDE) in 5 cases, one case had only hypoxia. The location of SDH was studied as was hypoxia underlying SDH, global hypoxia and ischemia. Cases of subarachnoid hemorrhage (SAH), parenchymal hematoma & intraventricular hemorrhage (IVH) were also noted. Skeletal survey, chest X-ray and CT spine were reviewed. AHT needs to be paid attention to in the Indian scenario. An extensive work up is required to substantiate the claim and to work on prevention & management of these cases subsequently.

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.

Can High b Value Diffusion Be a Surrogate Marker for PET-A MR/PET Study in Neurooncology Set Up.

Purpose: Hybrid whole-body magnetic resonance/positron emission tomography (MR/PET) systems are new diagnostic tools enabling the simultaneous acquisition of morphologic and multiparametric functional data, which allow for a diversified characterization of oncological diseases. This study aimed to compare the diagnostic ability of MRI with the diffusion-weighted image (DWI), and simultaneous integrated positron emission tomography MR/PET to detect malignant lesions and elucidate the utility and limitations of these imaging modalities in preoperative and postoperative follow up in cancer patients. Material and Methods: A total of 45 patients undergoing simultaneous MR/PET for CNS ICSOL in our institution between January 2016 and July 2020 were considered in this study. Post-processing was done in Siemens syngo software to generate a b2000 image. This image was then inverted to grayscale and compared with the NAC image of PET. Results: The lesion-based sensitivity, specificity, positive predictive value, and negative predictive value for DWI were 92.3, 83.3, 97.3, and 62.5%, respectively (at 95% CI and p was 0.000). The lesion-based sensitivity, specificity, positive predictive value, and negative predictive value for PET were 97.4, 71.4, 94.9, and 83.3%, respectively (at 95% CI and p was 0.000). The lesion-based sensitivity and specificity of DWI were comparable with those of PET. Conclusions: Although DWI and FDG-PET reflect different tissue properties, there is an association between the measures of both methods in CNS tumors probably because of the coupling of cellularity with tumor metabolism as seen on FDG and other PET tracers. Our study shows that DWI acts as a surrogate biomarker for FDG PET and other tracers in tumors. The method of DWI image generation is simple, radiation-free, and cost-effective in a clinical setup. The simultaneous DWI-PET study provides evidence and confirms the role of DWI in surveillance imaging of tumors.

Combined amino acid PET-MRI for identifying recurrence in post-treatment gliomas: together we grow.

PURPOSE: The aim of this study is to compare the diagnostic accuracy of amino acid PET, MR perfusion and diffusion as stand-alone modalities and in combination in identifying recurrence in post-treatment gliomas and to qualitatively assess spatial concordance between the three modalities using simultaneous PET-MR acquisition. METHODS: A retrospective review of 48 cases of post-treatment gliomas who underwent simultaneous PET-MRI using C11 methionine as radiotracer was performed. MR perfusion and diffusion sequences were acquired during the PET study. The following parameters were obtained: TBRmax, TBRmean, SUVmax, and SUVmean from the PET images; rCBV from perfusion; and ADCmean and ADCratio from the diffusion images. The final diagnosis was based on clinical/imaging follow-up and histopathology when available. ROC curve analysis in combination with logistic regression analysis was used to compare the diagnostic performance. Spatial concordance between modalities was graded as 0, 1, and 2 representing discordance, < 50% and > 50% concordance respectively. RESULTS: There were 35 cases of recurrence and 13 cases of post-treatment changes without recurrence. The highest area under curve (AUC) was obtained for TBRmax followed by rCBV and ADCratio. The AUC increased significantly with a combination of rCBV and TBRmax. Amino acid PET showed the highest diagnostic accuracy and maximum agreement with the final diagnosis. There was discordance between ADC and PET in 22.9%, between rCBV and PET in 16.7% and between PET and contrast enhancement in 14.6% cases. CONCLUSION: Amino acid PET had the highest diagnostic accuracy in identifying recurrence in post-treatment gliomas. Combination of PET with MRI further increased the AUC thus improving the diagnostic performance.

Developing a Radiomics Signature for Supratentorial Extra-Ventricular Ependymoma Using Multimodal MR Imaging.

Rationale and Objectives: To build a machine learning-based diagnostic model that can accurately distinguish adult supratentorial extraventricular ependymoma (STEE) from similarly appearing high-grade gliomas (HGG) using quantitative radiomic signatures from a multi-parametric MRI framework. Materials and Methods: We computed radiomic features on the preprocessed and segmented tumor masks from a pre-operative multimodal MRI dataset [contrast-enhanced T1 (T1ce), T2, fluid-attenuated inversion recovery (FLAIR), apparent diffusion coefficient (ADC)] from STEE (n = 15), HGG-Grade IV (HGG-G4) (n = 24), and HGG-Grade III (HGG-G3) (n = 36) patients, followed by an optimum two-stage feature selection and multiclass classification. Performance of multiple classifiers were evaluated on both unimodal and multimodal feature sets and most discriminative radiomic features involved in classification of STEE from HGG subtypes were obtained. Results: Multimodal features demonstrated higher classification performance over unimodal feature set in discriminating STEE and HGG subtypes with an accuracy of 68% on test data and above 80% on cross validation, along with an overall above 90% specificity. Among unimodal feature sets, those extracted from FLAIR demonstrated high classification performance in delineating all three tumor groups. Texture-based radiomic features particularly from FLAIR were most important in discriminating STEE from HGG-G4, whereas first-order features from T2 and ADC consistently ranked higher in differentiating multiple tumor groups. Conclusions: This study illustrates the utility of radiomics-based multimodal MRI framework in accurately discriminating similarly appearing adult STEE from HGG subtypes. Radiomic features from multiple MRI modalities could capture intricate and complementary information for a robust and highly accurate multiclass tumor classification.

Clinicomycological overview of brain abscess in a tertiary care center: A 38 year retrospection: Fungal brain abscess.

INTRODUCTION: Brain abscesses (BA) form approximately 8% of intracranial masses in developing and 1-2% in western countries. Fungal BA (FBA) are aggressive and represent a catastrophic manifestation compared to protozoan and bacterial BA. Diagnosis of FBA is rare and usually done postmortem. OBJECTIVES: The present retrospective study analyses the clinico-mycological aspects of FBA presented to our neurosurgical services over a period of 38 years, from January 1979 to April 2017. MATERIALS AND METHODS: Patients diagnosed as definitive cases of FBA were included in the study. Clinico- demographic and microbiological data were collected from medical records. BA pus was examined for fungal etiology using standard microbiological procedures. RESULTS: During the period of 38 years out of total 2,916 brain abscesses, 29 cases of FBA were diagnosed with an overall incidence rate of 0.99% per year. Cladophialophora bantiana (44%) was the most predominant isolate followed by Aspergillus spp and others. Male preponderance was seen with a male:female ratio of 4.8:1. There was no predilection for any age group. Headache, limb weakness and fever were the most common presentations. Amphotericin B was given in 44.8% of cases. Craniotomy with excision (48.2%) was the predominant surgical management. Outcome was fatal in 62% of the cases. CONCLUSION: Neurotropic C. bantiana is the predominant isolate causing fungal brain abscess. The incidence and trends of fungi causing brain abscess do not show significant change. Young immunocompetent outdoor working males were predominantly susceptible to fungal infection. Advance in the diagnostic modalities show promising in diagnosis of FBA. High index of suspicion with early diagnosis, prompt antifungal therapy and aggressive surgical management is required as FBA are associated with high mortality rate.

Amide proton transfer imaging for differentiation of tuberculomas from high-grade gliomas: Preliminary experience.

PURPOSE: Tuberculomas can occasionally masquerade as high-grade gliomas (HGG). Evidence from magnetisation transfer (MT) imaging suggests that there is lower protein content in the tuberculoma microenvironment. Building on the principles of chemical exchange saturation transfer and MT, amide proton transfer (APT) imaging generates tissue contrast as a function of the mobile amide protons in tissue's native peptides and intracellular proteins. This study aimed to further the understanding of tuberculomas using APT and to compare it with HGG. METHOD: Twenty-two patients (n = 8 tuberculoma; n = 14 HGG) were included in the study. APT was a 3D turbo spin-echo Dixon sequence with inbuilt B0 correction. A two-second, 2 µT saturation pulse alternating over transmit channels was applied at ±3.5 ppm around water resonance. The APT-weighted image (APTw) was computed as the MT ratio asymmetry (MTRasym) at 3.5 ppm. Mean MTRasym values in regions of interest (areas = 9 mm2; positioned in component with homogeneous enhancement/least apparent diffusion coefficient) were used for the analysis. RESULTS: MTRasym values of tuberculomas (n = 14; 8 cases) ranged from 1.34% to 3.11% (M = 2.32 ± 0.50). HGG (n = 17;14 cases) showed MTRasym ranging from 2.40% to 5.70% (M = 4.32 ± 0.84). The inter-group difference in MTRasym was statistically significant (p < 0.001). APTw images in tuberculomas were notable for high MTRasym values in the perilesional oedematous-appearing parenchyma (compared to contralateral white matter; p < 0.001). CONCLUSION: Tuberculomas demonstrate lower MTRasym ratios compared to HGG, reflective of a relative paucity of mobile amide protons in the ambient microenvironment. Elevated MTRasym values in perilesional parenchyma in tuberculomas are a unique observation that may be a clue to the inflammatory milieu.

Persistent Primitive Olfactory Artery: Three Cases.

ABSTRACT: The persistent primitive olfactory artery is a very rare arterial variant with a little over a score of cases reported in literature so far. We present 3 cases illustrating this entity, which were incidentally diagnosed while imaging for other indications.

Dissecting aneurysms of the posterior cerebral artery - A retrospective review of imaging, angiographic characteristics, endovascular management and outcome.

PURPOSE: To review management, clinical and imaging outcomes of dissecting posterior cerebral artery (PCA) aneurysms with emphasis on endovascular management in the form of parent vessel occlusion (PVO) at a tertiary care center. METHODS: Thirty-six dissecting PCA aneurysms (19 ruptured) encountered at our center between January 2013 and November 2019 were reviewed for aneurysm location/size/presence of fetal PCA/management. Postprocedural imaging of patients who underwent endovascular intervention was reviewed for PCA territory infarcts and clinical records assessed for presence of neuro-deficits and outcome. None of the patients underwent a balloon test occlusion (BTO) prior to PVO. RESULTS: The location of the aneurysms was as follows-P1 = 8/P1-P2 = 11/P2 = 5/P2-P3 = 10/P3 = 2. The mean size was 11.7x6.8 mm. Endovascular intervention was carried out in 20 patients in the form of PVO with coiling in 16 patients, coiling alone in 3 patients, and reconstruction of the left PCA with flow diverter deployment in one patient. Postprocedural PCA territory infarct was seen in 5 cases of PVO out of which 4 had a good functional recovery. Overall, 15/16 patients (93.7%) who underwent PVO had mRS ≤ 2 on follow-up. The single case with flow diverter also developed an infarct and had adverse outcome on follow up. CONCLUSION: Among the various management strategies for dissecting PCA aneurysms, PVO is feasible and relatively safe even in absence of BTO in scenarios like critically ill patients with ruptured aneurysms, difficult access and financial constraints. Thromboembolic complications and antiplatelet therapy is a concern in reconstructive strategies.

Ruptured vertebrobasilar junction aneurysm unmasking subclavian steal syndrome.

BACKGROUND: Subclavian steal occurs due to stenosis or occlusion of the subclavian artery or innominate artery proximal to the origin of the vertebral artery. Often asymptomatic, the condition may be unmasked due to symptoms of vertebrobasilar insufficiency triggered by strenuous physical exercise involving the affected upper limb. The association of vertebrobasilar junction (VBJ) aneurysms with subclavian steal syndrome has been rarely reported. Hereby, we present a case of VBJ aneurysm associated with subclavian steal treated successfully with endovascular coiling. CASE DESCRIPTION: A 65-year-old female presented in the emergency department with acute severe headache and vomiting with no focal neurological deficits. Non-contrast computed tomography of the brain showed modified Fischer Grade 3 subarachnoid hemorrhage. Subsequent digital subtraction angiogram (DSA) showed VBJ aneurysm directed inferiorly with the left subclavian artery occlusion. There was retrograde filling of the left vertebral artery on right vertebral injection, confirming the diagnosis of subclavian steal. Balloon assisted coiling of the VBJ aneurysm was performed while gaining access through the stenotic left vertebral artery ostium which provided a more favorable hemodynamic stability to the coil mass. CONCLUSION: Subclavian steal exerting undue hemodynamic stress on vertebrobasilar circulation can be an etiological factor for the development of the flow-related aneurysms. Access to the VBJ aneurysms may be feasible through the stenosed vertebral artery if angioplasty is performed before the coiling of the aneurysm.

Conventional and Advanced Magnetic Resonance Imaging Features of Supratentorial Extraventricular Ependymomas.

OBJECTIVE: To describe the magnetic resonance imaging characteristics of supratentorial ependymomas. METHODS: The magnetic resonance imaging and computed tomography imaging characteristics of 49 cases of supratentorial ependymomas were analyzed retrospectively. The location, size, degree of perilesional edema, gross appearance, computed tomography attenuation characteristics, T1 and T2 signal intensity characteristics, degree of diffusion restriction, presence of calcification, and hemorrhage were documented for each lesion. The intratumoral susceptibility scores (ITSS), apparent diffusion coefficient (ADC) values, relative cerebral blood volume, and choline/N-acetyl aspartate ratios were documented where available. RESULTS: The frontal lobe was the most common location with a mean size of 6.37 × 4.8 cm. Severe perilesional edema was evident in 30%. Heterogenous, solid-cystic appearance was present in 96% lesions, with 95% of extraventricular lesions extending from pial surface to the ventricular margin. Calcification was seen in 55% of cases. The ITSS was 3 in 85.7% of lesions. The mean ADC value calculated was 600 × 10 mm/s. The mean relative cerebral blood volume on dynamic susceptibility contrast perfusion was 4.83. The mean choline/N-acetyl aspartate ratio was 5.87. Leptomeningeal dissemination was demonstrable in 5 lesions. Four lesions were abutting the dura with frank dural invasion in one. One patient presented with disseminated disease without evidence of a primary lesion. CONCLUSIONS: A large lesion with relatively well-defined margins, heterogeneous solid cystic appearance, extending from the pial surface to the ventricular margin, presence of calcification, and ADC values approaching those of white matter should raise a suspicion of supratentorial ependymoma. High ITSS, MR perfusion parameters, and magnetic resonance spectroscopy characteristics are similar to those of other high-grade gliomas.

Brain and Spinal Cord Lesions in Leprosy: A Magnetic Resonance Imaging-Based Study.

Neurotropism and infiltration by Mycobacterium leprae of peripheral nerves causing neuropathy are well established, but reports of central nervous system (CNS) damage are exceptional. We report CNS magnetic resonance imaging (MRI) abnormalities of the brain and spinal cord as well as lesions in nerve roots and plexus in leprosy patients. Eight patients aged between 17 and 41 years underwent detailed clinical, histopathological, and MRI evaluation. All had prominent sensory-motor deficits with hypopigmented and hypo/anesthetic skin patches and thickened peripheral nerves. All demonstrated M. Leprae DNA in affected peripheral nerve tissue. All received multidrug therapy (MDT). Two patients had brainstem lesions with enhancing facial nuclei and nerves, and one patient had a lesion in the nucleus ambiguus. Two patients had enhancing spinal cord lesions. Follow-up MRI performed in four cases showed resolution of brainstem and cord lesions after starting on MDT. Thickened brachial and lumbosacral plexus nerves were observed in six and two patients, respectively, which partially resolved on follow-up MRI in the two cases who had reimaging. The site and side of the MRI lesions corresponded with the location and side of neurological deficits. This precise clinico-radiological correlation of proximal lesions could be explained by an immune reaction in the gray matter corresponding to the involved peripheral nerves, retrograde axonal and gray matter changes, or infection of the CNS and plexus by lepra bacilli. Further study of the CNS in patients with leprous neuropathy is needed to establish the exact nature of these CNS MRI findings.

Spectrum of biliary abnormalities in portal cavernoma cholangiopathy (PCC) secondary to idiopathic extrahepatic portal vein obstruction (EHPVO)-a prospective magnetic resonance cholangiopancreaticography (MRCP) based study.

OBJECTIVE: To characterize biliary abnormalities seen in portal cavernoma cholangiopathy (PCC) on MR cholangiopancreaticography (MRCP) and elucidate certain salient features of the disease by collaborating our findings with those of previous studies. METHODS: We prospectively enrolled 52 patients with portal cavernoma secondary to idiopathic extrahepatic portal vein obstruction, who underwent a standard MRCP protocol. Images were analyzed for abnormalities involving the entire biliary tree. Terms used were those proposed by the Indian National Association for Study of the Liver. Angulation of the common bile duct (CBD) was measured in all patients with cholangiopathy. RESULTS: Cholangiopathy was seen in 80.7% of patients on MRCP. Extrahepatic ducts were involved in 95% of patients either alone (26%) or in combination with the intrahepatic ducts (69%). Isolated involvement of the intrahepatic ducts was seen in 4.8% of patients. Abnormalities of the extrahepatic ducts included angulation (90%), scalloping (76.2%), extrinsic impression/indentation (45.2%), stricture (14.3%) and smooth dilatation (4.8%). The mean CBD angle was 113.2 ± 19.8°. Abnormalities of the intrahepatic ducts included smooth dilatation (40%), irregularity (28%) and narrowing (9%). Cholelithiasis, choledocholithiasis and hepatolithiasis were seen in 28.6% (12) patients, 14.3% (6) patients and 11.9% (5) patients, respectively. There was a significant association between choledocholithiasis and CBD stricture, with no significant association between choledocholithiasis and cholelithiasis. A significant association was also seen between hepatolithiasis and choledocholithiasis. CONCLUSION: The spectrum of biliary abnormalities in PCC has been explored and some salient features of the disease have been elucidated, which allow a confident diagnosis of this entity. Advances in knowledge: PCC preferentially involves the extrahepatic biliary tree. Changes in the intrahepatic ducts generally occur as sequelae of involvement of the extrahepatic ducts, although isolated involvement of the intrahepatic ducts does occur. Increased angulation of the CBD and scalloping are most commonly seen. Angulation may predispose to choledocholithiasis and thus development of symptomatic cholangiopathy. Choledocholithiasis and hepatolithiasis occur as sequelae of PCC.

Primary cerebellar agenesis presenting as isolated cognitive impairment.

Primary cerebellar agenesis is a rare entity. To the best of our knowledge, eleven living cases have been reported till date. Most of these were associated with some degree of motor impairment. We present a case of cerebellar agenesis in a child who presented with cognitive abnormalities leading to poor performance at school. No motor impairment was seen. Among the eleven cases reported earlier, only one case showed lack of motor impairment.