CDKL5 deficiency disorder: progressive brain atrophy may be part of the syndrome.

The clinical phenotype of Cyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder (CDD) has been delineated but neuroimaging features have not been systematically analyzed. We studied brain magnetic resonance imaging (MRI) scans in a cohort of CDD patients and reviewed age at seizure onset, seizure semiology, head circumference. Thirty-five brain MRI from 22 unrelated patients were included. The median age at study entry was 13.4 years. In 14/22 patients (85.7%), MRI in the first year of life was unremarkable in all but two. In 11/22, we performed MRI after 24 months of age (range 2.5-23 years). In 8 out of 11 (72.7%), MRI showed supratentorial atrophy and in six cerebellar atrophy. Quantitative analysis detected volumetric reduction of the whole brain (-17.7%, P-value = 0.014), including both white matter (-25.7%, P-value = 0.005) and cortical gray matter (-9.1%, P-value = 0.098), with a reduction of surface area (-18.0%, P-value = 0.032), mainly involving the temporal regions, correlated with the head circumference (ρ = 0.79, P-value = 0.109). Both the qualitative structural assessment and the quantitative analysis detected brain volume reduction involving the gray and white matter. These neuroimaging findings may be related to either progressive changes due to CDD pathogenesis, or to the extreme severity of epilepsy, or both. Larger prospective studies are needed to clarify the bases for the structural changes we observed.

Effect of tumor genetics, pathology, and location on fMRI of language reorganization in brain tumor patients.

OBJECTIVES: Language reorganization may follow tumor invasion of the dominant hemisphere. Tumor location, grade, and genetics influence the communication between eloquent areas and tumor growth dynamics, which are drivers of language plasticity. We evaluated tumor-induced language reorganization studying the relationship of fMRI language laterality to tumor-related variables (grade, genetics, location), and patient-related variables (age, sex, handedness). METHODS: The study was retrospective cross-sectional. We included patients with left-hemispheric tumors (study group) and right-hemispheric tumors (controls). We calculated five fMRI laterality indexes (LI): hemispheric, temporal lobe, frontal lobe, Broca's area (BA), Wernicke's area (WA). We defined LI ≥ 0.2 as left-lateralized (LL) and LI < 0.2 as atypical lateralized (AL). Chi-square test (p < 0.05) was employed to identify the relationship between LI and tumor/patient variables in the study group. For those variables having significant results, confounding factors were evaluated in a multinomial logistic regression model. RESULTS: We included 405 patients (235 M, mean age: 51 years old) and 49 controls (36 M, mean age: 51 years old). Contralateral language reorganization was more common in patients than controls. The statistical analysis demonstrated significant association between BA LI and patient sex (p = 0.005); frontal LI, BA LI, and tumor location in BA (p < 0.001); hemispheric LI and fibroblast growth factor receptor (FGFR) mutation (p = 0.019); WA LI and O6-methylguanine-DNA methyltransferase promoter (MGMT) methylation in high-grade gliomas (p = 0.016). CONCLUSIONS: Tumor genetics, pathology, and location influence language laterality, possibly due to cortical plasticity. Increased fMRI activation in the right hemisphere was seen in patients with tumors in the frontal lobe, BA and WA, FGFR mutation, and MGMT promoter methylation. KEY POINTS: • Patients harboring left-hemispheric tumors present with contralateral translocation of language function. Influential variables for this phenomenon included frontal tumor location, BA location, WA location, sex, MGMT promoter methylation, and FGFR mutation. • Tumor location, grade, and genetics may influence language plasticity, thereby affecting both communication between eloquent areas and tumor growth dynamics. • In this retrospective cross-sectional study, we evaluated language reorganization in 405 brain tumor patients by studying the relationship of fMRI language laterality to tumor-related variables (grade, genetics, location), and patient-related variables (age, sex, handedness).

Neurologic outcome following liver transplantation for methylmalonic aciduria.

Liver and liver/kidney transplantation are increasingly used in methylmalonic aciduria, but little is known on their impact on CNS. The effect of transplantation on neurological outcome was prospectively assessed in six patients pre- and post-transplant by clinical evaluation and by measuring disease biomarkers in plasma and CSF, in combination with psychometric tests and brain MRI studies. Primary (methylmalonic- and methylcitric acid) and secondary biomarkers (glycine and glutamine) significantly improved in plasma, while they remained unchanged in CSF. Differently, biomarkers of mitochondrial dysfunction (lactate, alanine, and related ratios) significantly decreased in CSF. Neurocognitive evaluation documented significant higher post-transplant developmental/cognitive scores and maturation of executive functions corresponding to improvement of brain atrophy, cortical thickness, and white matter maturation indexes at MRI. Three patients presented post-transplantation reversible neurological events, which were differentiated, by means of biochemical and neuroradiological evaluations, into calcineurin inhibitor-induced neurotoxicity and metabolic stroke-like episode. Our study shows that transplantation has a beneficial impact on neurological outcome in methylmalonic aciduria. Early transplantation is recommended due to the high risk of long-term complications, high disease burden, and low quality of life.

Association of Lack of Speech Arrest During Cortical Stimulation With Interhemispheric Reorganization of the Functional Language Network in Patients With Brain Tumors.

BACKGROUND. Brain tumors induce language reorganization, which may influence the extent of resection in surgical planning. Direct cortical stimulation (DCS) allows definitive language mapping during awake surgery by locating areas of speech arrest (SA) surrounding the tumor. Although functional MRI (fMRI) combined with graph theory analysis can illustrate whole-brain network reorganization, few studies have corroborated these findings with DCS intraoperative mapping and clinical language performance. OBJECTIVE. We evaluated whether patients with low-grade gliomas (LGGs) without SA during DCS show increased right-hemispheric connections and better speech performance compared with patients with SA. METHODS. We retrospectively recruited 44 consecutive patients with left perisylvian LGG, preoperative language task-based fMRI, speech performance evaluation, and awake surgery with DCS. We generated language networks from ROIs corresponding to known language areas (i.e., language core) on fMRI using optimal percolation. Language core connectivity in the left and right hemispheres was quantified as fMRI laterality index (LI) and connectivity LI on the basis of fMRI activation maps and connectivity matrices. We compared fMRI LI and connectivity LI between patients with SA and without SA and used multivariable logistic regression (p < .05) to assess associations between DCS and connectivity LI, fMRI LI, tumor location, Broca area and Wernicke area involvement, prior treatments, age, handedness, sex, tumor size, and speech deficit before surgery, within 1 week after surgery, and 3-6 months after surgery. RESULTS. Patients with SA showed left-dominant connectivity; patients without SA lateralized more to the right hemisphere (p < .001). Between patients with SA and those without, fMRI LI was not significantly different. Patients without SA showed right-greater-than-left connectivity of Broca area and premotor area compared with patients with SA. Regression analysis showed significant association between no SA and right-lateralized connectivity LI (p < .001) and fewer speech deficits before (p < .001) and 1 week after (p = .02) surgery. CONCLUSION. Patients without SA had increased right-hemispheric connections and right translocation of the language core, suggesting language reorganization. Lack of interoperative SA was associated with fewer speech deficits both before and immediately after surgery. CLINICAL IMPACT. These findings support tumor-induced language plasticity as a compensatory mechanism, which may lead to fewer postsurgical deficits and allow extended resection.

Interpretable surface-based detection of focal cortical dysplasias: a Multi-centre Epilepsy Lesion Detection study.

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted 'gold-standard' subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.

3D CT-Inclusive Deep-Learning Model to Predict Mortality, ICU Admittance, and Intubation in COVID-19 Patients.

Chest CT is a useful initial exam in patients with coronavirus disease 2019 (COVID-19) for assessing lung damage. AI-powered predictive models could be useful to better allocate resources in the midst of the pandemic. Our aim was to build a deep-learning (DL) model for COVID-19 outcome prediction inclusive of 3D chest CT images acquired at hospital admission. This retrospective multicentric study included 1051 patients (mean age 69, SD = 15) who presented to the emergency department of three different institutions between 20th March 2020 and 20th January 2021 with COVID-19 confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Chest CT at hospital admission were evaluated by a 3D residual neural network algorithm. Training, internal validation, and external validation groups included 608, 153, and 290 patients, respectively. Images, clinical, and laboratory data were fed into different customizations of a dense neural network to choose the best performing architecture for the prediction of mortality, intubation, and intensive care unit (ICU) admission. The AI model tested on CT and clinical features displayed accuracy, sensitivity, specificity, and ROC-AUC, respectively, of 91.7%, 90.5%, 92.4%, and 95% for the prediction of patient's mortality; 91.3%, 91.5%, 89.8%, and 95% for intubation; and 89.6%, 90.2%, 86.5%, and 94% for ICU admission (internal validation) in the testing cohort. The performance was lower in the validation cohort for mortality (71.7%, 55.6%, 74.8%, 72%), intubation (72.6%, 74.7%, 45.7%, 64%), and ICU admission (74.7%, 77%, 46%, 70%) prediction. The addition of the available laboratory data led to an increase in sensitivity for patient's mortality (66%) and specificity for intubation and ICU admission (50%, 52%, respectively), while the other metrics maintained similar performance results. We present a deep-learning model to predict mortality, ICU admittance, and intubation in COVID-19 patients. KEY POINTS: • 3D CT-based deep learning model predicted the internal validation set with high accuracy, sensibility and specificity (> 90%) mortality, ICU admittance, and intubation in COVID-19 patients. • The model slightly increased prediction results when laboratory data were added to the analysis, despite data imbalance. However, the model accuracy dropped when CT images were not considered in the analysis, implying an important role of CT in predicting outcomes.

Single brain metastasis versus glioblastoma multiforme: a VOI-based multiparametric analysis for differential diagnosis.

PURPOSE: The authors' purpose was to create a valid multiparametric MRI model for the differential diagnosis between glioblastoma and solitary brain metastasis. MATERIALS AND METHODS: Forty-one patients (twenty glioblastomas and twenty-one brain metastases) were retrospectively evaluated. MRIs were analyzed with Olea Sphere® 3.0. Lesions' volumes of interest (VOIs) were drawn on enhanced 3D T1 MP-RAGE and projected on ADC and rCBV co-registered maps. Another two VOIs were drawn in the region of hyperintense cerebral edema, surrounding the lesion, respectively, within 5 mm around the enhancing tumor and into residual edema. Perfusion curves were obtained, and the value of signal recovery (SR) was reported. A two-sample T test was obtained to compare all parameters of GB and BM groups. Receiver operating characteristics (ROC) analysis was performed. RESULTS: According to ROC analysis, the area under the curve was 88%, 78% and 74%, respectively, for mean ADC VOI values of the solid component, the mean and max rCBV values in the perilesional edema and the PSR. The cumulative ROC curve of these parameters reached an area under the curve of 95%. Using perilesional max rCBV > 1.37, PSR > 75% and mean lesional ADC < 1 × 10-3 mm2 s-1 GB could be differentiated from solitary BM (sensitivity and specificity of 95% and 86%). CONCLUSION: Lower values of ADC in the enhancing tumor, a higher percentage of SR in perfusion curves and higher values of rCBV in the peritumoral edema closed to the lesion are strongly indicative of GB than solitary BM.

Reliability on multiband diffusion NODDI models: A test retest study on children and adults.

Neurite Orientation Dispersion and Density Imaging (NODDI) and Bingham-NODDI diffusion MRI models are nowadays very well-known models in the field of diffusion MRI as they represent powerful tools for the estimation of brain microstructure. In order to efficiently translate NODDI imaging findings into the diagnostic clinical practice, a test-retest approach would be useful to assess reproducibility and reliability of NODDI biomarkers, thus providing validation on precision of different fitting toolboxes. In this context, we conducted a test-retest study with the aim to assess the effects of different factors (i.e. fitting algorithms, multiband acceleration, shell configuration, age of subject and hemispheric side) on diffusion models reliability, assessed in terms of Intra-class Correlation Coefficient (ICC) and Variation Factor (VF). To this purpose, data from pediatric and adult subjects were acquired with Simultaneous-MultiSlice (SMS) imaging method with two different acceleration factor (AF) and four b-values, subsequently combined in seven shell configurations. Data were then fitted with two different GPU-based algorithms to speed up the analysis. Results show that each factor investigated had a significant effect on reliability of several diffusion parameters. Particularly, both datasets reveal very good ICC values for higher AF, suggesting that faster acquisitions do not jeopardize the reliability and are useful to decrease motion artifacts. Although very small reliability differences appear when comparing shell configurations, more extensive diffusion parameters variability results when considering shell configuration with lower b-values, especially for simple model like NODDI. Also fitting tools have a significant effect on reliability, but their difference occurs in both datasets and AF, so it appears to be independent from either misalignment and motion artifacts, or noise and SNR. The main achievement of the present study is to show how 10 min multi-shell diffusion MRI acquisition for NODDI acquisition can have reliable results in WM. More complex models do not appear to be more prone to less data acquisition as well as noisier data thus stressing the idea of Bingham-NODDI having greater sensitivity to true subject variability.

Multiparametric Imaging for Presurgical Planning of Craniopagus Twins: The Experience of Two Tertiary Pediatric Hospitals with Six Sets of Twins.

Conjoined twins are rare and pose a challenge to radiologists and surgeons. Craniopagus twins, where conjunction involves the cranium, are especially rare. Even in large pediatric centers, radiologists are unlikely to encounter more than one such event in their medical careers. This rarity makes it daunting to select a CT and MRI protocol for these infants. Using the experience of two tertiary pediatric hospitals with six sets of craniopagus twins, this multidisciplinary and multimodal integrated imaging approach highlights the key questions that need addressing in the decision-making process for possible surgical intervention.

Radiogenomics prediction for MYCN amplification in neuroblastoma: A hypothesis generating study.

BACKGROUND: MYCN amplification represents a powerful prognostic factor in neuroblastoma (NB) and may occasionally account for intratumoral heterogeneity. Radiomics is an emerging field of advanced image analysis that aims to extract a large number of quantitative features from standard radiological images, providing valuable clinical information. PROCEDURE: In this retrospective study, we aimed to create a radiogenomics model by correlating computed tomography (CT) radiomics analysis with MYCN status. NB lesions were segmented on pretherapy CT scans and radiomics features subsequently extracted using a dedicated library. Dimensionality reduction/features selection approaches were then used for features procession and logistic regression models have been developed for the considered outcome. RESULTS: Seventy-eight patients were included in this study, as training dataset, of which 24 presented MYCN amplification. In total, 232 radiomics features were extracted. Eight features were selected through Boruta algorithm and two features were lastly chosen through Pearson correlation analysis: mean of voxel intensity histogram (p = .0082) and zone size non-uniformity (p = .038). Five-times repeated three-fold cross-validation logistic regression models yielded an area under the curve (AUC) value of 0.879 on the training set. The model was then applied to an independent validation cohort of 21 patients, of which five presented MYCN amplification. The validation of the model yielded a 0.813 AUC value, with 0.85 accuracy on previously unseen data. CONCLUSIONS: CT-based radiomics is able to predict MYCN amplification status in NB, paving the way to the in-depth analysis of imaging based biomarkers that could enhance outcomes prediction.

Quantitative MRI-Based Analysis Identifies Developmental Limbic Abnormalities in PCDH19 Encephalopathy.

Protocadherin-19 (PCDH19) is a calcium dependent cell-adhesion molecule involved in neuronal circuit formation with prevalent expression in the limbic structures. PCDH19-gene mutations cause a developmental encephalopathy with prominent infantile onset focal seizures, variably associated with intellectual disability and autistic features. Diagnostic neuroimaging is usually unrevealing. We used quantitative MRI to investigate the cortex and white matter in a group of 20 PCDH19-mutated patients. By a statistical comparison between quantitative features in PCDH19 brains and in a group of age and sex matched controls, we found that patients exhibited bilateral reductions of local gyrification index (lGI) in limbic cortical areas, including the parahippocampal and entorhinal cortex and the fusiform and lingual gyri, and altered diffusivity features in the underlying white matter. In patients with an earlier onset of seizures, worse psychiatric manifestations and cognitive impairment, reductions of lGI and diffusivity abnormalities in the limbic areas were more pronounced. Developmental abnormalities involving the limbic structures likely represent a measurable anatomic counterpart of the reduced contribution of the PCDH19 protein to local cortical folding and white matter organization and are functionally reflected in the phenotypic features involving cognitive and communicative skills as well as local epileptogenesis.

Early alterations of cortical thickness and gyrification in migraine without aura: a retrospective MRI study in pediatric patients.

BACKGROUND: Migraine is the most common neurological disease, with high social-economical burden. Although there is growing evidence of brain structural and functional abnormalities in patients with migraine, few studies have been conducted on children and no studies investigating cortical gyrification have been conducted on pediatric patients affected by migraine without aura. METHODS: Seventy-two pediatric patients affected by migraine without aura and eighty-two controls aged between 6 and 18 were retrospectively recruited with the following inclusion criteria: MRI exam showing no morphological or signal abnormalities, no systemic comorbidities, no abnormal neurological examination. Cortical thickness (CT) and local gyrification index (LGI) were obtained through a dedicated algorithm, consisting of a combination of voxel-based and surface-based morphometric techniques. The statistical analysis was performed separately on CT and LGI between: patients and controls; subgroups of controls and subgroups of patients. RESULTS: Patients showed a decreased LGI in the left superior parietal lobule and in the supramarginal gyrus, compared to controls. Female patients presented a decreased LGI in the right superior, middle and transverse temporal gyri, right postcentral gyrus and supramarginal gyrus compared to male patients. Compared to migraine patients younger than 12 years, the ≥ 12-year-old subjects showed a decreased CT in the superior and middle frontal gyri, pre- and post-central cortex, paracentral lobule, superior and transverse temporal gyri, supramarginal gyrus and posterior insula. Migraine patients experiencing nausea and/or vomiting during headache attacks presented an increased CT in the pars opercularis of the left inferior frontal gyrus. CONCLUSIONS: Differences in CT and LGI in patients affected by migraine without aura may suggest the presence of congenital and acquired abnormalities in migraine and that migraine might represent a vast spectrum of different entities. In particular, ≥ 12-year-old pediatric patients showed a decreased CT in areas related to the executive function and nociceptive networks compared to younger patients, while female patients compared to males showed a decreased CT of the auditory cortex compared to males. Therefore, early and tailored therapies are paramount to obtain migraine control, prevent cerebral reduction of cortical thickness and preserve executive function and nociception networks to ensure a high quality of life.

Microcephalic osteodysplastic primordial dwarfism type II and pachygyria: Morphometric analysis in a 2-year-old girl.

Microcephalic osteodysplastic primordial dwarfism (MOPD) type II is a rare disorder characterized by skeletal dysplasia, severe proportionate short stature, insulin resistance and cerebrovascular abnormalities including cerebral aneurysms and moyamoya disease. MOPD type II is caused by mutations in the pericentrin (PCNT) gene, which encodes a protein involved in centrosomes function. We report a 2 year old girl affected by MOPD type II caused by two compound heterozygous loss-of-function variants in PCNT gene, of which one is a novel variant (c.5304delT; p.Gly1769AlafsTer34). The patient presented atypical brain magnetic resonance imaging (MRI) findings consistent with pachygyria. This was confirmed by morphometric analysis of cortical thickness (CT) and gyrification index by comparing MRI data of the patient with a group of eight age-matched healthy controls. The statistical analysis revealed a significant and diffuse increase of CT with an anterior-predominant pattern and diffuse reduced gyrification (p < .05). These findings provide new evidences to the emergent concept that malformations of cortical development are complex disorders and that new genetic findings contribute to the fading of classification borders.

Developmental and epileptic encephalopathy due to SZT2 genomic variants: Emerging features of a syndromic condition.

Seizure threshold 2 (SZT2) gene mutations have been associated with developmental and epileptic encephalopathies (DEEs). Following a literature review, we collected 22 patients and identified the main clinical features related to SZT2 variants that are epilepsy with onset within the first years of life, intellectual disability (ID), macrocephaly with dysmorphic facial features, corpus callosum (CC) shape abnormalities, and cortical migration disorders. Moreover, we identified the c.7825T>G homozygous missense variant in SZT2 in two female siblings presenting with focal seizures, mild-moderate ID, behavioral disturbances, and facial dysmorphisms. Interictal Electroencephalogram (EEG) and ictal EEG were both informative and revealed, respectively, temporal bilateral asynchronous slow and epileptiform abnormalities and a focal onset in both of them. Neuroimaging study revealed a thick and abnormally shaped CC. Seizure threshold 2 has been identified as a component of the KICSTOR complex, a newly recognized protein complex involved in the mammalian target of rapamycin (mTOR) pathway. mTOR signaling dysregulation represents common pathogenetic mechanisms that can explain the presence of both epileptogenesis and ID. Even if few cases had been reported, a new clinical phenotype is emerging, and recent hypothesis of hyperactivation of mTORC1 signaling might also open to targeted treatments, challenging an early diagnosis as of paramount importance.

Visual pathways evaluation in Kearns Sayre syndrome: a diffusion tensor imaging study.

PURPOSE: Kearns Sayre syndrome (KSS) is a mitochondrial disorder characterized by development of visual impairment. Electroretinogram (ERG) and visual evoked potentials are not able to provide topographical information of optic damage. The purpose of this study was to explore retrochiasmatic optic pathway alteration in KSS with diffusion tractographic analysis and to compare it with different tracts. METHODS: DTI from 8 KSS subjects (14.7 years) and 10 healthy controls (HC) were acquired on a 3T scanner. Optic radiations (OR), optic tracts (OT), inferior frontooccipital fasciculus (IFOF) and corticospinal tract (CST) were reconstructed with probabilistic tractography. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial (RD), and axial diffusivity (AD) were calculated, evaluating group differences. T test on diffusion parameters identified significantly different track portions among cohorts. RESULTS: All patients had optic pathway alterations at electrophysiological examination. Significant lower FA were found in OT, IFOF, and CST of KSS group. RD was significantly higher in bilateral OR, IFOF, CST, and right OT, while ADC was higher in bilateral OR and CST. RD values were higher in the proximal and distal portion of OR bilaterally and in the distal portion of right OT, while widespread differences were found in IFOF and CST. No significant differences were found for AD. FA profiles analysis demonstrated significant differences between groups in several regions of OT, IFOF, and CST, while ADC assessment revealed spread differences in OR and CST. CONCLUSIONS: DTI evaluation of retrochiasmatic tracks may represent a useful tool to topographically investigate retrochiasmatic visual impairment in KSS.

Correction to: Spinal cord involvement in Kearns-Sayre syndrome: a neuroimaging study.

The original article was published with an incorrect presentation of all author names.

Dentate nucleus T1 hyperintensity: is it always gadolinium all that glitters?

In the last few years, several scientific papers and reports have demonstrated magnetic resonance (MR) signal intensity (SI) changes on pre-contrast T1-weighted images following multiple gadolinium-based contrast agents (GBCA) administrations, particularly following the exposure to linear GBCAs. Pathological animal and human post-mortem studies have confirmed the relationship between this radiological finding and the presence of gadolinium accumulation in vulnerable brain regions in patients with normal renal function. In this short communication, we report the case of a 15-year-old patient affected by b-cell acute lymphoblastic leukemia (bALL) who developed a hyperintense signal in the dentate nuclei following multiple administrations of a macrocyclic GBCA. The purpose of this report is to discuss possible differential diagnoses of this radiological finding with special focus on the differentiation between iron or manganese accumulation, post-irradiation changes and GBCA-related Gd deposition, highlighting the importance of the acquisition of accurate clinical data to improve our scientific knowledge.

Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children.

BACKGROUND: Few studies have been conducted on the relations between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. OBJECTIVE: The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. MATERIALS AND METHODS: This retrospective study included 50 patients, mean age: 8 years (standard deviation: 4.8 years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naïve patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus-to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P-values were considered significant if <0.05. RESULTS: A significant effect of the number of GBCA administrations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). CONCLUSION: Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children.

Magnetic resonance imaging patterns of treatment-related toxicity in the pediatric brain: an update and review of the literature.

Treatment-related neurotoxicity is a potentially life-threatening clinical condition that can represent a diagnostic challenge. Differentiating diagnoses between therapy-associated brain injury and recurrent disease can be difficult, and the immediate recognition of neurotoxicity is crucial to providing correct therapeutic management, ensuring damage reversibility. For these purposes, the knowledge of clinical timing and specific treatment protocols is extremely important for interpreting MRI patterns. Neuroradiologic findings are heterogeneous and sometimes overlapping, representing the compounding effect of the different treatments. Moreover, MRI patterns can be acute, subacute or delayed and involve different brain regions, depending on (1) the mechanism of action of the specific medication and (2) which brain regions are selectively vulnerable to specific toxic effects. This review illustrates the most common radiologic appearance of radiotherapy, chemotherapy and medication-associated brain injury in children, with special focus on the application of advanced MRI techniques (diffusion, perfusion and proton spectroscopy) in the diagnosis of the underlying processes leading to brain toxicity.

The impact of vision on the dynamic characteristics of the gait: strategies in children with blindness.

Visually impaired persons present an atypical gait pattern characterized by slower walking speed, shorter stride length and longer time of stance. Three explanatory hypotheses have been advanced in the literature: balance deficit, lack of an anticipatory mechanisms and foot probing the ground. In the present study, we compared the three hypotheses by applying their predictions to gait analysis and posturography of blind children without neurological impairment and compared their performance with that of an age-matched control group. The gait analysis results documented that blind children presented reduced walking velocity and step length, increased step width and external rotation of the foot progression angle, reduced ground reaction force and ankle maximum angle, moment and power in late stance, increased head flexion, decreased thorax flexion and pelvis anteversion, compared with the control group. The posturographic analysis showed equal skill level between blind children and normally sighted children when they close their eyes. The results are consistent with only one of the three hypotheses: namely, they prove that blind children's gait is influenced only by the absence of visually driven anticipatory control mechanisms. Finally, rehabilitative recommendations for children with blindness are advanced in discussion.