Hypomyelination caused by a novel homozygous pathogenic variant in FOLR1: complete clinical and radiological recovery with oral folinic acid therapy and review of the literature.

BACKGROUND: Neurodegeneration due to cerebral folate transport deficiency is a rare autosomal recessive disorder caused by biallelic pathogenic variants in FOLR1. Onset typically occurs in late infancy and is characterized by psychomotor regression, epilepsy, and a hypomyelinating leukodystrophy on magnetic resonance imaging. If left untreated, progressive neurodegeneration occurs. However, early treatment with folinic acid has been shown to stabilize or reverse neurological features. Approximately thirty patients have been described worldwide. Here, we report the first two cases with genetically proven cerebral folate transport deficiency from South-Eastern Europe, describe the effect of oral folinic acid therapy on clinical and neuroradiological features and review the literature. RESULTS: Two siblings presented in childhood with clinical and radiological findings consistent with a hypomyelinating leukodystrophy. Exome sequencing revealed a novel homozygous pathogenic variant in FOLR1 (c.465_466delinsTG; p.W156G), confirming the diagnosis of neurodegeneration due to cerebral folate transport deficiency. Folinic acid treatment was promptly initiated in both patients. The younger sibling was treated early in disease course at 2 years of age, and demonstrated complete recovery in clinical and MRI features. The older sibling, who was 8 years of age at the time of diagnosis and treatment, demonstrated partial but substantial improvements. CONCLUSION: We present the first account in the literature that early treatment initiation with oral folinic acid alone can result in complete neurological recovery of both clinical and radiological abnormalities in neurodegeneration due to cerebral folate deficiency. Moreover, through the report of these patients along with review of the literature, we provide information about the natural history of the disease with comparison of treatment effects at different stages of disease progression. This report also reinforces the importance of universal access to genetic testing to ensure prompt diagnoses for treatable disorders.

Computational quantitative MR image features - a potential useful tool in differentiating glioblastoma from solitary brain metastasis.

PURPOSE: Glioblastomas (GBM) and metastases are the most frequent malignant brain tumors in the adult population. Their presentation on conventional MRI is quite similar, but treatment strategy and prognosis are substantially different. Even with advanced MR techniques, in some cases diagnostic uncertainty remains. The main objective of this study was to determine whether fractal, texture, or both MR image analyses could aid in differentiating glioblastoma from solitary brain metastasis. METHOD: In a retrospective study of 55 patients (30 glioblastomas and 25 solitary metastases) who underwent T2W/SWI/CET1 MRI, quantitative parameters of fractal and texture analysis were estimated, using box-counting and gray level co-occurrence matrix (GLCM) methods. RESULTS: All five GLCM parameters obtained from T2W images showed significant difference between glioblastomas and solitary metastases, as well as on CET1 images except correlation (SCOR), contrary to SWI images which showed different values of two parameters (angular second moment-SASM and contrast-SCON). Only three fractal features (binary box dimension-Dbin, normalized box dimension-Dnorm and lacunarity-λ) measured on T2W and Dnorm measured on CET1 images significantly differed GBMs from solitary metastases. The highest sensitivity and specificity were obtained from inverse difference moment (SIDM) on T2W and SIDM on CET1 images, respectively. Combination of several GLCM parameters yielded better results. The processing of T2W images provided the most significantly different parameters between the groups, followed by CET1 and SWI images. CONCLUSIONS: Computational-aided quantitative image analysis may potentially improve diagnostic accuracy. According to our results texture features are more significant than fractal-based features in differentiation glioblastoma from solitary metastasis.

Differentiation between progression and pseudoprogresion by arterial spin labeling MRI in patients with glioblastoma multiforme.

PURPOSE: To compare arterial spin labeling (ASL) perfusion technique with the clinically established dynamic susceptibility contrast-enhanced (DSC) perfusion weighted-imaging (PWI), and to determine its value in routine MRI evaluation of disease progression in patients with glioblastoma multiforme (GBM). METHODS: A prospective intraindividual study was performed in 31 patients with histologically proven GBM who had clinical and/or radiological deterioration after treatment, including surgery, radiotherapy and therapy with temozolomide. Conventional brain protocol with ASL and DSC techniques was performed on 3T MRI unit. Cerebral blood flow (CBF) and cerebral blood volume (CBV) maps were analyzed by means of regions of interest (ROI). Each ROI average value was normalized to the contralateral normal brain parenchyma ROI value. Neuroradiologists analyzed CBF and CBV maps separately, and classified patients into progression or pseudoprogression group. Radiological diagnosis was confirmed by clinical-radiological follow-up for at least three months after patient deterioration. RESULTS: High linear correlation existed between DSC-PWI and ASL in the tumor ROI (r=0.733; p<0.001). 92% of ASL CBF maps were informative. ASL detected all lesions as well as DSC MRI. Both techniques provided perfusion values closely correlated. CONCLUSION: ASL allows distinction between GBM progression and pseudoprogression, and it can be used as reliable alternative to DSC-PWI.

Proton magnetic resonance spectroscopy and apparent diffusion coefficient in evaluation of solid brain lesions.

BACKGROUND/AIM: Advanced magnetic resonance techniques can provide insight in physiological changes within pathological canges and contribute to better distinquishing between different tumor types and their discrimination from non-neoplastic lesions. The aim of this study was to evaluate the role of proton magnetic resonance spectroscopy (1H-MRS) and apparent diffusion coefficients (ADC) in distinguishing intracranial glial tumors from tumor like nonneoplastic lesions, as well as for differentiating high- from low-grade gliomas. METHODS: This retrospective study included 47 patients with solid brain lesions (25 nonneoplastic, 14 low-grade and 8 anaplastic glial tumors). In all patients 1H-MRS (at a TE of 135 ms and 30 ms) and diffusion-weighted imaging (DWI) were performed. The choline to creatine (Cho/Cr), choline to N-acetyl aspartate (Cho/NAA), N-acetyl aspartate to creatine (NAA/Cr) and myoinositol to creatine (mIn/Cr) ratios and the apparent diffusion coefficient (ADC) were determined. RESULTS: The Cho/Cr ratio was significantly higher in glial tumors grade II than in non-neoplastic lesions (p = 0.008) and in glial tumors grade III than in non-neoplastic lesions (p = 0.001). The Cho/NAA ratio was significantly higher in glial tumors grade II than in non-neoplastic lesions (p = 0.037). AADC/ADC between glial tumors grade II and glial tumors grade III showed a statistical significance (p = 0.023). CONCLUSION: Our study showed that 1H-MRS and apparent diffusion coefficients can help in evaluation and differentiation of solid brain lesions.

Intracranial yolk sac tumor in an adult patient: MRI, diffusion-weighted imaging and 1H MR spectroscopy features.

INTRODUCTION: Yolk sac tumors represent only 5%-7% of intracranial germ cell tumors, which comprise about 1% of all primary brain tumors in adults. Literature data about nonspecific imaging characteristics of these tumors are scant. We presented magnetic resonance imaging findings with diffusion-weighted imaging and proton magnetic resonance spectroscopy of this rare type of tumor in an adult patient. CASE REPORT: A 55-year-old man with progressive left side weakness, headache, dizziness and ataxia, underwent preoperative magnetic resonance imaging, diffusion-weighted imaging and proton magnetic resonance spectroscopy. After surgical resection and histological analysis, the final diagnosis of yolk sac tumor was established. Retrospective imaging analysis were performed in order to determine imaging and biochemical parameters that could be useful in the diagnostic evaluation of this tumor type. CONCLUSION: Though the imaging features of yolk sac tumor are not specific, morphoanatomical and metabolic imaging could offer the information that provides new insights into this tumor that may facilitate further therapeutic decision process and potentially provides better information regarding the disease prognosis.

The role of magnetic resonance imaging in the diagnosis of postoperative spondylodiscitis.

BACKGROUND: Spondylodiscitis, discitis associated with vertebral osteomyelitis may follow disc-removal surgery. A targeted successful treatment of spinal infections requires clinical and laboratory data that are completed by the contribution of imaging procedures. Neuroimaging provides precise information on correct topography, localization, propagation, and differential diagnosis of spinal infectious lesions. The aim of this study was to present magnetic resonance imaging (MRI) findings in patients with postoperative spondylodiscitis. METHODS: MRI was performed in 6 patients aged 29-50, with clinically suspected postoperative spondylodiscitis. Initial examination was performed 3-8 weeks after surgery and 3, 6, or 12 months after the treatment by antibiotics. Patients underwent MRI on a IT imaging unit (Siemens, Magnetom-Impact), including sagittal T1W and T2W images and axial T1W images before and after the administration of gadolinium contrast medium. RESULTS: MRI findings included: significantly decreased signal intensity with the loss of distinction between vertebral body and intervertebral disc space on T1W, increased signal intensity in the adjacent vertebral body and end-plates on T2W, contrast enhancement of vertebral body and disc space and paravertebral soft tissue changes. Follow-up examinations performed 3, 6, or 12 months after the treatment showed less abnormal signal intensities on both T1- and T2-weighted images. CONCLUSION: Postoperative spondylodiscitis is a rare but severe complication of lumbar disc surgery. Since conventional imaging techniques are not reliable for detecting spondylodiscitis in its early stages, MRI is of great significance in the diagnosis of postoperative spondylodiscitis.