MRI White Matter Lesions Research Articles

Venous Collagenosis as Pathogenesis of White Matter Hyperintensity.

Periventricular white matter hyperintensities (pvWMHs) are commonly observed on MRI in older individuals and are associated with cognitive and motor decline. The etiology of pvWMH remains unknown. Venous collagenosis has been implicated, which may also interfere with perivascular fluid flow leading to dilation of perivascular spaces (PVS). Here, we examine relationships between in vivo pvWMH volume and ex vivo morphological quantification of collagenosis and the PVS in veins and arteries. Brain tissue from 25 Oregon Alzheimer's Disease Research Center subjects was selected to cover the full range of WMH burden. Tissue from white matter abutting the ventricle was stained with Masson's trichrome and smooth muscle actin. An automated hue based algorithm identified and segmented vessel into collagenized vessel walls, lumen, and PVS. Multiple linear regressions with pvWMH volume as the dependent variable and either collagen thickness or PVS width were performed with covariates of vessel diameter, age at death, sex, and interval between MRI and death. PVS width and collagen thickness were significantly correlated in both arteries (r=0.21, p=0.001) and veins (r=0.23, p=0.001). Increased venous collagen (p=0.017) was a significant predictor of higher pvWMH burden while arterial collagen was not (p=0.128). Neither PVS width in arteries (p=0.937) nor veins (p=0.133) predicted pvWMH burden. These findings are consistent with a model in which venous collagenosis mediates the relationship between vascular risk factors and pvWMH. This study confirms the importance of changes to the venous system in contributing to MRI white matter lesions commonly observed with advanced age. ANN NEUROL 2022;92:992-1000.

Detection of subtle white matter lesions in MRI through texture feature extraction and boundary delineation using an embedded clustering strategy

White matter lesions (WML) underlie multiple brain disorders, and automatic WML segmentation is crucial to evaluate the natural disease course and effectiveness of clinical interventions, including drug discovery. Although recent research has achieved tremendous progress in WML segmentation, accurate detection of subtle WML present early in the disease course remains particularly challenging. Here we propose an approach to automatic WML segmentation of mild WML loads using an intensity standardisation technique, gray level co-occurrence matrix (GLCM) embedded clustering technique, and random forest (RF) classifier to extract texture features and identify morphology specific to true WML. We precisely define their boundaries through a local outlier factor (LOF) algorithm that identifies edge pixels by local density deviation relative to its neighbors. The automated approach was validated on 32 human subjects, demonstrating strong agreement and correlation (excluding one outlier) with manual delineation by a neuroradiologist through Intra-Class Correlation (ICC = 0.881, 95% CI 0.769, 0.941) and Pearson correlation (r = 0.895, p-value < 0.001), respectively, and outperforming three leading algorithms (Trimmed Mean Outlier Detection, Lesion Prediction Algorithm, and SALEM-LS) in five of the six established key metrics defined in the MICCAI Grand Challenge. By facilitating more accurate segmentation of subtle WML, this approach may enable earlier diagnosis and intervention.

Mapping associations across multiple aspects of Alzheimer disease and the role of CSF biomarkers in individuals without dementia

AbstractBackgroundAlzheimer disease (AD) is a complex disorder involving biological, clinical, and lifestyle aspects. Assessing all these aspects simultaneously allows to better disentangle the position of CSF marker abnormalities across AD stages. Here, we employ a novel statistical method specifically developed to reveal meaningful associations across multiple aspects that can occur simultaneously within individuals.MethodWe selected the baseline data from the European Prevention of Alzheimer Disease cohort of individuals without dementia (www.ep‐ad.org; n=1243, mean±SD age = 65±7 years old, 57% female, 18% CDR ≥0.5) covering ten aspects: demographics including APOE‐genotype, cerebrospinal fluid (CSF) biomarkers, MRI visual rating scales, MRI regional volumes, MRI white matter lesions, cognition, function, psychological factors, general physical health, and comorbidities. We used regularized simultaneous component analysis (regSCA), a statistical technique that extracts relevant components which explain variation within and across these aspects, and robustly selects the appropriate variables [1, 2].ResultThe optimal model revealed eight components explaining 51% of the total variance. Figure 1 presents an overview of all components, showing the strengths and directions of the associations between variables. Five components included CSF biomarkers, which were (1) Abeta42‐dominant, (2) Tau‐dominant, (3) function‐dominant, (4) age‐dominant and, (5) white matter lesion‐dominant. In (3) and (4), Abeta42 and Tau related to cognition and function. Only (3) was independent of age, and may represent purely AD. In (5), Abeta42 related to white matter lesions, and may represent the degree cerebral amyloid angiopathy (CAA). Abeta42 in (1) and Tau in (2) related to APOE‐genotype, suggesting these may be independent effects. The three components unrelated to CSF biomarkers were: (6) sex‐dominant, (7) psychological factors‐dominant, and (8) life‐style‐only.ConclusionAnalysis of robust associations across multiple aspects of AD simultaneously implicated CSF biomarkers in five components. These components may represent risk‐profiles and AD disease processes in cognitively normal and mildly impaired individuals. Our next step is to investigate the stability of the components and their co‐expression within individuals. This overview of complex relationships between AD‐related aspects, helps to understand the disease mechanisms in of AD. This novel approach can be a solution for analyses of large and complex datasets in AD.

The importance of follow-up and re-diagnosis of patients with demyelinating syndrome suspicion - a case study of a conversion from radiologically isolated syndrome to clinically definite multiple sclerosis

Introduction. Radiologically isolated syndrome (RIS) is a term to describe criteria of diagnosis for the individuals, who underwent brain MRI because of other reasons than multiple sclerosis (MS) suspicion, but turned out to have white matter lesions similar to those present in patients with diagnosed MS. RIS is a separate entity with the presence of MR detected lesions strongly suggestive of MS in patients with no neurological manifestations. Although RIS is not the first stage of MS in every individual, 30-45% of them will present clinical symptoms later. There is a consensus, that about 1/3 of RIS patients will convert to clinically definite MS (CDMS) within 5 years of follow-up. There are some significant predictors of conversion, such as: age (&lt; 37 when diagnosed), male sex and presence of lesions in spinal cord.Case report. We describe a case of a 35-year-old female patient who was initially diagnosed with RIS after MRI performed due to migraine. After about year and a half of follow-up she presented first clinical manifestation (temporary left eye blindness) followed by second episode (in the second eye), a progression in MRI and appearance of oligoclonal bands in cerebrospinal fluid.Discussion. Among individuals with incidentally found lesions in MRI, only few happen to have white matter findings similar to demyelinating lesions in patients with CDMS. Non-specific MRI white matter lesions are much more often than than those fulfilling 2017 MAGNIMS criteria.There is more research needed to determine significant risk factors for conversion from RIS to CDMS. In RIS patients watchful neurological supervision is indispensable.

Sporadic Japanese case of adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia caused by a de novo p.Phe849del mutation in CSF1R

AbstractAdult‐onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an autosomal dominant neurodegenerative disorder caused by mutations in the colony‐stimulating factor 1 receptor (CSF1R) gene. We, herein, report the first Japanese case of ALSP caused by a de novo p.Phe849del mutation in CSF1R: a 44‐year‐old man who presented callosal disconnection symptoms. Brain MRI revealed dilation of the lateral ventricles, periventricular white matter hyperintensities, and thinning of the corpus callosum with hyperintensities on T2‐weighted and FLAIR images. Brain single photon emission computed tomography (SPECT) showed hypoperfusion in the anterior corpus callosum. White matter lesions in MRI and hypoperfusion in SPECT increased with age. A brain biopsy at 44 years revealed axonal spheroids. Callosal disconnection symptoms and hypoperfusion in the anterior corpus callosum may be important indicators of ALSP, especially when caused by a p.Phe849del CSF1R mutation.

Different diagnoses of patients referred to multiple sclerosis outpatient clinic

The aim of this study is to investigate the frequency and type of MS mimics in the patients who were diagnosed with MS in other centers and applied to our MS center in the last 3 years. We included all patients who applied to our MS clinic between January 1, 2016 and December 31, 2018 for the first time in our retrospective study. The definitive diagnosis was recorded and demographic, clinical, laboratory, electrophysiological and radiological variables were collected. 296 patients were included in the study. Of 235 patients referred from other centers, 166 (70.6%) confirmed the diagnosis of definitive MS, while 69 (29.4%) had an alternative diagnosis. While 52.5% of the patients referred with clinical suspicion were diagnosed with MS, 8.1% of those who were referred with radiological suspicion were diagnosed with MS. The most frequently diagnosed diagnoses were: non-specific MRI white matter lesions (17.9%), migraine (11.5%), psychogenic (8.9%), systemic autoimmune diseases (6.4%), NMO (4, 7%), and genetic diseases (1,7%). Factors that assisted in the correct diagnosis were; non-specific MRI findings, normal neurological examination, normal evoked potentials, isolated MRI findings, MRI findings not fulfilling 2010 McDonald criteria, absence of oligoclonal bands, cognitive presenting symptoms, family story. Our study shows that 29,4% of patients had an alternative diagnosis. The most common mimickers of MS in our center is not different from what has been described in other countries. Neurological signs and symptoms, age, family story, DNA analysis, laboratory and radiological findings can help with the true diagnosis.

Alternative diagnoses in patients referred to specialized centers for suspected MS

ObjectivesThe aim of this study is to explore the frequency, type, and predictors of alternative diagnoses among patients referred with a recent diagnosis of multiple sclerosis (MS) to two specialized MS centers in the Middle East. MethodsThis is a retrospective review of a prospectively followed cohort of MS patients at 2 University specialized MS centers. All patients referred for MS were included. The final diagnosis was recorded and demographic, clinical, laboratory, electrophysiological and radiological variables were collected. ResultsA total of 554 patients were included in this study of which 431 were referred for diagnostic confirmation. The final diagnosis of MS was confirmed in 300 (70%), while 114 (26%) turned out to have an alternative diagnosis and 15 (3.5%) fulfilled criteria for radiologically isolated syndrome (RIS). The most common alternative diagnoses were psychogenic (16.3%), non-specific MRI white matter lesions (14.7%), NMO (9.5%), migraine (8.6%) and systemic autoimmune disorders (8.6%). The strongest predictors of a final diagnosis of MS were: younger age, presence of oligoclonal bands in the CSF, periventricular, corpus callosum, spinal (P<0.0001), or enhancing lesions (P<0.005) on MRI. ConclusionsOur study shows that 30% of patients referred for a suspicion of MS end up with a different diagnosis. The most common alternative diagnoses of MS in the Middle East are not different from what has been described in Western countries. Age, MRI and CSF findings can help with the differential diagnosis.

Automated Detection of Lupus White Matter Lesions in MRI.

Brain magnetic resonance imaging provides detailed information which can be used to detect and segment white matter lesions (WML). In this work we propose an approach to automatically segment WML in Lupus patients by using T1w and fluid-attenuated inversion recovery (FLAIR) images. Lupus WML appear as small focal abnormal tissue observed as hyperintensities in the FLAIR images. The quantification of these WML is a key factor for the stratification of lupus patients and therefore both lesion detection and segmentation play an important role. In our approach, the T1w image is first used to classify the three main tissues of the brain, white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), while the FLAIR image is then used to detect focal WML as outliers of its GM intensity distribution. A set of post-processing steps based on lesion size, tissue neighborhood, and location are used to refine the lesion candidates. The proposal is evaluated on 20 patients, presenting qualitative, and quantitative results in terms of precision and sensitivity of lesion detection [True Positive Rate (62%) and Positive Prediction Value (80%), respectively] as well as segmentation accuracy [Dice Similarity Coefficient (72%)]. Obtained results illustrate the validity of the approach to automatically detect and segment lupus lesions. Besides, our approach is publicly available as a SPM8/12 toolbox extension with a simple parameter configuration.

P58. Primary hyperparathyroidism mimicking multiple sclerosis? A case report

A 46-year-old Caucasian female patient was admitted to our hospital with suspected relapse of multiple sclerosis (MS). Diagnosis was made 2 years ago by unspecific white matter lesions, oligoclonal bands in the cerebrospinal fluid and a first episode with a slight hemiparesis left, which remitted in a few weeks. A treatment with interferon beta 1a was introduced. Since that there were no relapses noted. Since a few days she suffered fluctuating muscle weakness, dysarthria, fatigue and mood changes. Clinical examination revealed brisk tendon reflexes, no paresis but severe hypalgesia of both arms. After a 20 m walk she was not able to walk fast and she reported a feeling like a lead weight in her legs. A prednisolone pulse was given for 5 days. Brain MRI showed a new small single contrast enhancing lesion parieto-occipital. Patient shows a slight improvement, mainly concerning their fatigue. Few days after completed prednisolone treatment, the fluctuating muscle weakness progressed. She reported cognitive impairment and paroxysmal panic attacks. Repeated MRI (3 Tesla) oft he brain and cervical spine showed no new lesions. Prednisolone pulse was initiated repeatedly. Laboratory investigations revealed slight elevation of serum calcium. Therefore parathyroid hormone level was evaluated and showed 3-fold elevation. Further evaluations by endocrinologists showed a large adenoma oft he right caudal parathyroid gland. Surgery was planned. Retrospectively serum calcium showed elevated values 4 years ago, when patient was first admitted to a neurology department because of cerebral MRI white matter lesions without clinical symptoms. This case raises the question wether primary hyparathyroidism is a MS mimic? A recent study showed an association between plasma parathyroid hormone and white matter lesions (Hagstroem et al., 2014). Non focal muscle weakness is sometimes reported in primary hyperparathyroidism (pHPT), but severe sensory symptoms are not reported to our knowledge. In a series of pHPT patients subclinical changes of sensory nerve conduction velocity has been showed (Diniz ET, 2013). In our patient sensory electroneurography was normal, but hypalgesia was consistent in the quantitative sensory testing (QST). Our report present further neurophysiologic tests and will discuss possible underlying mechanisms oft he clinical symptoms in detail.

THU0201 Cognitive impairment in behçet’s disease is not associated to systemic disease activity, cumulative prednisone dose or white-matter lesions

BackgroundNeuro-Behçet’s disease (NBD) may present cognitive and behavioral symptoms, such as pseudobulbar affect, personality disorders and memory impairment. Because of its predilection for brainstem and basal ganglia, explanations for cognitive/behavioral...

Diffusion tensor imaging and magnetic resonance spectroscopy of transient cerebral white matter lesions in X-linked Charcot-Marie-Tooth disease

BackgroundX-linked Charcot-Marie-Tooth disease (CMTX) is a common inherited axonal or mixed axonal-demyelinating neuropathy. The disease is caused by mutations in the GJB1 gene encoding the gap junction protein connexin32, which is expressed in both Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. Several reports have described CMTX patients presenting with transient and recurrent central nervous system (CNS) symptoms with transient white matter lesions in the brain. PatientsWe describe a man with CMTX who presented with transient CNS symptoms and abnormal cerebral white matter lesions in MRI. He was subjected to a detailed MRI examination using two specialized techniques, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). ResultsIn the early stage of his CNS symptoms, MRS studies revealed reduced N-acetyl-aspartate (NAA) levels in deep white matter, and DTI revealed reduced fractional anisotropy within lesions. Interestingly, these reductions began to recover from day 19 after admission, and follow-up DTI and MRS studies on day 101 revealed a reversal of the abnormalities. ConclusionThe findings of reversible reductions in fractional anisotropy and NAA levels in our patient suggest reversible axonal damage associated with deficient oligodendrocyte gap junctions.

Exploring white matter microstructure

White matter, occupying approximately half the brain, has only lately begun to receive the attention justified by its volume. Normal anatomy remains incompletely understood, although recent work has added to our knowledge,1 and a major impediment to progress has been a lack of sensitive methods for analyzing white matter in vivo. As a result, clinicians have become accustomed to seeing white matter on CT or MRI as a homogeneous tissue mass next to gray matter and ventricles from which little can be gleaned about regional variation or functional affiliation. Similarly, although some MRI white matter lesions are diagnostically useful, the clinical significance of many neuroimaging findings often remains unclear. With the recent arrival of diffusion tensor imaging (DTI),2 an MRI technique that can assess the degree of white matter tract organization using a measure known as fractional anisotropy (FA), more sophisticated analyses are possible, and both neuroanatomy and pathology can be better appreciated. In this issue of Neurology ®, Lee et al.3 present …

Sertraline Improves Executive Function in Patients With Vascular Cognitive Impairment

The authors reviewed 35 open-label sertraline trials for executive impairment in ischemic cerebrovascular disease. Outcomes included clock-drawing, the Executive Interview (EXIT25), the Geriatric Depression Scale, and the Mini-Mental State Examination. Clinically "meaningful" improvement was defined as a >3.0 EXIT25 point decline from baseline. "Remission" was defined as the achievement of an EXIT25 score <15/50. Only EXIT25 scores improved significantly. Twenty patients (57.1%) experienced a clinically meaningful improvement in executive control function. Twelve (34.3%) achieved remission. Our findings suggest that sertraline may have both statistical and clinically meaningful effects on executive control function in ischemic cerebrovascular disease. The authors discuss the implications for future clinical trials.

Effects of a Cyclooxygenase-2 Preferential Inhibitor in Young Healthy Dogs Exposed to Air Pollution: A Pilot Study

Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentrations of prostaglandin E2 metabolite and the oligomeric form of amyloid derived diffusible ligand; measured the mRNA expression of cyclooxygenase-2, interleukin 1beta, CD14, and Aquaporin-4 in target brain areas; and evaluated brain MRI, cognition, and neuropathology in 8 dogs treated with a preferential cyclooxygenase-2 inhibitor (Nimesulide) versus 7 untreated litter-matched Mexico City dogs. Nimesulide significantly decreased nitrotyrosine in plasma (p < .0001), frontal gray IL1beta (p = .03), and heart IL1beta (p = .02). No effect was seen in mRNA COX2, amyloid, and PGE2 in CSF or the MRI white matter lesions. All exposed dogs exhibited olfactory bulb and frontal accumulation of Abeta(42) in neurons and blood vessels and frontal vascular subcortical pathology. White matter hyperintense MRI frontal lesions were seen in 4/6 non-treated and 6/8 treated dogs. Nonsteroidal anti-inflammatory drugs may offer limited neuroprotection in the setting of severe air pollution exposures. The search for potentially beneficial drugs useful to ameliorate the brain effects of pollution represents an enormous clinical challenge.

MRI surrogates for vascular dementia trials

There is neuropathological evidence that confluent MRI white matter lesions, lacunes and cerebral microbleeds in the elderly reflect ischemic brain damage due to microangiopathy. It has been suggested that MRI may be used to monitor treatment trials on subcortical vascular dementia. A prerequisite for the use of any small vessel disease-related brain abnormality as surrogate marker is longitudinal change allowing detection of treatment effects within a reasonable time period and correlation with cognitive decline.

Etiological profile of presumptive optic neuritis in China

To determine the diagnoses in a population of patients with presumed optic neuritis (ON) in China and compare the spectrum of etiologies with those in western countries, we studied a group of 204 patients referred to a teaching hospital with a presumptive diagnosis of ON. We conducted detailed medical and family history, thorough ophthalmologic and neurological examinations, and laboratory tests including neuroimaging. Patients were diagnosed using international diagnostic criteria. One hundred and thirteen patients (55.4%) met ON criteria, among whom 83 patients (73.5%) were diagnosed with idiopathic demyelinating optic neuritis (IDON). Brain MRI white matter lesions were found in 11 of 78 (14.1%) clinically “isolated” IDON patients. Tuberculosis meningitis was found in 2 patients and syphilis in 1 patient. The cause of ON in 26 patients (23.0%) remained uncertain, but it was still likely to be IDON accompanied by secondary axonal degeneration. Leber’s hereditary optic neuropathy (LHON) was found in 38 patients (18.6%), confirmed by mitochondrial DNA point mutation screening. Seventeen patients (8.3%) had ischemic optic neuropathy. A spectrum of other entities mimicked ON. Therefore, idiopathic demyelinating ON was the most common type of optic neuropathy in our group. Despite minor differences regarding the causes and prognosis, the etiology of ON in our population is similar to that reported in Western countries.

P2.037 Association between balance impairment, falls and agerelated white matter lesions in MRI: a population based Age, Gene/Environment Susceptibility-Reykjavik Study

P2.037 Association between balance impairment, falls and agerelated white matter lesions in MRI: a population based Age, Gene/Environment Susceptibility-Reykjavik Study

MRI white Matter Lesions in a Stroke Clinic Population: Correlation with Increased Carotid Intima-media Thickness on Ultrasonography

Cerebral white matter lesions (WML) on MRI have been related not only to age but also to cerebrovascular disorders. This study aimed to determine the prevalence of WML in a population of patients attending a stroke clinic and relate it to the presence of carotid atherosclerosis as determined by increased carotid intima-media thickness (IMT) on ultrasonography. Subjects were recruited from patients attending a stroke clinic at the National Hospital for Neurology and Neurosurgery, Queen square, London. The patients had cranial MRI and carotid ultrasonography (amongst other investigations). WML on MRI were graded according to the rating scale of the Task force on age-related white matter changes and a WML score was obtained based on the WML grades and geographical distribution. Patients with carotid intima-media thickness > 1cm on ultrasonography were considered to have increased intima-media thickness. WML was present in 63.46% of subjects. Patients with WML had a significantly higher mean age than those without (67.5 vs 53.5 years). Increased carotid IMT was found in 33.3% of those with WML and in 15.8% of those without. The difference was not statistically significant. There was no significant association between the presence of any grade of WML and increased carotid IMT. Similarly, the mean WML scores for patients with and without increased carotid IMT were not significantly different. A high proportion of patients in the stroke clinic had WML on MRI. Presence of WML was not associated with the presence of carotid atherosclerosis as shown by increased carotid intima-media thickness. Nigerian Medical Practitioner Vol. 52 (2) 2007: pp. 38-41

The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28-May 5, 2007

The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28-May 5, 2007

White Matter Lesions in an Unselected Cohort of the Elderly

Background and Purpose— “Incidental” MRI white matter (WM) lesions, comprising periventricular lesions (PVLs) and deep subcortical lesions (DSCLs), are common in the aging brain. Direct evidence of ischemia associated with incidental WM lesions (WMLs) has been lacking, and their pathogenesis is unresolved. Methods— A population-based, postmortem cohort (n=456) of donated brains was examined by MRI and pathology. In a subsample of the whole cohort, magnetic resonance images were used to sample and compare WMLs and nonlesional WM for molecular markers of hypoxic injury. Results— PVL severity was associated with loss of ventricular ependyma ( P =0.004). For DSCLs, there was arteriolar sclerosis compared with normal WM (vessel wall thickness and perivascular enlargement; both P &lt;0.001). Capillary endothelial activation (ratio of intercellular adhesion molecule to basement membrane collagen IV; P &lt;0.001) and microglial activation (CD68 expression; P =0.002) were elevated in WMLs. Immunoreactivity for hypoxia-inducible factors (HIFs) HIF1α and HIF2α was elevated in DSCLs ( P =0.003 and P =0.005). Other hypoxia-regulated proteins were also increased in WMLs: matrix metalloproteinase-7 (PVLs P &lt;0.001; DSCLs P =0.009) and the number of neuroglobin-positive cells (WMLs P =0.02) reaching statistical significance. The severity of congophilic amyloid angiopathy was associated with increased HIF1α expression in DSCLs ( P =0.04). Conclusion— The data support a hypoxic environment within MRI WMLs. Persistent HIF expression may result from failure of normal adaptive mechanisms. WM ischemia appears to be a common feature of the aging brain.