Diffusion and perfusion imaging biomarkers of H3 K27M mutation status in diffuse midline gliomas.

PURPOSE: H3K27M-mutant diffuse midline gliomas (M-DMGs) exhibit a clinically aggressive course. We studied diffusion-weighted imaging (DWI) and perfusion (PWI) MRI features of DMG with the hypothesis that DWI-PWI metrics can serve as biomarkers for the prediction of the H3K27M mutation status in DMGs. METHODS: A retrospective review of the institutional database (imaging and histopathology) of patients with DMG (July 2016 to July 2020) was performed. Tumoral apparent diffusion coefficient (ADC) and peritumoral ADC (PT ADC) values and their normalized values (nADC and nPT ADC) were computed. Perfusion data were analyzed with manual arterial input function (AIF) and leakage correction (LC) Boxerman-Weiskoff models. Normalized maximum relative CBV (rCBV) was evaluated. Intergroup analysis of the imaging variables was done between M-DMGs and wild-type (WT-DMGs) groups. RESULTS: Ninety-four cases (M-DMGs-n = 48 (51%) and WT-DMGs-n = 46(49%)) were included. Significantly lower PT ADC (mutant-1.1 ± 0.33, WT-1.23 ± 0.34; P = 0.033) and nPT ADC (mutant-1.64 ± 0.48, WT-1.83 ± 0.54; P = 0.040) were noted in the M-DMGs. The rCBV (mutant-25.17 ± 27.76, WT-13.73 ± 14.83; P = 0.018) and nrCBV (mutant-3.44 ± 2.16, WT-2.39 ± 1.25; P = 0.049) were significantly higher in the M-DMGs group. Among thalamic DMGs, the min ADC, PT ADC, and nADC and nPT ADC were lower in M-DMGs while nrCBV (corrected and uncorrected) was significantly higher. Receiver operator characteristic curve analysis demonstrated that PT ADC (cut-off-1.245), nPT ADC (cut-off-1.853), and nrCBV (cut-off-1.83) were significant independent predictors of H3K27M mutational status in DMGs. CONCLUSION: DWI and PWI features hold value in preoperative prediction of H3K27M-mutation status in DMGs.

Imaging features of rosette-forming glioneuronal tumours (RGNTs): A Series of seven cases.

OBJECTIVE: Rosette-forming glioneuronal tumours (RGNTs) are a recently described, rare, distinct nosological entity of the glioneuronal family. We describe imaging findings (CT and MRI) in seven patients with RGNTs. MATERIALS AND METHODS: This retrospective study includes seven RGNT patients (4 male, 3 female; age range: 7-42 years; mean age: 25 years) diagnosed and treated at our institute. MR studies were performed on 3 T and 1.5-T clinical MR systems. All patients were reviewed by two experienced neuroradiologists and imaging findings were tabulated. RESULTS: Five tumours were located in the posterior fossa, and two were in the pineal region. One of the tumours demonstrated multiple satellite lesions, which involved the midbrain, pons, medulla as well as the cervical cord. Tumours located in the pineal region compressed the 3rd ventricle/aqueduct and extended below the tentorium cerebelli. All the tumours demonstrated enhancement, and susceptibility was evident in six of the seven patients. CSF dissemination was present in two patients. CONCLUSION: RGNTs are usually solid-cystic tumours and frequently demonstrate peripheral/heterogeneous enhancement upon post-contrast study. Haemorrhage is a common feature which may not be evident on CT. Cerebrospinal fluid (CSF) dissemination is a feature and appropriate imaging should be performed whenever an RGNT is suspected. KEY POINTS: CT and MRI findings of seven RGNT cases were retrospectively reviewed. RGNTs are predominantly posterior fossa tumours. RGNTs are typically T1 hypointense and T2 hyperintense. Haemorrhage and peripheral/heterogeneous enhancement are common features of RGNTs. CSF dissemination is a feature of RGNTs and requires appropriate imaging.

Novel imaging findings in two cases of biotinidase deficiency-a treatable metabolic disorder.

Biotinidase deficiency is one of the few treatable inborn errors of metabolism. We describe unique MRI features in two patients with biotinidase deficiency. Brain MRI in case one demonstrated symmetrical diffusion restriction in bilateral hippocampi, parahippocampal gyri, central tegmental tracts, and cerebellar white matter besides other structures that have been reported previously. The second patient was noted to have bilateral symmetrical T2 hyperintensities involving the anterior, lateral and posterior columns of the entire spinal cord on MRI. Knowledge of the varied MRI features of biotinidase deficiency will aid the prompt diagnosis and treatment of a potentially disabling illness, especially in countries where newborn screening is not routinely performed.

Cribriform Appearance of White Matter in Canavan Disease Associated with Novel Mutations of ASPA Gene.

Cribriform appearance of the brain in Canavan disease is a rare finding. The two presented cases broaden the magnetic resonance imaging (MRI) phenotype wherein numerous oval, cystic structures, a few resembling dilated Virchow-Robin (VR) spaces, were noted in the centrum semiovale, periventricular, and lobar white matter producing a cribriform pattern. Besides, discrete round to oval cysts were present at the gray-white matter junctions in the second case, which were larger and appeared morphologically distinct from the VR spaces. These cysts did not elongate in any plane on imaging and were more representative of giant intramyelinic vacuoles. Genetic analysis revealed novel mutations in the aspartoacylase or ASPA gene that possibly accounts for the severe form of Canavan disease, which probably explains the imaging findings. The multicystic appearance of the white matter in Canavan disease is unusual and possibly represents two different histopathological substrates.

Neuroimaging Findings in Rabies Encephalitis.

BACKGROUND AND PURPOSE: Rabies encephalitis is a near-fatal zoonotic disease that is usually diagnosed on clinical grounds in conjunction with characteristic history. Owing to its rapidly progressive nature, imaging is seldom performed, and hence a description of imaging findings in rabies encephalitis is anecdotal and limited. METHODS: We describe MRI findings in eight confirmed rabies cases that presented to our institute over the last 21 years. RESULTS: Most of the patients' imaging patterns are in concordance with the described literature. However, we hereby demonstrate the involvement of novel structures like dentate nuclei, cranial nerves, and meninges besides the hot cross bun sign in the pons and the presence of diffusion restriction in many gray and white matter structures of the brain. CONCLUSION: Knowledge of the broad imaging spectrum of rabies may expedite the diagnosis, especially the paralytic form, which is prone to clinical misdiagnosis as Guillain-Barre syndrome or acute disseminated encephalomyelitis.

Prediction of H3K27M mutation status of diffuse midline gliomas using MRI features.

BACKGROUND AND PURPOSE: Presurgical prediction of H3K27M mutation in diffuse midline gliomas (DMGs) on MRI is desirable. The purpose of this study is to elaborate conventional MRI (cMRI) features of H3K27M-mutant DMGs and identify features that could discriminate them from wild-type (WT) DMGs. METHODS: CMRI features of 123 patients with DMG were evaluated conforming to the institutional research protocols. Multimodality MRI was performed on 1.5 or 3.0 Tesla MR Scanners with imaging protocol, including T1-weighted (w), T2w, fluid-attenuated inversion recovery, diffusion-weighted, susceptibility-weighted, and postcontrast T1w sequences. Pertinent cMRI features were annotated along the lines of Visually AcceSAble Rembrandt Images features, and Intra Tumoral Susceptibility Signal score (ITSS) was evaluated. R software was used for statistical analysis. RESULTS: Sixty-one DMGs were H3K27M-mutant (mutant DMGs). The patients in the H3K27M-mutant DMG group were younger compared to the WT-DMG group (mean age 24.13 ± 13.13 years vs. 35.79±18.74 years) (p = 0.016). The two groups differed on five cMRI features--(1) enhancement quality (p = 0.032), (2) thickness of enhancing margin (p = 0.05), (3) proportion of edema (p = 0.002), (4) definition of noncontrast-enhancing tumor (NCET) margin (p = 0.001), and (5) cortical invasion (p = 0.037). The mutant DMGs showed greater enhancement and greater thickness of enhancing margin, while the WT DMGs exhibited significantly larger edema proportion with poorly defined NCET margins and cortical invasion. ITSS was not significantly different among the groups. CONCLUSION: CMRI features like enhancement quality, the thickness of the enhancing margin, proportion of edema, definition of NCET margin, and cortical invasion can discriminate between the H3K27M-mutant and WT DMGs.

First report of COVID-19-associated rhino-orbito-cerebral mucormycosis in pediatric patients with type 1 diabetes mellitus.

Coronavirus disease 2019 (COVID-19) is a major public health problem worldwide. These patients are at increased risk of developing secondary infections due to a combination of virus- and drug-induced immunosuppression. Recently, several countries have reported an emergence of COVID-19 associated mucormycosis (CAM), particularly among patients with uncontrolled diabetes, with India reporting an alarming increase in rhino-orbito-cerebral mucormycosis (ROCM) in post-COVID cases. Hyperglycemia and diabetic ketoacidosis (DKA) are the major underlying risk factors. So far, case reports and review articles have reported CAM only in adult patients. Here, we describe the first cases of COVID-19-associated ROCM in two pediatric patients with Type 1 diabetes mellitus (DM). Both the cases had asymptomatic infection with SARS-CoV-2 and developed ROCM during the course of treatment of DKA. None of them had exposure to systemic steroids. Imaging findings in both cases revealed involvement of orbit, paranasal sinuses, and brain with cavernous sinus thrombosis. The patients underwent craniotomy with evacuation of abscess. Microbiological and histopathological findings were consistent with the diagnosis of mycormycosis, with fungal culture growing Rhizopus arrhizus. Post-operatively, the patients received liposomal amphotericin B (LAMB) and systemic antibiotics. Retrobulbar injection of LAMB was given in an attempt to halt orbital disease progression. However, it wasn't successful and both of them had to undergo orbital exenteration eventually. ROCM is a rapidly progressive disease and prompt diagnosis with aggressive surgery and timely initiation of antifungal therapy can be life-saving. Physicians should have a high index of suspicion, so as to avoid a delayed diagnosis, particularly in post-COVID patients with uncontrolled diabetes.

Clinical, neuroimaging and therapeutic response in AQP4-positive NMO patients from India.

BACKGROUND: Neuromyelitis Optica (NMO) is an autoimmune astrocytopathic disorder due to AQP4 antibodies. OBJECTIVES: To analyse clinical, neuroimaging features in NMO patients and assess the efficacy of various therapeutics. METHODS: AQP4+ve NMO patients were diagnosed based on consensus diagnostic criteria. RESULTS: 101 AQP4+ve NMO patients were seen with female (90) predominance. Adult population (71.3%) formed the larger group followed by pediatric (19.8%) and late-onset (8.9%). Myelopathy (36.2%) was most commonly seen followed by optic neuritis (19.1%), brainstem (17.1%), opticomyelopathy (16.1%), area postrema involvement (10.5%) and encephalopathy (1%). Encephalopathy and brainstem/cerebellar involvement were most common in pediatric population while opticomyelopathy was more common in late-onset patients. Hyperintensities of lower medulla was seen in 67.3% subjects and 49.5% had involvement of obex. Differential T2 hyperintensity of the long segment myelitis was found in 30.7%. Plasmapheresis was given in 71 subjects followed by maintenance therapy. Most of them showed significant improvement with EDSS score of 1 in 30.7%. CONCLUSIONS: Clinical manifestations in AQP4+ve NMO patients may vary depending on the age at onset of illness. MRI features affecting cervicomedullary junction, obex, differential T2 hyperintensities of the spinal cord may form a useful diagnostic clue. Plasmapheresis is helpful in achieving remission along with immunomodulation.

Diffusion restriction in ethylmalonic encephalopathy - An imaging evidence of the pathophysiology of the disease.

Ethylmalonic encephalopathy is an inborn error of metabolism characterized by encephalopathy, petechiae chronic diarrhea and acrocyanosis. Imaging findings include patchy signal changes in the basal ganglia, periaqueductal region, subcortical white matter and cerebellum. We describe the novel finding of diffusion restriction in brain lesions, in a proven case of ethylmalonic encephalopathy.