Congenital melanocytic naevus syndrome and Dandy-Walker malformation - a mistaken association: case report and literature review.

Congenital melanocytic naevus (CMN) syndrome, previously termed neurocutaneous melanosis, is a rare disease caused by postzygotic mosaic mutations occurring during embryogenesis in precursors of melanocytes. The severity of neurological manifestations in CMN patients is related to central nervous system abnormalities found at magnetic resonance imaging. The association between CMN and Dandy-Walker malformation (DWM) has been described in the literature, but recent advances in imaging and genetics lead to diagnostic criteria revision. In this paper, we aim to re-evaluate the proposed association by reviewing the available literature and present a patient with CMN and a large posterior fossa cyst.

Cognitive trajectories in multiple sclerosis: a long-term follow-up study.

BACKGROUND: Cognitive impairment occurs in multiple sclerosis (MS) and undergoes a progressive worsening over disease course. However, clinicians still struggle to predict the course of cognitive function. To evaluate baseline clinical and imaging predictors of cognitive abilities worsening over time, we performed a latent trajectory analysis for cognitive performances in MS patients, up to 15 years from disease onset. METHODS: We collected age, sex, education, dominant and non-dominant 9-hole peg test (9HP) and timed 25-foot walk (T25-FW) as well as MRI measures (grey matter volume and lesion load) within 6 months from disease diagnosis for relapsing-remitting MS (RR-MS) patients. At diagnosis and over the follow-up, we also assessed cognitive status through the symbol digit modalities test (SDMT). Cognitive impairment was defined by applying age-, gender- and education-adjusted normative values. Group-based trajectory analysis was performed to determine trajectories, and the predictive value of clinical and imaging variables at baseline was assessed through multinomial logistic regression. RESULTS: We included 148 RR-MS (98 females and 50 males). Over 11 ± 4 year follow-up, 51.4% remained cognitively stable whereas 48.6% cognitively worsened. Cognitively worsening patients had a higher T25FW time (p = 0.004) and a reduced hippocampal volume at baseline (p = 0.04). CONCLUSION: Physical disability as well as hippocampal atrophy might depict patients at risk of cognitive worsening over the disease course. Therefore, using such predictors, clinicians may select patients to carefully evaluate for cognitive impairment as to eventually introduce cognitive rehabilitation treatments.

Cerebellar dysplasia related to PIK3CA mutation: a three-case series.

The term PROS (PIK3CA-Related Overgrowth Spectrum) indicates a wide spectrum of overgrowth disorders related to somatic mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) pathway. We present three cases with PIK3CA mutation and clinical characteristics encompassing MCAP (megalencephaly-capillary malformation) condition but lacking all criteria to a certain diagnosis, most of all showing prevalent and peculiar involvement of cerebellar structures at MRI (magnetic resonance imaging) mainly consisting in cortical rim thickening and abnormal orientation of folia axis. These cases expand the spectrum of intracranial MRI features in PIK3CA disorders.

Neuroimaging and neurodevelopmental outcome after early fetal growth restriction: NEUROPROJECT-FGR.

BACKGROUND: Adverse neurodevelopmental outcomes and MRI alterations are reported in infants born after fetal growth restriction (FGR). This study evaluates the additional role of FGR over prematurity in determining brain impairment. METHODS: Retrospective observational study comparing 48 FGR and 36 appropriate for gestational age infants born between 26 and 32 weeks' gestation who underwent a cerebral MRI at term equivalent age. Exclusion criteria were twins, congenital anomalies, and findings of overt brain lesions. Main outcomes were total maturation score (TMS) and cerebral areas independently measured by two neuro-radiologists and Griffiths or Bayley scale III scores at median age of 2 years. RESULTS: TMS was not significantly different between the groups. Inner calvarium and parenchyma's areas were significantly smaller in FGR cases. There were no significant differences in the average quotient scores. A positive correlation between parenchyma area and cognitive score was found (r = 0.372, p = 0.0078) and confirmed after adjusting for sex, gestational age, and birth weight (p = 0.0014). Among FGR, the subgroup with umbilical arterial Doppler velocimetry alterations had significantly worse gross motor scores (p = 0.005). CONCLUSIONS: FGR plays additional role over prematurity in determining brain impairment. An early structural dimensional MRI evaluation may identify infants who are at higher risk. IMPACT: Fetal growth-restricted infants showed smaller cerebral parenchymal areas than preterm controls. There is a positive correlation between the parenchyma area and the cognitive score. These results highlight the already known link between structure and function and add importance to the role of a structural dimensional MRI evaluation even in the absence of overt brain lesions.

Conventional MRI findings in hereditary degenerative ataxias: a pictorial review.

PURPOSE: Cerebellar ataxias are a large and heterogeneous group of disorders. The evaluation of brain parenchyma via MRI plays a central role in the diagnostic assessment of these conditions, being mandatory to exclude the presence of other underlying causes in determining the clinical phenotype. Once these possible causes are ruled out, the diagnosis is usually researched in the wide range of hereditary or sporadic ataxias. METHODS: We here propose a review of the main clinical and conventional imaging findings of the most common hereditary degenerative ataxias, to help neuroradiologists in the evaluation of these patients. RESULTS: Hereditary degenerative ataxias are all usually characterized from a neuroimaging standpoint by the presence, in almost all cases, of cerebellar atrophy. Nevertheless, a proper assessment of imaging data, extending beyond the mere evaluation of cerebellar atrophy, evaluating also the pattern of volume loss as well as concomitant MRI signs, is crucial to achieve a proper diagnosis. CONCLUSION: The integration of typical neuroradiological characteristics, along with patient's clinical history and laboratory data, could allow the neuroradiologist to identify some conditions and exclude others, addressing the neurologist to the more appropriate genetic testing.

Olfactory bulb enlargement in neurofibromatosis type 1: report of a novel finding.

Neurofibromatosis type 1 (NF1) is a genetic autosomal dominant disease caused by mutation of the protein neurofibromin, a regulator of cell growth. The most frequent intracranial findings are unidentified bright objects (UBOs), thickening of the corpus callosum, sphenoid wing dysplasia, cerebral vasculopathy, optic and non-optic pilocytic astrocytomas, and plexiform neurofibromas. We report two cases of NF1 patients with asymptomatic olfactory bulbs (OBs) enlargement depicted with Magnetic Resonance Imaging (MRI). To the best of our knowledge, this finding has not been reported in the scientific literature so far. We hypothesize that olfactory bulbs enlargement may have a pathogenetic nature like that of the UBOs as in one of our patients there was spontaneous regression during follow-up. The olfactory bulbs enlargement expands the broad neuroradiological spectrum of finding of NF1. More reports are required to better understand incidence, pathogenesis, and clinical behavior of olfactory bulbs enlargement in NF1 patients.

2D linear measures of ventricular enlargement may be relevant markers of brain atrophy and long-term disability progression in multiple sclerosis.

OBJECTIVES: Aim of this study was to investigate the reliability and validity of 2D linear measures of ventricular enlargement as indirect markers of brain atrophy and possible predictors of clinical disability. METHODS: In this retrospective longitudinal analysis of relapsing-remitting MS patients, brain volumes were computed at baseline and after 2 years. Frontal horn width (FHW), intercaudate distance (ICD), third ventricle width (TVW), and 4th ventricle width were obtained. Two-dimensional measures associated with brain volume at correlation analyses were entered in linear and logistic regression models testing the relationship with baseline clinical disability and 10-year confirmed disability progression (CDP), respectively. Possible cutoff values for clinically relevant atrophy were estimated via receiver operating characteristic (ROC) analyses and probed as 10-year CDP predictors using hierarchical logistic regression. RESULTS: Eighty-seven patients were available (61/26 = F/M; 34.1 ± 8.5 years). Moderate negative correlations emerged between ICD and TVW and normalized brain volume (NBV; p < 0.001) and percentage brain volume change per year (PBVC/y) and FHW, ICD, and TVW annual changes (p ≤ 0.005). Baseline disability was moderately associated with NBV, ICD, and TVW (p < 0.001), while PBVC/y predicted 10-year CDP (p = 0.01). A cutoff percentage ICD change per year (PICDC/y) value of 4.38%, corresponding to - 0.91% PBVC/y, correlated with 10-year CDP (p = 0.04). These estimated cutoff values provided extra value for predicting 10-year CDP (PBVC/y: p = 0.001; PICDC/y: p = 0.03). CONCLUSIONS: Two-dimensional measures of ventricular enlargement are reproducible and clinically relevant markers of brain atrophy, with ICD and its increase over time showing the best association with clinical disability. Specifically, a cutoff PICDC/y value of 4.38% could serve as a potential surrogate marker of long-term disability progression. KEY POINTS: • Assessment of ventricular enlargement as a rapidly accessible indirect marker of brain atrophy may prove useful in cases in which brain volume quantification is not practicable. • Two-dimensional linear measures of ventricular enlargement represent reliable, valid, and clinically relevant markers of brain atrophy. • A cutoff annualized percentage brain volume change of - 0.91% and the corresponding annualized percentage increase of 4.38% for intercaudate distance are able to discriminate patients who will develop long-term disability progression.

MRI features suggestive of gadolinium retention do not correlate with Expanded Disability Status Scale worsening in Multiple Sclerosis.

PURPOSE: Different studies showed correlations between gadolinium-based contrast agent (GBCA) administrations and dentate nucleus (DN) T1-weighted hyperintensity. The clinical impact of gadolinium retention, however, is still largely unknown. The aim of this study was to investigate relations between MRI and clinical disability in relapsing-remitting multiple sclerosis (RR-MS) patients. METHODS: In this retrospective study, clinical data were obtained from 74 RR-MS patients at baseline and after a mean follow-up time of 3.6 years, including the expanded disability status scale (EDSS) score and its change (ΔEDSS). Patients were considered showing clinical worsening if they score a ΔEDSS ≥ 1 (for baseline EDSS ≤ 5.5) or ΔEDSS ≥ 0.5 (for baseline EDSS > 5.5). From the MRI data, the presence of bilateral DN hyperintensity was recorded along with the calculation of longitudinal relaxation rate (R1) maps. RESULTS: Patients with DN hyperintensity showed similar ΔEDSS change compared to those without visible changes on T1-weighted images (p = 0.32). Similarly, no DN-R1 difference was found comparing stable patients with those showing a significant clinical worsening (p = 0.54). Finally, no significant effect of DN-R1 values explained the variance in ΔEDSS (p = 0.76), thus suggesting their independence from the clinical outcome. CONCLUSIONS: MS patients with DN hyperintensity show similar EDSS changes compared to subjects without DN high-signal intensity. Furthermore, mean DN-R1 values of patients with significant clinical worsening were comparable to those of stable subjects and were unrelated to clinical disability. Taken together, these findings suggest that gadolinium retention in the brain of MS patients does not affect their clinical worsening, expressed by the EDSS change.

The role of unidentified bright objects in the neurocognitive profile of neurofibromatosis type 1 children: a volumetric MRI analysis.

PURPOSE: Cognitive impairment is described in 80% of Neurofibromatosis type 1 (NF1) patients. Brain focal areas of T2w increased signal intensity on MRI, the so-called Unidentified Bright Objects (UBOs) have been hypothesized to be related to cognitive dysfunction, although conflicting results are available in literature. Here, we investigated the possible relation between UBOs' volume, cognitive impairment, and language disability in NF1 patients. MATERIAL AND METHODS: In this retrospective study, clinical and MRI data of 21 NF1 patients (M/F = 12/9; mean age 10.1 ± 4.5) were evaluated. Brain intellectual functioning and language abilities were assessed with specific scales, while the analyzed MRI sequences included axial 2D-T2-weighted and FLAIR sequences. These images were used independently for UBOs segmentation with a semiautomatic approach and obtained volumes were normalized for biparietal diameters to take into account for brain volume. Possible differences in terms of normalized UBOs volumes were probed between cognitively affected and preserved patients, as well as between subjects with or without language impairment. RESULTS: Patients cognitively affected were not different in terms of UBOs volume compared to those preserved (p = 0.35 and p = 0.30, for T2-weighted and FLAIR images, respectively). Similarly, no differences were found between patients with and without language impairment (p = 0.47 and p = 0.40, for the two sequences). CONCLUSIONS: The relation between UBOs and cognition in children with NF1 has been already investigated in literature, although leading to conflicting results. Our study expands the current knowledge, showing a lack of correlation between UBOs volume and both cognitive impairment and language disability in NF1 patients.

Segmentation methods applied to MRI-derived radiomic analysis for the prediction of placenta accreta spectrum in patients with placenta previa.

PURPOSE: To retrospectively evaluate the performance of different manual segmentation methods of placenta MR images for predicting Placenta Accreta Spectrum (PAS) disorders in patients with placenta previa (PP) using a Machine Learning (ML) Radiomics analysis. METHODS: 64 patients (n=41 with PAS and n= 23 without PAS) with PP who underwent MRI examination for suspicion of PAS were retrospectively selected. All MRI examinations were acquired on a 1.5 T using T2-weighted (T2w) sequences on axial, sagittal and coronal planes. Ten different manual segmentation methods were performed on sagittal placental T2-weighted images obtaining five sets of 2D regions of interest (ROIs) and five sets of 3D volumes of interest (VOIs) from each patient. In detail, ROIs and VOIs were positioned on the following areas: placental tissue, retroplacental myometrium, cervix, placenta with underneath myometrium, placenta with underneath myometrium and cervix. For feature stability testing, the same process was repeated on 30 randomly selected placental MRI examinations by two additional radiologists, working independently and blinded to the original segmentation. Radiomic features were extracted from all available ROIs and VOIs. 100 iterations of 5-fold cross-validation with nested feature selection, based on recursive feature elimination, were subsequently run on each ROI/VOI to identify the best-performing method to classify instances correctly. RESULTS: Among the segmentation methods, the best performance in predicting PAS was obtained by the VOIs covering the retroplacental myometrium (Mean validation score: 0.761, standard deviation: 0.116). CONCLUSION: Our preliminary results show that the VOI including the retroplacental myometrium using T2w images seems to be the best method when segmenting images for the development of ML radiomics predictive models to identify PAS in patients with PP.

Prostate Volume Estimation on MRI: Accuracy and Effects of Ellipsoid and Bullet-Shaped Measurements on PSA Density.

RATIONALE AND OBJECTIVES: PSA density (PSAd), an important decision-making parameter for patients with suspected prostate cancer (PCa), is dependent on magnetic resonance imaging prostate volume (PV) estimation. We aimed to compare the accuracy of the ellipsoid and bullet-shaped formulas with manual whole-gland segmentation as reference standard and to evaluate the corresponding PSAd diagnostic accuracy in predicting clinically significant PCa. MATERIALS AND METHODS: We retrospectively analysed 195 patients with suspected PCa who underwent magnetic resonance imaging and prostate biopsy. Patients with PCa were categorized according to ISUP score. PV and corresponding PSAd were calculated with manual segmentation (mPV and mPSAd) as well as with ellipsoid (ePV and ePSAd) and bullet-shaped (bPV and bPSAd) formulas. Inter and intra-reader reproducibility were assessed with Lin's concordance correlation coefficient and the intraclass correlation coefficient (ICC). A 2-way analysis of variance with post-hoc Bonferroni test was used for assessing PV differences. Predictive values of PSAd calculated with different methods for detecting clinically significant PCa were evaluated by receiver operating characteristic curve analysis and Youden's index. RESULTS: Both intra (ρ = 0.99, ICC = 0.99) and inter-reader (ρ = 0.98, ICC = 0.98) reproducibility were excellent. No significant difference was found between ePV and reference standard (p = 1.00). bPV was significantly different from both (p = 0.00). PSAd (mPSAd/ePSAd cut-off ≥ 0.15, bPSAd cut-off ≥ 0.12) had sensitivity = 69-70%, specificity = 72-75%, areas under the curve = 0.757-0.760 (p = 0.70-0.88). CONCLUSIONS: Our work shows that when using bullet-shaped formula, a different PSAd cut-off must be considered to avoid PCa under-diagnosis and inaccurate risk-stratification.

Spontaneous emphysematous osteomyelitis of the spine: A case report.

Spontaneous emphysematous osteomyelitis of the spine is a very rare but severe condition caused by gas-forming microorganisms. We present the case of a 41-year-old obese male patient presenting at the Emergency Department with diabetic ketoacidosis, fever, and difficulty in walking. computed tomography and magnetic resonance imaging of the spine revealed bone marrow edema and intraosseous gas collections at the level of the fourth and fifth lumbar metameres, suggesting an osteomyelitis sustained by gas-forming microorganisms, which was then confirmed by the isolation of Klebsiella pneumonia in blood culture. Imaging plays a central role for the diagnosis of emphysematous osteomyelitis: the presence of multiple intraosseous gas collections of variable size, especially in patients with specific risk factors, is highly suggestive of an infection caused by gas-forming pathogens. Being familiar with this peculiar neuroradiological appearance is essential to ensure an early diagnosis and a timely antimicrobial therapy, which can considerably ameliorate the prognosis.

Predictive factors of volumetric reduction in lumbar disc herniation treated by O2-O3 chemiodiscolysis.

PURPOSE: Aim of this study is to assess the effectiveness of O2-O3 percutaneous chemiodiscolysis by evaluating volumetric changes in lumbar disc herniation on magnetic resonance imaging, in order to identify possible pre-treatment factors affecting such changes Methods: Between January 2014 and December 2017, a total of 87 patients with low back pain and 103 lumbar disc herniations with MRI confirmation were considered for O2-O3 chemiodiscolysis. The volume of each herniated disc was determined before and after the treatment. RESULTS: Multiple linear regression analysis showed a strong correlation between post-treatment LDH volume percent change and both pre-treatment LDH volume and pre-treatment EQ-VAS (p<0.05), while age showed only a weak positive correlation with post-treatment LDH volume percent change (p<0.1). No association was found for other factors, such as sex and herniation disc level. CONCLUSIONS: In conclusion, age, baseline LDH volume and self-assessed disease severity score could represent three easy accessible outcome predictive parameters to consider when intradiscal O2-O3 chemiodiscolysis is envisaged. Better results after intradiscal O2-O3 chemiodiscolysis were obtained in older patients with higher pre-treatment LDH volume and low-moderate pre-treatment EQ-VAS.

Gut-liver axis and probiotics: their role in non-alcoholic fatty liver disease.

The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a "low bacterial richness" may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier ("leaky gut"), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.