Diffuse White Matter Abnormalities Research Articles

Current clinical presentations of AIDS dementia in a tropical environment: study of 26 observations in the neurology department of the University Hospital of Conakry

IntroductionIn sub-Saharan Africa (SSA), the clinical and progressive diagnostic certainty of AIDS dementia is difficult to establish due to under-medicalization and delays in consultation and especially the diversity of etiologies of demented states.Material and methodsWe carried out a retrospective study of 196 patients hospitalized for dementia syndrome between 2016 and 2021 in the neurology department of the University Hospital of Conakry.The criteria labeled in this study are those retained by the DSM-IV and the classification of the American Academy of Neurology (AAN) developed in accordance with the WHO.ResultsHIV etiology was identified in patients aged 44–67 years (17 women and 19 men). The clinical picture was dominated by severe cognitive disorders, slowed ideation, memory disorders and reduced motor skills associated with personality changes. Neurological examination revealed dysphoric disorders in most patients, sphincter abnormalities in 13 cases and labio-lingual tremor in 11 cases. Diagnosis was based on positive serological tests for HIV1 antibodies (25 cases) and HIV2 antibodies (1 case) using the Elisa and Western blot techniques, and the presence of discretely hypercellular CSF. Magnetic resonance imaging contributed to the diagnosis, showing diffuse white matter abnormalities with hyper signals on T2-weighted or FLAIR sequences.ConclusionThis study shows a non-stereotype clinical picture of AIDS dementia requiring a differential diagnosis with other infectious dementias. These results are important for the therapeutic and prognostic discussion.

Subacute Partially Reversible Leukoencephalopathy Expands the Aicardi-Goutières Syndrome Phenotype.

To report a series of atypical presentations of Aicardi-Goutières syndrome. Clinical, neuroimaging, and genetic data. We report a series of six unrelated patients (five males) with a subacute loss of developmental milestones, pyramidal signs, and regression of communication abilities, with onset at ages ranging from 7 to 20 months, reaching a nadir after 4 to 24 weeks. A remarkable improvement of lost abilities occurred in the follow-up, and they remained with residual spasticity and dysarthria but preserved cognitive function. Immunization or febrile illness occurred before disease onset in all patients. CSF was normal in two patients, and in four, borderline or mild lymphocytosis was present. A brain CT scan disclosed a subtle basal ganglia calcification in one of six patients. Brain MRI showed asymmetric signal abnormalities of white matter with centrum semi-ovale involvement in five patients and a diffuse white matter abnormality with contrast enhancement in one. Four patients were diagnosed and treated for acute demyelinating encephalomyelitis (ADEM). Brain imaging was markedly improved with one year or more of follow-up (average of 7 years), but patients remained with residual spasticity and dysarthria without cognitive impairment. Demyelination relapse occurred in a single patient four years after the first event. Whole-exome sequencing (WES) was performed in all patients: four of them disclosed biallelic pathogenic variants in RNASEH2B (three homozygous p.Ala177Thr and one compound heterozygous p.Ala177Thr/p.Gln58*) and in two of them the same homozygous deleterious variants in RNASEH2A (p.Ala249Val). This report expands the phenotype of AGS to include subacute developmental regression with partial clinical and neuroimaging improvement. Those clinical features might be misdiagnosed as ADEM.

Prenatal tobacco smoke exposure and risk of brain abnormalities on magnetic resonance imaging at term in infants born very preterm

Prenatal tobacco smoke exposure and preterm birth are associated with abnormal brain and neurodevelopmental outcomes in infants. Studies that can disentangle indirect mediating effects from direct effects of prenatal tobacco smoke exposure on sensitive early brain magnetic resonance imaging biomarkers in very preterm infants are needed. This study aimed to determine whether prenatal tobacco smoke exposure in preterm infants posed any direct effects on magnetic resonance imaging-determined global brain abnormality score and secondary measures of brain abnormalities after removing any indirect mediating effects of preterm birth on neurostructural outcomes. We examined brain magnetic resonance imaging findings collected at 39 to 44 weeks postmenstrual age from a prospective cohort of 395 infants born very preterm (gestational age of ≤32 weeks). The primary outcome was global brain abnormality score, and the secondary outcomes were global efficiency of structural connectome, diffuse white matter abnormality volume, total brain tissue volume, total gray and white matter volumes, and cerebellar volume. Maternal reports of smoking during pregnancy were obtained. We performed multivariable linear regression analyses to examine the association between prenatal tobacco smoke exposure and our magnetic resonance imaging outcomes, controlling for prospectively collected confounders. Moreover, we performed a mediation analysis to estimate the direct effects of prenatal tobacco smoke exposure on brain abnormalities and any indirect effects through preterm birth. Overall, 12.6% of infants had prenatal tobacco smoke exposure. Infants with prenatal tobacco smoke exposure had a higher median global brain abnormality score than nonexposed infants (7 [interquartile range, 0-41] vs 5 [interquartile range, 0-34]; P≤.001); the findings remained significant (P<.001) after controlling for antenatal confounders. Global efficiency (P<.001), diffuse white matter volume (P=.037), and total brain tissue volume (P=.047) were significantly different between TSE groups in multivariable analyses. On mediation analysis, preterm birth mediated between 0% and 29% of the indirect effect of prenatal tobacco smoke exposure on several measures of brain abnormality outcomes. Thus, prenatal tobacco smoke exposure had a direct adverse effect between 71% and 100% on brain injury or abnormal development. Our study has identified multiple adverse effects of prenatal tobacco smoke exposure on sensitive and objective measures of neonatal brain injury and abnormal development; most cases seemed to be a direct effect of prenatal tobacco smoke exposure on fetal brain development. The results underscored the significant adverse neurostructural effects of prenatal tobacco smoke exposure to tobacco smoke pollutants.

Diffuse excessive high signal intensity in the preterm brain on advanced MRI represents widespread neuropathology

Preterm brains commonly exhibit elevated signal intensity in the white matter on T2-weighted MRI at term-equivalent age. This signal, known as diffuse excessive high signal intensity (DEHSI) or diffuse white matter abnormality (DWMA) when quantitatively assessed, is associated with abnormal microstructure on diffusion tensor imaging. However, postmortem data are largely lacking and difficult to obtain, and the pathological significance of DEHSI remains in question. In a cohort of 202 infants born preterm at ≤32 weeks gestational age, we leveraged two newer diffusion MRI models – Constrained Spherical Deconvolution (CSD) and neurite orientation dispersion and density index (NODDI) – to better characterize the macro and microstructural properties of DWMA and inform the ongoing debate around the clinical significance of DWMA. With increasing DWMA volume, fiber density broadly decreased throughout the white matter and fiber cross-section decreased in the major sensorimotor tracts. Neurite orientation dispersion decreased in the centrum semiovale, corona radiata, and temporal lobe. These findings provide insight into DWMA's biological underpinnings and demonstrate that it is a serious pathology.

Superficial and deep white matter diffusion abnormalities in focal epilepsies.

This study was undertaken to evaluate superficial-white matter (WM) and deep-WM magnetic resonance imaging diffusion tensor imaging (DTI) metrics and identify distinctive patterns of microstructural abnormalities in focal epilepsies of diverse etiology, localization, and response to antiseizure medication (ASM). We examined DTI data for 113 healthy controls and 113 patients with focal epilepsies: 51 patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) refractory to ASM, 27 with pharmacoresponsive TLE-HS, 15 with temporal lobe focal cortical dysplasia (FCD), and 20 with frontal lobe FCD. To assess WM microstructure, we used a multicontrast multiatlas parcellation of DTI. We evaluated fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), and assessed within-group differences ipsilateral and contralateral to the epileptogenic lesion, as well as between-group differences, in regions of interest (ROIs). The TLE-HS groups presented more widespread superficial- and deep-WM diffusion abnormalities than both FCD groups. Concerning superficial WM, TLE-HS groups showed multilobar ipsilateral and contralateral abnormalities, with less extensive distribution in pharmacoresponsive patients. Both the refractory TLE-HS and pharmacoresponsive TLE-HS groups also presented pronounced changes in ipsilateral frontotemporal ROIs (decreased FA and increased MD, RD, and AD). Conversely, FCD patients showed diffusion changes almost exclusively adjacent to epileptogenic areas. Our findings add further evidence of widespread abnormalities in WM diffusion metrics in patients with TLE-HS compared to other focal epilepsies. Notably, superficial-WM microstructural damage in patients with FCD is more restricted around the epileptogenic lesion, whereas TLE-HS groups showed diffuse WM damage with ipsilateral frontotemporal predominance. These findings suggest the potential of superficial-WM analysis for better understanding the biological mechanisms of focal epilepsies, and identifying dysfunctional networks and their relationship with the clinical-pathological phenotype. In addition, lobar superficial-WM abnormalities may aid in the diagnosis of subtle FCDs.

Leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) case report: diagnosis and management of a rare neurological disease

BackgroundLeukoencephalopathy with brain calcifications and cysts (LCC; also known as Labrune syndrome) is a rare genetic microangiopathy caused by biallelic mutations in SNORD118. The mechanisms by which loss-of-function mutations in SNORD118 lead to the phenotype of leukoencephalopathy, calcifications and intracranial cysts is unknown.Case presentationWe present the histopathology of a 36-year-old woman with ataxia and neuroimaging findings of diffuse white matter abnormalities, cerebral calcifications, and parenchymal cysts, in whom the diagnosis of LCC was confirmed with genetic testing. Biopsy of frontal white matter revealed microangiopathy with small vessel occlusion and sclerosis associated with axonal loss within the white matter.ConclusionsThese findings support that the white matter changes seen in LCC arise as a consequence of ischemia rather than demyelination.

White matter diffusion abnormalities observed in cognitively normal elderly before conversion to mild cognitive impairment

AbstractBackgroundDifferences in white matter (WM) microstructure, as measured with diffusion tensor imaging (DTI), have been observed between cognitively normal, mild cognitively impaired (MCI), and Alzheimer’s disease (AD) patient groups. With increased focus on early intervention for AD, detection of preclinical changes is paramount; however, due to difficulties in predicting future conversion, few studies have investigated WM deterioration prior to symptom onset. Using DTI data from the Vallecas project (an 8‐year longitudinal study of healthy elderly individuals), we determine if WM changes can be found in cognitively normal individuals before conversion to MCI.MethodsFrom a baseline cohort of 824 cognitively normal 70‐85 year olds, 65 individuals converted to MCI over the study duration (mean age 77.0±4.29 years, 58% female). 65 non‐converters were matched by age, sex, and years of education to act as controls. DTI scans from one year before conversion were analysed using tract‐based spatial statistics implemented in FSL. Fractional anisotropy (FA), mean diffusivity (MD), and mode of anisotropy (MO) were compared between groups using non‐parametric permutation tests. A second comparison between future converters and all 759 non‐converters (mean age 74.0±3.92 years, 65% female) was also conducted, using age, sex, and years of education as covariates.ResultsIn the unmatched comparisons, controls had higher FA in the left forceps minor (ForMin) and anterior corona radiata (CR) (p&lt;0.05), and higher MO along the corpus callosum (CC) and ForMin (p&lt;0.01). Future converters had higher FA in the left posterior CR and corticospinal tract (p&lt;0.05), higher MD in the left anterior CR (p&lt;0.05), and higher MO along the bilateral projection fibres (p&lt;0.01). In the matched comparison, only MO differences were observed, with higher MO in controls along the body of the CC (p&lt;0.05), and higher MO in future converters in the left projection fibres and the splenium of the CC (p&lt;0.01). All significant results were FWE‐corrected.ConclusionsOur results suggest that frontal commissural fibres begin to deteriorate in cognitively normal subjects destined to convert to MCI, whilst also demonstrating selective preservation of projection fibres. We also find that MO is a sensitive measure of white matter microstructural changes presaging cognitive decline, even in preclinical populations.

Advanced neuroimaging techniques in epilepsy.

We review significant advances in epilepsy imaging in recent years. Structural MRI at 7T with optimization of acquisition and postacquisition image processing increases the diagnostic yield but artefactual findings remain a challenge. MRI analysis from multiple sites indicates different atrophy patterns and white matter diffusion abnormalities in temporal lobe and generalized epilepsies, with greater abnormalities close to the presumed seizure source. Structural and functional connectivity relate to seizure spread and generalization; longitudinal studies are needed to clarify the causal relationship of these associations. Diffusion MRI may help predict surgical outcome and network abnormalities extending beyond the epileptogenic zone. Three-dimensional multimodal imaging can increase the precision of epilepsy surgery, improve seizure outcome and reduce complications. Language and memory fMRI are useful predictors of postoperative deficits, and lead to risk minimization. FDG PET is useful for clinical studies and specific ligands probe the pathophysiology of neurochemical fluxes and receptor abnormalities. Improved structural MRI increases detection of abnormalities that may underlie epilepsy. Diffusion, structural and functional MRI indicate the widespread associations of epilepsy syndromes. These can assist stratification of surgical outcome and minimize risk. PET has continued utility clinically and for research into the pathophysiology of epilepsies.

Identification of a Rare Case With Nagashima-Type Palmoplantar Keratoderma and 18q Deletion Syndrome via Exome Sequencing and Low-Coverage Whole-Genome Sequencing.

Nagashima-type palmoplantar keratoderma (NPPK) is characterized by non-progressive, diffuse, and cross-gradient hyperkeratosis caused by mutations in the SERPINB7 gene on chromosome 18q21.33. Chromosome 18q deletion syndrome (18q- syndrome) is a terminal deletion or microdeletion syndrome characterized by intellectual disability and congenital malformations. This paper describes an 18-year-old man with palmoplantar keratoderma and diffuse white matter abnormalities in the brain. Trio-based exome sequencing (ES) revealed a suspected mosaic compound heterozygous mutation for c.796C>T (p.Arg266∗) in exon 8 inherited from the mother and a de novo exons 4–6 deletion of SERPINB7. Additional copy number variant (CNV) analysis of the ES data indicated a heterozygous gross deletion of 18q22.3-q23. The two SERPINB7 gene variants were verified by Sanger sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Finally, low-coverage whole-genome sequencing (WGS) confirmed the 18q22.3-q23 deletion and additionally detected a mosaic 18q21.33-q22.3 deletion, together explaining NPPK and the neurological phenotypes of the proband. The gross deletion of all exons of SERPINB7 was revealed for the first time. More rarely, c.796C>T (p.Arg266∗) was likely to be mosaic, while the exon deletion was mosaic. In conclusion, the combination of multiple molecular genetic testing methods provides comprehensive informative molecular findings and promotes the diagnosis of complex diseases, as in this case.

Heterogeneity of cellular inflammatory responses in ageing white matter and relationship to Alzheimer's and small vessel disease pathologies.

White matter lesions (WML) are common in the ageing brain, often arising in a field effect of diffuse white matter abnormality. Although WML are associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD), their cause and pathogenesis remain unclear. The current study tested the hypothesis that different patterns of neuroinflammation are associated with SVD compared to AD neuropathology by assessing the immunoreactive profile of the microglial (CD68, IBA1 and MHC‐II) and astrocyte (GFAP) markers in ageing parietal white matter (PARWM) obtained from the Cognitive Function and Ageing Study (CFAS), an ageing population‐representative neuropathology cohort. Glial responses varied extensively across the PARWM with microglial markers significantly higher in the subventricular region compared to either the middle‐zone (CD68 p = 0.028, IBA1 p < 0.001, MHC‐II p < 0.001) or subcortical region (CD68 p = 0.002, IBA1 p < 0.001, MHC‐II p < 0.001). Clasmatodendritic (CD) GFAP+ astrocytes significantly increased from the subcortical to the subventricular region (p < 0.001), whilst GFAP+ stellate astrocytes significantly decreased (p < 0.001). Cellular reactions could be grouped into two distinct patterns: an immune response associated with MHC‐II/IBA1 expression and CD astrocytes; and a more innate response characterised by CD68 expression associated with WML. White matter neuroinflammation showed weak relationships to the measures of SVD, but not to the measures of AD neuropathology. In conclusion, glial responses vary extensively across the PARWM with diverse patterns of white matter neuroinflammation. Although these findings support a role for vascular factors in the pathogenesis of age‐related white matter neuroinflammation, additional factors other than SVD and AD pathology may drive this. Understanding the heterogeneity in white matter neuroinflammation will be important for the therapeutic targeting of age‐associated white matter damage.

Automatic Segmentation of Diffuse White Matter Abnormality on T2-weighted Brain MR Images Using Deep Learning in Very Preterm Infants.

About 50%-80% of very preterm infants (VPIs) (≤ 32 weeks gestational age) exhibit diffuse white matter abnormality (DWMA) on their MR images at term-equivalent age. It remains unknown if DWMA is associated with developmental impairments, and further study is warranted. To aid in the assessment of DWMA, a deep learning model for DWMA quantification on T2-weighted MR images was developed. This secondary analysis of prospective data was performed with an internal cohort of 98 VPIs (data collected from December 2014 to April 2016) and an external cohort of 28 VPIs (data collected from January 2012 to August 2014) who had already undergone MRI at term-equivalent age. Ground truth DWMA regions were manually annotated by two human experts with the guidance of a prior published semiautomated algorithm. In a twofold cross-validation experiment using the internal cohort of 98 infants, the three-dimensional (3D) ResU-Net model accurately segmented DWMA with a Dice similarity coefficient of 0.907 ± 0.041 (standard deviation) and balanced accuracy of 96.0% ± 2.1, outperforming multiple peer deep learning models. The 3D ResU-Net model that was trained with the whole internal cohort (n = 98) was further tested on an independent external test cohort (n = 28) and achieved a Dice similarity coefficient of 0.877 ± 0.059 and balanced accuracy of 92.3% ± 3.9. The externally validated 3D ResU-Net deep learning model for accurately segmenting DWMA may facilitate the clinical diagnosis of DWMA in VPIs. Supplemental material is available for this article. Keywords: Brain/Brain Stem, Convolutional Neural Network (CNN), MR-Imaging, Pediatrics, Segmentation, Supervised learning © RSNA, 2021.

Diffuse white matter abnormality in very preterm infants at term reflects reduced brain network efficiency

Between 50 and 80% of very preterm infants (<32 weeks gestational age) exhibit increased white matter signal intensity on T2-weighted MRI at term-equivalent age, known as diffuse white matter abnormality (DWMA). A few studies have linked DWMA with microstructural abnormalities, but the exact relationship remains poorly understood. We related DWMA extent to graph theory measures of network efficiency at term in a representative cohort of 343 very preterm infants. We performed anatomic and diffusion MRI at term and quantified DWMA volume with our novel, semi-automated algorithm. From diffusion-weighted structural connectomes, we calculated the graph theory metrics local efficiency and clustering coefficient, which measure the ability of groups of nodes to perform specialized processing, and global efficiency, which assesses the ability of brain regions to efficiently combine information. We computed partial correlations between these measures and DWMA volume, adjusted for confounders. Increasing DWMA volume was associated with decreased global efficiency of the entire very preterm brain and decreased local efficiency and clustering coefficient in a variety of regions supporting cognitive, linguistic, and motor function. We show that DWMA is associated with widespread decreased brain network efficiency, suggesting that it is pathologic and likely has adverse developmental consequences.

Perinatal Risk and Protective Factors in the Development of Diffuse White Matter Abnormality on Term-Equivalent Age Magnetic Resonance Imaging in Infants Born Very Preterm

To identify perinatal clinical diseases and treatments that are associated with the development of objectively diagnosed diffuse white matter abnormality (DWMA) on structural magnetic resonance imaging (MRI) at term-equivalent age in infants born very preterm. A prospective cohort of 392 infants born very preterm (≤32weeks of gestational age) was enrolled from 5 level III/IV neonatal intensive care units between September 2016 and November 2019. MRIs of the brain were collected at 39 to 45weeks of postmenstrual age to evaluate DWMA volume. A predefined list of pertinent maternal characteristics, pregnancy/delivery data, and neonatal intensive care unit data were collected for enrolled patients to identify antecedents of objectively diagnosed DWMA. Of the 392 infants in the cohort, 377 (96%) had high-quality MRI data. Their mean (SD) gestational age was 29.3 (2.5) weeks. In multivariable linear regression analyses, pneumothorax (P=.027), severe bronchopulmonary dysplasia (BPD) (P=.009), severe retinopathy of prematurity (P<.001), and male sex (P=.041) were associated with increasing volume of DWMA. The following factors were associated with decreased risk of DWMA: postnatal dexamethasone therapy for severe BPD (P=.004), duration of caffeine therapy for severe BPD (P=.009), and exclusive maternal milk diet at neonatal intensive care unit discharge (P=.049). Severe retinopathy of prematurity and BPD exhibited the strongest adverse association with development of DWMA. We also identified treatments and nutritional factors that appear protective against the development of DWMA that also have implications for the clinical care of infants born very preterm.

Novel diffuse white matter abnormality biomarker at term-equivalent age enhances prediction of long-term motor development in very preterm children

Our objective was to evaluate the independent prognostic value of a novel MRI biomarker—objectively diagnosed diffuse white matter abnormality volume (DWMA; diffuse excessive high signal intensity)—for prediction of motor outcomes in very preterm infants. We prospectively enrolled a geographically-based cohort of very preterm infants without severe brain injury and born before 32 weeks gestational age. Structural brain MRI was obtained at term-equivalent age and DWMA volume was objectively quantified using a published validated algorithm. These results were compared with visually classified DWMA. We used multivariable linear regression to assess the value of DWMA volume, independent of known predictors, to predict motor development as assessed using the Bayley Scales of Infant & Toddler Development, Third Edition at 3 years of age. The mean (SD) gestational age of the cohort was 28.3 (2.4) weeks. In multivariable analyses, controlling for gestational age, sex, and abnormality on structural MRI, DWMA volume was an independent prognostic biomarker of Bayley Motor scores (beta = −12.59 [95% CI −18.70, −6.48] R2 = 0.41). Conversely, visually classified DWMA was not predictive of motor development. In conclusion, objectively quantified DWMA is an independent prognostic biomarker of long-term motor development in very preterm infants and warrants further study.

Objectively Diagnosed Diffuse White Matter Abnormality at Term Is an Independent Predictor of Cognitive and Language Outcomes in Infants Born Very Preterm

To externally validate the independent value of objectively diagnosed diffuse white matter abnormality (DWMA; also known as diffuse excessive high signal intensity) volume to predict neurodevelopmental outcomes in very preterm infants (≤31weeks of gestational age). A prospective, multicenter, regional population-based cohort study in 98 very preterm infants without severe brain injury on magnetic resonance imaging (MRI). DWMA volume was diagnosed objectively on structural MRI at term-equivalent age using our published algorithm. Multivariable linear regression was used to assess the value of DWMA volume to predict cognitive and language scores on the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 2years corrected age. Of the infants who returned for follow-up (n=74), the mean (SD) gestational age was 28.2 (2.4) weeks, and 42 (56.8%) were boys. In bivariable analyses, DWMA volume was a significant predictor of Bayley-III cognitive and language scores. In multivariable analyses, controlling for known predictors of Bayley-III scores (ie, socioeconomic status, gestational age, sex, and global brain abnormality score), DWMA volume remained a significant predictor of cognitive (P<.001) and language (P=.04) scores at 2years. When dichotomized, objectively diagnosed severe DWMA was a significant predictor of cognitive and language impairments, whereas visual qualitative diagnosis of DWMA was a poor predictor. In this multicenter, prospective cohort study, we externally validated our previous findings that objectively diagnosed DWMA is an independent predictor of cognitive and language development in very preterm infants. We also demonstrated again that visually-diagnosed DWMA is not predictive of neurodevelopmental outcomes.

Fulminant encephalopathy in a child with hyperferritinemic sepsis: a case report

BackgroundSepsis-associated encephalopathy (SAE) is epidemic in intensive care units and recognized as a fatal complication of sepsis. SAE is characterized by diffuse brain dysfunction and the correct diagnosis of SAE requires ruling out direct central nervous system (CNS) infection or other types of encephalopathy, such as hepatic encephalopathy, pulmonary encephalopathy, and other encephalopathy.Case presentationWe reported a rare case of a 5-year-old girl who presented with abdominal pain, vomiting, recurrent seizures, and coma. Brain magnetic resonance imaging (MRI) showed diffuse white matter abnormalities in the brain on day 1. Cerebrospinal fluid (CSF) tests revealed that protein levels and glucose levels were normal without pleocytosis. CSF PCRs for pathogens were all negative. The electroencephalography examination demonstrated diffuse, generalized and slow background activity. The patient showed the symptom of hyperferritinemic sepsis with multiple organ dysfunction syndrome (MODS). SAE was also diagnosed by ruling out other encephalitis or encephalopathy. The patient made marked improvements of clinical symptoms and the lesions on brain imaging disappeared completely within two months after appropriate treatment including antibiotic treatments, methylprednisolone, intravenous immunoglobulin, membrane-based therapeutic plasma exchange (TPE), and continuous renal replacement therapy (CRRT).ConclusionsSAE can be a fatal complication of sepsis which asks for immediate diagnosis and treatment. Few reports have focus on MRI imaging findings on the early onset of hyperferritinemic sepsis with MODS since these children were too ill to undergo an MRI scan. However, SAE might appear before other systemic features of sepsis are obvious, and MRI could show abnormal lesion in the brain during the early course. Therefore, MRI should be performed early to diagnose this fatal complication which would play important roles in improving the clinical outcomes by early initiation with appropriate treatments.

Antecedents of Objectively Diagnosed Diffuse White Matter Abnormality in Very Preterm Infants

BackgroundDiffuse white matter abnormality (diffuse excessive high signal intensity) is the most common finding on structural brain magnetic resonance imaging (MRI) at term-equivalent age in very preterm infants. Yet, there remains a large gap in our understanding of the etiology of diffuse white matter abnormality. Our objective was to evaluate perinatal and neonatal inflammation-associated antecedents of diffuse white matter abnormality on MRI. MethodsWe prospectively enrolled 110 very preterm infants born at ≤31 weeks gestational age and collected data on multiple perinatal/neonatal exposures, especially inflammation initiating-illnesses. We performed structural MRI at term-equivalent age and quantified the volume of diffuse white matter abnormality objectively. Multivariable regression was used to identify clinical antecedents of diffuse white matter abnormality. ResultsThe mean (S.D.) birth gestational age of the final study sample of 98 very preterm infants was 28.3 (2.5) weeks. Multiple inflammation initiating-illnesses were associated with diffuse white matter abnormality in univariate analyses. In multivariable linear regression analyses controlling for gestational age, severe retinopathy of prematurity (P < 0.001) and bronchopulmonary dysplasia (P = 0.006) were independent risk factors, whereas maternal treatment with 17-hydroxyprogesterone (P < 0.001) was protective of later development of objectively quantified diffuse white matter abnormality. ConclusionsWe identified several perinatal and neonatal antecedent clinical factors associated with diffuse white matter abnormality. Although we found some support for inflammation as a common underlying mechanism, larger studies are needed to validate inflammation as a potential common pathway to the development of diffuse white matter abnormality in very preterm infants.

Rotating frame MRI relaxations as markers of diffuse white matter abnormalities in multiple sclerosis

Even though MRI visualization of white matter lesions is pivotal for the diagnosis and management of multiple sclerosis (MS), the issue of detecting diffuse brain tissue damage beyond the apparent T2-hyperintense lesions continues to spark considerable interest. Motivated by the notion that rotating frame MRI methods are sensitive to slow motional regimes critical for tissue characterization, here we utilized novel imaging protocols of rotating frame MRI on a clinical 3 Tesla platform, including adiabatic longitudinal, T1ρ, and transverse, T2ρ, relaxation methods, and Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank 4 (RAFF4), in 10 relapsing-remitting multiple sclerosis patients and 10 sex- and age-matched healthy controls. T1ρ, T2ρ and RAFF4 relaxograms extracted from the whole white matter exhibited a significant shift towards longer relaxation time constants in MS patients as compared to controls. T1ρ and RAFF4 detected alterations even when considering only regions of normally appearing white matter (NAWM), while other MRI metrics such as T1w/T2w ratio and diffusion tensor imaging measures failed to find group differences. In addition, RAFF4, T2ρ and, to a lesser extent, T1ρ showed differences in subcortical grey matter structures, mainly hippocampus, whereas no functional changes in this region were detected in resting-state functional MRI metrics. We conclude that rotating frame MRI techniques are exceptionally sensitive methods for the detection of subtle abnormalities not only in NAWM, but also in deep grey matter in MS, where they surpass even highly sensitive measures of functional changes, which are often suggested to precede detectable structural alterations. Such abnormalities are consistent with a wide spectrum of different, but interconnected pathological features of MS, including the loss of neuronal cells and their axons, decreased levels of myelin even in NAWM, and altered iron content.

Clinical and Imaging Findings of Neonatal Seizures Presenting as Diffuse Cerebral White Matter Abnormality on Diffusion-Weighted Imaging without any Structural or Metabolic Etiology.

PurposeSome patients with neonatal seizures show diffuse, symmetric diffusion-restricted lesions in the cerebral white matter. The aim of this study was to describe clinical and imaging findings of patients with neonatal seizures who had diffuse, symmetric diffusion-restricted lesions without any structural or metabolic etiology.Materials and MethodsA total of 56 neonates aged less than 1 week underwent brain magnetic resonance imaging (MRI) for evaluation of seizures from November 2008 to February 2017. After excluding 43 patients, 13 patients showed diffuse white matter abnormality on diffusion-weighted imaging. Initial and follow-up clinical and MRI findings were analyzed retrospectively.ResultsAll 13 patients were born at full term. Among the ten patients who underwent a stool test for viruses, six were positive for rotavirus and one for astrovirus. MRI revealed diffuse, symmetric diffusion-restricted lesions distributed along the cerebral white matter, thalami, and midbrain variably.ConclusionDiffuse, symmetric diffusion-restricted lesions involving the cerebral white matter can be seen in patients with neonatal seizures without any structural or metabolic etiology. Rotavirus is commonly but not exclusively detected in these patients. Nevertheless, viral infection-associated encephalopathy should be considered for patients with characteristic clinical and MRI findings.

Altered Resting State Functional Activity and Microstructure of the White Matter in Migraine With Aura.

Introduction: Brain structure and function were reported to be altered in migraine. Importantly our earlier results showed that white matter diffusion abnormalities and resting state functional activity were affected differently in the two subtypes of the disease, migraine with and without aura. Resting fluctuation of the BOLD signal in the white matter was reported recently. The question arising whether the white matter activity, that is strongly coupled with gray matter activity is also perturbed differentially in the two subtypes of the disease and if so, is it related to the microstructural alterations of the white matter.Methods: Resting state fMRI, 60 directional DTI images and high-resolution T1 images were obtained from 51 migraine patients and 32 healthy volunteers. The images were pre-processed and the white matter was extracted. Independent component analysis was performed to obtain white matter functional networks. The differential expression of the white matter functional networks in the two subtypes of the disease was investigated with dual-regression approach. The Fourier spectrum of the resting fMRI fluctuations were compared between groups. Voxel-wise correlation was calculated between the resting state functional activity fluctuations and white matter microstructural measures.Results: Three white matter networks were identified that were expressed differently in migraine with and without aura. Migraineurs with aura showed increased functional connectivity and amplitude of BOLD fluctuation. Fractional anisotropy and radial diffusivity showed strong correlation with the expression of the frontal white matter network in patients with aura.Discussion: Our study is the first to describe changes in white matter resting state functional activity in migraine with aura, showing correlation with the underlying microstructure. Functional and structural differences between disease subtypes suggest at least partially different pathomechanism, which may necessitate handling of these subtypes as separate entities in further studies.