White Matter Signal Abnormalities Research Articles

Characterizing white matter hemodynamic markers of lesion burden and cognitive function using arterial spin labeling MRI

AbstractBackgroundWhite matter lesions (WMLs) have been linked to cognitive decline in Alzheimer’s disease (AD), but physiological mechanisms associated with microvascular dysfunction in white matter remain incompletely understood. The purpose of this study was to investigate associations between arterial spin labeling (ASL) magnetic resonance imaging (MRI) markers of white matter hemodynamics and aging, cognitive function, and WML burden.Method Study design. Participants (n=234) provided written consent for this IRB‐approved cross‐sectional study as part of the Human Connectome Aging Project. Participants underwent a range of health and cognitive assessments, including the Montreal Cognitive Assessment (MoCA), and 3 Tesla MRI. Structural imaging. High‐resolution T1‐weighted images were acquired for co‐registration and were processed with FreeSurfer for calculation of white matter signal abnormalities as a measure of WML burden. Hemodynamic imaging. ASL data were acquired using a labeling duration=1500 ms and five equally spaced post‐labeling delays from 200‐2200 ms with spatial resolution=2.5x2.5x2.5 mm3. ASL images were corrected for distortion and for motion. Cerebral blood flow (CBF) and arterial transit time (ATT) were computed using a cross‐correlation approach and a two‐compartment model. Data analysis. Mean CBF and ATT values were calculated inside white matter masks derived using FreeSurfer for each subject and assessed as a function of age, WML burden, and MoCA score.ResultWe found an inverse association between white matter CBF and age (p<0.001) and a direct association between white matter ATT and age (p<0.001), where increasing age corresponded to lower CBF and longer ATT. After including age as a covariate, we found a trend for an inverse relationship between white matter CBF and WML burden (p=0.064), with lower CBF indicating higher WML burden (Figure 2). Lastly, we also found a trend for an inverse association between white matter ATT and MoCA score (p=0.097), with longer ATT indicating lower MoCA scores (Figure 3).ConclusionPreliminary results indicate that impaired hemodynamic properties (lower white matter CBF and longer white matter ATT) may be associated with elevated WML burden and poorer cognition. Further longitudinal studies are necessary to determine whether white matter hemodynamic may represent a prospective marker of WML burden and associated cognitive impairment.

White Matter Alterations in Spastic Paraplegia Type 5: A Multiparametric Structural MRI Study and Correlations with Biochemical Measurements.

In spastic paraplegia type 5, spinal cord atrophy and white matter signal abnormalities in the brain are the main MR imaging alterations. However, the specific mechanism remains unclear. We explored the microstructural changes occurring in spastic paraplegia type 5 and assessed the relation between MR imaging and clinical data. Seventeen patients with spastic paraplegia type 5 and 17 healthy controls were scanned with DTI and T1 mapping on a 3T MR imaging scanner. Fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, and T1 values were obtained using Tract-Based Spatial Statistics and the Spinal Cord Toolbox. Neurofilament light and myelin basic protein in the CSF were measured. The differences in MR imaging and biochemical data between patients with spastic paraplegia type 5 and healthy controls were compared using the Student t test. A widespread reduction of fractional anisotropy values and an elevation of mean diffusivity, T1, and radial diffusivity values were found in most cervical, T4, and T5 spinal cords; corona radiata; optic radiations; and internal capsules in spastic paraplegia type 5. A variation in axial diffusivity values was shown only in C2, C6, and the corona radiata but not in the gray matter. The levels of neurofilament light and myelin basic protein were higher in those with spastic paraplegia type 5 than in healthy controls (myelin basic protein, 3507 [SD, 2291] versus 127 [SD, 219] pg/mL; neurofilament light, 617 [SD, 207] versus 265 [SD, 187] pg/mL; P < .001). No correlation was found between the clinical data and MR imaging-derived measures. Multiparametric MR imaging and biochemical indicators demonstrated that demyelination (mainly) and axonal loss led to the white matter integrity loss without gray matter injury in spastic paraplegia type 5.

Diagnostic analysis of baseline brain MRI features in infants with congenital cytomegalovirus infection: a simplified scoring system

To characterise the magnetic resonance imaging (MRI) features of infants with congenital cytomegalovirus (CMV) and categorise those into a simplified MRI scoring system. Three neuroradiologists reviewed the examinations of 71 infants retrospectively and scored for the presence of a white matter signal abnormality and structural lesion and each MRI was given a score of 0, 1, 2, or 3 for normal, structural abnormality alone, white matter abnormality alone, white matter abnormality plus structural lesion, respectively. Imaging features were outlines according to symptomatology. Chi-square and Spearman's rho were used to test relationships between MRI features and viral loads and MRI score/symptomatic disease respectively. Cohen's Kappa coefficient was used to assess interobserver agreement. Of the 49 abnormal studies, 40% (n=20) were seen in asymptomatic infants. The commonest finding was white matter signal abnormality, followed by cyst formation and polymicrogyria (86%, n=42; 71%, n=35; and 33%, n=16, respectively). Cysts were significantly positively correlated with white matter abnormalities and polymicrogyria. On the MRI score, 31%, 10%, 15%, and 44% obtained a score of 0, 1, 2, and 3, respectively; the MRI score was positively correlated with log-transformed viral loads. Interobserver agreement for the presence of white matter signal abnormality, cyst formation, malformations of cortical development (MCD), and global MRI score was excellent (k=0.82, 0.94, 0.96, and 0.86, respectively). Baseline MRI provides information valuable for treatment decisions, especially in "asymptomatic" infants. The simplified scoring system is easier to use, incorporating solely the imaging findings that are anticipated to have an effect on clinical outcome.

Pons Calcifications and Striatal Necrosis in ADAR1 Aicardi-Goutières Syndrome.

Aicardi-Goutières is an inherited encephalopathy characterized by acquired microcephaly, basal-ganglia calcification, leukodystrophy, cerebral atrophy, and CSF with chronic lymphocytosis and raised interferon-alpha.1 The neuroimage is usually diagnostic, showing basal ganglia and subcortical calcifications on CT and abnormal white matter signal on MRI. The lesions tend to be stable and no treatment is available. A 19-year-old male presented a neurologic condition with pyramidal and extrapyramidal signs associated with cardiomyopathy, livedo, and chilblains that appeared after acute episodes of encephalopathy (age of 2 and 10) precipitated by meningitis vaccine and salmonellosis, followed by neurologic regression and posterior recovering. CT scan (Fig. 1) identified brainstem calcifications (almost confined to the pons), without evident basal ganglia, internal capsule, white matter or dentate nucleus calcifications (faint calcifications could be seen on right putamen). Brain MRI (Fig. 2) showed T2 and T2 FLAIR bilateral hyperintensity on the putamina with atrophy (striatal necrosis), with no white matter signal intensity alterations. The genetic study—WES based gene panel designed for Aicardi-Goutières (including the analysis of MYORG gene)—identified two heterozygous, likely pathogenic, variants in ADAR1 (NM_001111.4:c.577C > G and c.3116A > G). Compound heterozygosity was confirmed by testing both parents, establishing the diagnosis of ADAR1-related Aicardi-Goutières syndrome (Fig. 3). The absence of white matter involvement is described in ADAR1 mutations and further help us to suggest the diagnosis based on image.1, 2 (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. C.P.: 1A, 1C, 2A A.F.B.: 3B J.F.: 3B M.M.: 1B, 3B The authors confirm that the approval of an institutional review board was not required for this work. The informed consent was waived. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. No funding was used for this work. The authors declare no conflict of interest. No financial disclosures for the previous 12 months to declare.

Cerebrovascular Disease and Depressive Symptomatology in Individuals With Subjective Cognitive Decline: A Community-Based Study.

Subjective cognitive decline (SCD) may be the first sign of Alzheimer's disease (AD), but it can also reflect other pathologies such as cerebrovascular disease or conditions like depressive symptomatology. The role of depressive symptomatology in SCD is controversial. We investigated the association between depressive symptomatology, cerebrovascular disease, and SCD. We recruited 225 cognitively unimpaired individuals from a prospective community-based study [mean age (SD) = 54.64 (10.18); age range 35–77 years; 55% women; 123 individuals with one or more subjective cognitive complaints, 102 individuals with zero complaints]. SCD was assessed with a scale of 9 memory and non-memory subjective complaints. Depressive symptomatology was assessed with established questionnaires. Cerebrovascular disease was assessed with magnetic resonance imaging markers of white matter signal abnormalities (WMSA) and mean diffusivity (MD). We combined correlation, multiple regression, and mediation analyses to investigate the association between depressive symptomatology, cerebrovascular disease, and SCD. We found that SCD was associated with more cerebrovascular disease, older age, and increased depressive symptomatology. In turn, depressive symptomatology was not associated with cerebrovascular disease. Variability in MD was mediated by WMSA burden, presumably reflecting cerebrovascular disease. We conclude that, in our community-based cohort, depressive symptomatology is associated with SCD but not with cerebrovascular disease. In addition, depressive symptomatology did not influence the association between cerebrovascular disease and SCD. We suggest that therapeutic interventions for depressive symptomatology could alleviate the psychological burden of negative emotions in people with SCD, and intervening on vascular risk factors to reduce cerebrovascular disease should be tested as an opportunity to minimize neurodegeneration in SCD individuals from the community.

A Case of Influenza Virus-Induced Acute Cerebellitis Treated with Steroid Pulse Therapy

AbstractAcute cerebellitis (AC) is characterized by acute onset cerebellar ataxia brain magnetic resonance imaging (MRI) abnormalities of the cerebellum. The most common cause of AC is viral infection, and some patients with AC experience neurological sequelae. AC associated with influenza virus is extremely rare, and its prognosis and treatment are unknown. We present the case of a 2-year-old boy with influenza virus-induced AC who was treated with pulse steroid therapy. The patient presented with fever, anorexia, vomiting, malaise, altered consciousness, truncal ataxia, dysmetria, and dysarthria. He was diagnosed with influenza using a nasopharyngeal antigen test. Brain MRI showed hyperintense T2 and diffusion-weighted signal abnormalities in the cerebellar white matter and dentate nuclei bilaterally. The patient was treated with two courses of pulse methylprednisolone therapy and recovered completely in 2 months after the onset. The prognosis of AC is poorer than that of acute cerebellar ataxia, which shows similar symptoms to AC with normal brain MRI. The type of virus might also be associated with the prognosis of AC. Literature review showed that one of the five cases (including the present case, 20%) reported with influenza-associated AC was noted to have neurological sequelae, which might be more severe than those of varicella-zoster-related AC. Given that the pathogenesis of AC is assumed to be immune-mediated, pulse methylprednisolone therapy might be a good option for the treatment of influenza virus-induced AC.

Cognitive, Brain and Intracranial Artery Involvement in Beta Thalassemia

Background: Brain involvement in beta thalassemia is scarcely known so far, and available data show different degrees of abnormalities in terms of neuroradiologic findings and cognitive impairment, mainly showing asymptomatic white matter lesions in transfusion dependent thalassemia (TDT; Karimi et al, Ann Hematol 2016) or in non transfusion dependent thalassemia (NTDT; Karimi et al, Ann Hematol 2012 ; Pazgal et al, Thrombosis Research 2016), arterial stenosis in NTDT (Musallam et al, EJH 2011) and a general impairment in cognitive function in TDT (Elalfy et al, Hematology 2017). To our knowledge there are no studies investigating neuroimaging and cognitive function in both groups of patients, comparing results to healthy subjects.Methods: In our observational study thalassemic patients from 4 major Centers in the South of Italy, aged more than 16 years, both Transfusion Dependent (TDT) and Not Transfusion Dependent (NTDT), and healthy volunteers underwent 3T brain MRI including a FLAIR sequence and intracranial time-of-flight MR-angiography. Three neuroradiologists blinded of clinical data evaluated the MR-exams reporting the presence of artery stenosis and aneuryms and the presence of white matter signal abnormalities graded according to the Fazekas score; the number and the size of parenchymal lesions (<0.5cm, 0.5-1.5cm, >1.5cm) were recorded. Both patients and controls were administered the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) to detect cognitive ability, and results were analyzed by a team of blinded psychologists and psychiatrists. Clinical and laboratory data were collected to correlate neurologic and psychometric findings with disease history and severity.Results: Seventy-four thalassemic patients (46/74 females, mean-age 35.2±11.4 years, range 16-66; 51 TDT and 23 NTDT; mean hemoglobin 9.3±1.4 g/dl, range 7.5-12; 41 splenectomized; 34 on prophylactic aspirin) and 56 healthy controls (36/56 females, mean-age 34.2±11.7 years, range 17-66) were enrolled. No intracranial artery stenosis was detected. Patients and controls did not differ regarding the incidence rate of aneurysms (9.46% vs 9.67%). White matter lesions (WML) were found both in patients and controls, but the prevalence (35/74; 47.30% vs 28/56; 50.0%), the number (4.1 vs 4.6), the size and the Fazekas score did not differ between the groups. Compared to controls, patients presenting WML tend to be younger (35.32y compared to 39.89y, p= 0.033). No differences in WML were found between TDT and NTDT, nor between patients on aspirin and others, and splenectomy was associated with an increased lesion burden only in TDT (mean 5.56 versus 1.53, p= 0.048); in splenectomized patients on aspirin the number and prevalence of WML was lower compared to those splenectomized not on prophylaxis, but the difference did not reach the statistical significance. Patients with WML did not differ from others in terms of comorbidities, hemoglobin, platelets, erythroblasts, ferritin, hemolysis markers and chelation therapies. The presence of WML did not correlate with cognitive impairment as measured by the Intelligence Quotient (IQ) derived from the WAIS-IV test, both in patients and in controls. IQ in patients was significantly lower than controls, and this finding remained significant after correction for education (IQ: 82.75±11.11 in patients, 93.96±SD13.22 in controls, p=0.032), regardless of the presence of WML, that was again comparable.Conclusions: Beta-thalassemia and chronic blood transfusion treatment do not seem to imply significant brain and intracranial artery changes, although cognitive function seems to be affected. Further analysis are required to clarify if the general cognitive impairment derives from functional changes in cerebral connectivity, or if it is one of the effect of the chronic course of the disease. DisclosuresNo relevant conflicts of interest to declare.

Short-term developmental outcomes in neonates born to mothers with COVID-19 from Wuhan, China.

BackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease. The consequences of SARS-CoV-2 exposure in infants remain unknown. Therefore, this study aims to investigate whether neonates born to mothers with COVID-19 have adverse brain development.MethodsThis multicenter observational study was conducted at two designated maternal and children’s hospitals in Hubei Province, mainland China from February 1, 2020 to May 15, 2020. Neonates born to mothers with COVID-19 were enrolled. Brain magnetic resonance imaging (MRI) findings, and volumes of grey and white matters, and physical growth parameters were observed at 44 weeks corrected gestational age.ResultsOf 72 neonates born to mothers with COVID-19, 8 (11%) were diagnosed with COVID-19, 8 (11%) were critically ill, and no deaths were reported. Among the eight neonates that underwent brain MRI at corrected gestational age of 44 weeks, five neonates were diagnosed with COVID-19. Among these five neonates, three presented abnormal MRI findings including abnormal signal in white matter and delayed myelination in newborn 2, delayed myelination and brain dysplasia in newborn 3, and abnormal signal in the bilateral periventricular in newborn 5. The other three neonates without COVID-19 presented no significantly changes of brain MRI findings and the volumes of grey matter and white matter compared to those of healthy newborns at the equivalent age (P > 0.05). Physical growth parameters for weight, length, and head circumference at gestational age of 44 weeks were all above the 3rd percentile for all neonates.ConclusionsSome of the neonates born to mothers with COVID-19 had abnormal brain MRI findings but these neonates did not appear to have poor physical growth. These findings may provide the information on the follow-up schedule on the neonates exposed to SARS-CoV-2, but further study is required to evaluate the association between the abnormal MRI findings and the exposure to SARS-CoV-2.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12519-021-00426-z.

Brain Atrophy Subtypes and the ATN Classification Scheme in Alzheimer’s Disease

Introduction: We investigated the association between atrophy subtypes of Alzheimer’s disease (AD), the ATN classification scheme, and key demographic and clinical factors in 2 cohorts with different source characteristics (a highly selective research-oriented cohort, the Alzheimer’s Disease Neuroimaging Initiative [ADNI]; and a naturalistic heterogeneous clinically oriented cohort, Karolinska Imaging Dementia Study [KIDS]). Methods: A total of 382 AD patients were included. Factorial analysis of mixed data was used to investigate associations between AD subtypes based on brain atrophy patterns, ATN profiles based on cerebrospinal fluid biomarkers, and age, sex, Mini Mental State Examination (MMSE), cerebrovascular disease (burden of white matter signal abnormalities, WMSAs), and APOE genotype. Results: Older patients with high WMSA burden, belonging to the typical AD subtype and showing A+T+N+ or A+T+N− profiles clustered together and were mainly from ADNI. Younger patients with low WMSA burden, limbic-predominant or minimal atrophy AD subtypes, and A+T−N− or A+T−N+ profiles clustered together and were mainly from KIDS. APOE ε4 carriers more frequently showed the A+T−N− and A+T+N− profiles. Conclusions: Our findings align with the recent framework for biological subtypes of AD: the combination of risk factors, protective factors, and brain pathologies determines belonging of AD patients to distinct subtypes.

Magnetic resonance imaging findings in children with Parry-Romberg syndrome and en coup de sabre

BackgroundThe aim of this study was to: (i) describe the abnormalities seen on brain imaging in a group of children with en coup de sabre (EDCS) with/without Parry-Romberg syndrome (PRS); and (ii) identify clinical predictors of brain imaging abnormalities.MethodsThis was a single centre (Great Ormond Street Hospital, London) retrospective case series of patients with ECDS/PRS seen from 2000 to 2018. We identified patients with cutaneous manifestations consistent with the clinical descriptions of ECDS/PRS. Presenting clinical, laboratory, and radiological brain findings are described. Results are expressed as medians and ranges or frequencies and percentages. Fisher’s exact test was used to identify clinical associations with magnetic resonance imaging (MRI) abnormalities.ResultsFourteen patients were studied: 6 males and 8 females; median age 14 years (range 3–20). We observed neuroimaging abnormalities in 2/6 ECDS and 5/8 ECDS/PRS patients. White matter signal abnormality, dystrophic calcification, leptomeningeal enhancement, and sulcal crowding were the typical findings on brain imaging. A total of 50% of patients had no MRI abnormality despite some of these patients having neurological symptoms. The presence of seizures was significantly associated with ipsilateral enhanced white matter signalling on MRI (p < 0.05).ConclusionsIn summary, we observed several distinct radiographic patterns associated with ECDS/PRS. Seizure disorder was strongly associated with the presence of ipsilateral enhanced white matter signalling. Improved neuroimaging techniques that combine morphological with functional imaging may improve the detection rate of brain involvement in children with ECDS/PRS in the future.

A hypomyelinating leukodystrophy in German Shepherd dogs

BackgroundShaking puppy syndrome is commonly attributed to abnormal myelination of the central nervous system.Hypothesis/ObjectivesTo report the long‐term clinical course and the imaging characteristics of hypomyelinating leukodystrophy in German Shepherd dogs.Animals and MethodsThree related litters with 11 affected dogs.ResultsThe 11 affected dogs experienced coarse, side‐to‐side tremors of the head and trunk, which interfered with normal goal‐oriented movements and disappeared at rest. Signs were noticed shortly after birth. Nine dogs were euthanized, 3 dogs underwent pathological examination, and 2 littermates were raised by their breeder. Tremors improved gradually until 6 to 7 months of age. Adult dogs walked with severe residual pelvic limb ataxia. One dog developed epilepsy with tonic‐clonic seizures at 15 months of age. Conventional magnetic resonance imaging (MRI) disclosed homogenous hyperintense signal of the entire subcortical white matter in 3 affected 7‐week‐old dogs and a hypointense signal in a presumably unaffected littermate. Subcortical white matter appeared isointense to gray matter at 15 and 27 weeks of age on repeated MRI. Abnormal white matter signal with failure to display normal gray‐white matter contrast persisted into adulthood. Cerebellar arbor vitae was not visible at any time point. Clinical signs, MRI findings, and pathological examinations were indicative of a hypomyelinating leukodystrophy. All parents of the affected litters shared a common ancestor and relatedness of the puppies suggested an autosomal recessive mode of inheritance.ConclusionWe describe a novel hypomyelinating leukodystrophy in German Shepherd dogs with a suspected inherited origin.

FUNCTIONAL NEUROMARKERS IN PARKINSON’S DISEASE (PD)

New neurotechnologies which help to study not only the structure but also brain work, especially in milliseconds, allow for a more accurate diagnosis of a given disease entity. The aim of our study was to characterize the functional neuromarkers, including a new neuromarker, that is high rolandic beta, in Parkinson’s disease (PD). A 76-year-old male patient, a university professor, a widower, in an intimate relationship with a beloved partner, was tested in the Reintegration and Training Center of the Polish Society of Neuropsychology. Five years earlier (when he was 71 years old), following long-term stress, he had had a transient ischemic attack (TIA). In the following years he experienced two neurological episodes, and was diagnosed, on the basis of MRI findings and clinical symptoms, with vascular (multi-infarct) Parkinsonism. A sudden deterioration in his functioning, including hand tremors at rest, bradykinesia (motor slowdown), asymmetrical gait difficulties, postural instability, and falls typical for PD, as well as MRI finding (the appearance of ‘a swallow tail ’ on the left side, and the lack on the right of the substantia nigra within the midbrain) was the cause of further differential diagnosis. He was assessed using the HBI methodology (Kropotov 2016; Pąchalska, Kaczmarek, Kropotov 2014). EEG was recorded from 19 scalp sites, in resting state conditions, with eyes open and eyes closed, and during the cued GO/NOGO tasks with animal/plants as GO/NOGO stimuli. The electrodes were applied according to the International 10-20 system. The EEG was recorded referentially to linked ears, allowing for a computational re-referencing of the data (remontaging). Event related potentials (ERPs) were used to assess the functional changes manifested by the patient. To compare our patient with healthy controls we used the normative Human Brain Index (HBI), a database obtained through joint research by Swiss, Norwegian, Polish and Russian neuroscientists (Kropotov 2018). This database included behavioral parameters and ERP measures in 6 different neuropsychological tasks for 1000 healthy subjects. What is striking, no signs of cognitive dysfunction was found; however observed were an asymmetrical frontal lobe alpha (a neuromarker of depression) and excessive Rolandic beta (a neuromarker of Parkinson’s disease). We will discuss the results on the basis of recent subject literature findings, including the personal factors that might influenced the process of the diagnosis and treatment of this patient, ones which should be also taken into account in any differential diagnosis. The obtained results show the importance of using HBI methodology in clinical practice. Physicians involved in the diagnosis and treatment of those with progressive ambulatory impairment and an abnormal white matter (WM) signal on neuroimaging, should when formulating any differential diagnosis consider the use of this approach. ------------------------------------------------------------------------------------------------------------------------------------

Polyglucosan body myopathy 1 may cause cognitive impairment: a case report from China

BackgroundPolyglucosan body myopathy 1 (PGBM1) is a type of glycogen storage disease that can cause skeletal muscle myopathy and cardiomyopathy with or without immunodeficiency due to a pathogenic mutation in the RBCK1 gene. PGBM1 has been reported in only 14 European and American families, and no cognitive impairment phenotype was reported. Its prevalence in Asia is unknown.Case presentation:We report a Chinese boy with teenage onset of skeletal muscle myopathy and mild cognitive impairment. Whole-exome sequencing analysis identified a homozygous missense mutation in RBCK1 (c.1411G > A:p.Glu471Lys). A muscle biopsy indicated the accumulation of periodic acid-Schiff-positive material, which could be ubiquitinated by immunohistochemistry with an anti-ubiquitin antibody. In skeletal muscle tissue, HOIL-1 and HOIP protein levels were lower than those in the control, confirming the phenotype of an RBCK1 mutation. MRI revealed abnormal cerebral white matter signals. Immune system and cardiac examination found no abnormalities. The patient was diagnosed with PGBM1 with no effective treatment.ConclusionsThis case from China with a novel homozygous missense mutation in RBCK1 extends the phenotypic spectrum and geographical distribution of PGBM 1, which may cause cerebral white matter changes and cognitive impairment.

Heterogeneity of Cerebral White Matter Lesions and Clinical Correlates in Older Adults

Cerebral white matter signal abnormalities (WMSAs) are a significant radiological marker associated with brain and vascular aging. However, understanding their clinical impact is limited because of their pathobiological heterogeneity. We determined whether use of robust reliable automated procedures can distinguish WMSA classes with different clinical consequences. Data from generally healthy participants aged >50 years with moderate or greater WMSA were selected from the Human Connectome Project-Aging (n=130). WMSAs were segmented on T1 imaging. Features extracted from WMSA included total and regional volume, number of discontinuous clusters, size of noncontiguous lesion, contrast of lesion intensity relative to surrounding normal appearing tissue using a fully automated procedure. Hierarchical clustering was used to classify individuals into distinct classes of WMSA. Radiological and clinical variability was evaluated across the individual WMSA classes. Class I was characterized by multiple, small, lower-contrast lesions predominantly in the deep WM; class II by large, confluent lesions in the periventricular WM; and class III by higher-contrast lesions restricted to the juxtaventricular WM. Class II was associated with lower myelin content than the other 2 classes. Class II was more prevalent in older subjects and was associated with a higher prevalence of hypertension and lower physical activity levels. Poor sleep quality was associated with a greater risk of class I. We classified heterogeneous subsets of cerebral white matter lesions into distinct classes that have different clinical risk factors. This new method for identifying classes of WMSA will be important in understanding the underlying pathophysiology and in determining the impact on clinical outcomes.

Role of Double Inversion Recovery Sequence in Neuro-imaging on 3 Tesla MRI

Double Inversion Recovery (DIR) is a robust sequence designed to suppress fat and water signals using two 180° inversion pulses to produce prominent gray matter contrast with high spatial resolution. It has proven to be more sensitive in delineating white matter signal abnormalities than conventional MR techniques. In our study, the highest image contrast with lesion load was observed using DIR over FLAIR and T2 weighted imaging. DIR is evidently valuable for the detection of demyelinating lesions observed in multiple sclerosis (MS), malignancies, epileptogenic foci, and cortical anomalies. Hence this pictorial review is intended to assess the diagnostic efficacy of DIR modality in clinical Neuro-imaging.

Quantitative analysis of double inversion recovery and FLAIR signals in temporal lobe epilepsy

This study aimed to quantitatively compare the signals from double inversion recovery (DIR) and fluid‐attenuated inversion recovery (FLAIR) in temporal lobe epilepsy (TLE) with a focus on anterior temporal lobe white matter abnormal signal (ATLAS) lesions. We recruited 59 patients with TLE (32 left, 27 right) and 24 healthy controls (HCs). All patients underwent 3T-MRI scans including 3D DIR and FLAIR images, and the images were normalized and compared among the three groups by the software program SPM 12. We also explored the association of the ATLAS with disease duration, seizure types, and the existence of hippocampal sclerosis (HS). As a result, compared to the HCs, there were significantly increased DIR signals in the ipsilateral anterior temporal white matter of both the left and right TLE patients. There was no significant signal difference in FLAIR images between the HCs and patients except for a trend-level increase in left TLE. There was also no significant association between the ATLAS and disease duration, seizure type, or HS. These results quantitatively confirmed the significant signal increases of DIR in the ipsilateral anterior temporal lobe in both left and right TLE, whereas FLAIR revealed no significant between-group differences. These findings may indicate greater usefulness of DIR compared to FLAIR for detecting ATLAS lesions.

MRI measures of neurodegeneration in the LEADS cohort

AbstractBackgroundAlthough early‐onset AD (EOAD) and late‐onset AD (LOAD) share the same pathologic substrate, there are notable differences in their atrophy patterns compared with LOAD. EOAD is associated with greater baseline cortical atrophy, less medial temporal lobe involvement and often more severe AD pathology than LOAD. In addition, MRI measures can be informative about likely etiology in patients with a clinical phenotype suggestive of EOAD who turn out to have biomarkers not consistent with EOAD.MethodIn LEADS, the goals of the MRI core are to 1) collect and perform quality control procedures using the ADNI 3 protocol; 2) collect and analyze T1‐ and T2‐weighted MRI data to obtain measures of atrophy (neurodegeneration) and white matter signal abnormalities; 3) collect and analyze advanced diffusion, perfusion, resting‐state functional MRI, and high‐resolution medial temporal lobe sequences. At present, we are focusing on the Freesurfer‐based analysis of T1‐weighted MRI data for the purposes of evaluating atrophy patterns to compare patients with elevated amyloid vs. those with low amyloid, and furthermore to try to identify patterns suggestive of non‐AD pathologies. Furthermore, we are comparing several methods for defining neurodegeneration from T1‐weighted MRI scans, including whole brain volume, hippocampal volume, average cortical thickness, and AD‐signature cortical thickness.ResultAs a group, the T1‐derived atrophy pattern relative to controls from patients with elevated amyloid show prominent lateral temporoparietal and posterior cingulate/precuneus atrophy. The low‐amyloid group do not show a clear pattern of atrophy, as a group. AD‐signature cortical thickness differs between EOAD and controls but not between EO‐nonAD and controls, while hippocampal volume differs between both patient groups and controls. In some patients with low amyloid, atrophy patterns are suggestive of likely FTLD pathology.ConclusionThe initial MRI data from LEADS support the observations reported from smaller studies of EOAD. Analyses are ongoing to determine whether MRI‐based definitions of neurodegeneration previously developed in LOAD are generalizable to EOAD.

Atypical neuroimaging characteristics of hemophagocytic lymphohistiocytosis in infants: a case series of hemorrhagic brain lesions in the deep grey matter

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem condition associated with uncontrolled overproduction and infiltration of lymphocytes and histiocytes predominantly in liver, lymph nodes, spleen, and central nervous system. Neuroimaging findings on MRI are fairly nonspecific and classically include periventricular white matter signal abnormalities and diffuse atrophy. Focal parenchymal lesions may demonstrate post contrast ring or nodular enhancement and calcification. However, the MR imaging characteristics can be highly variable. Here, we present two cases of HLH in infants with multiple hemorrhagic lesions mostly depicted in both thalami and basal ganglia regions. Thalamic, basal ganglia, and brain stem involvement with hemorrhagic changes in HLH are rarely described in literature. Early diagnosis of HLH may be lifesaving. Awareness of the disease is necessary to investigate its characteristic findings and avoiding a delay in diagnosis.

Brain Magnetic Resonance Findings in 117 Children with Autism Spectrum Disorder under 5 Years Old.

We examined the potential benefits of neuroimaging measurements across the first 5 years of life in detecting early comorbid or etiological signs of autism spectrum disorder (ASD). In particular, we analyzed the prevalence of neuroradiologic findings in routine magnetic resonance imaging (MRI) scans of a group of 117 ASD children younger than 5 years old. These data were compared to those reported in typically developing (TD) children. MRI findings in children with ASD were analyzed in relation to their cognitive level, severity of autistic symptoms, and the presence of electroencephalogram (EEG) abnormalities. The MRI was rated abnormal in 55% of children with ASD with a significant prevalence in the high-functioning subgroup compared to TD children. We report significant incidental findings of mega cisterna magna, ventricular anomalies and abnormal white matter signal intensity in ASD without significant associations between these MRI findings and EEG features. Based on these results we discuss the role that brain MRI may play in the diagnostic procedure of ASD.

Inherited paediatric neurometabolic disorders, can brain magnetic resonance imaging predict?

Objectives:To evaluate diagnostic capability of brain magnetic resonance imaging (MRI) in detection of inherited neurometabolic disorders.Methods:This retrospective observational study was performed in Radiology Department at our Hospital in Dhahran, from January 2013 to January 2020. We evaluated brain MRIs of children (under 5) who were referred to pediatric neurology for clinical suspicion of neuro-developmental delay and metabolic disease. Known perinatal ischemia and birth trauma cases were excluded. Imaging criteria included: (i) bilateral symmetric white matter signal abnormality, (ii) diffusion restriction affecting bilateral deep grey nuclei with or without brainstem involvement, (iii) brain atrophy or edema with abnormal white matter signal, (iv) characteristic MR spectroscopic finding. Presence of any one of these findings was considered positive for neurometabolic disease. Two neuroradiologists interpreted MRIs with substantial interobserver agreement. Diagnoses were confirmed on biochemical/ metabolic screening and genetic testing. A 2 × 2 contingency table was used for results. Chi square test was used to determine association.Results:Out of 133 cases, 72 (49 males, 90% AR) were found to have neurometabolic disorders. Sensitivity, specificity, positive and negative predictive values were calculated as 81.94% (CI, 71.11-90.02), 67.21% (CI, 54.00-78.69), 74.68% (CI, 66.96-81.11) and 75.93% (CI, 65.16-84.17) respectively. Findings were found significant (p-value=0.0001).Conclusion:Brain MRI can help to predict inherited neurometabolic disorders considering certain findings.