T2-hyperintense White Matter Lesions Research Articles

Effects of fingolimod on focal and diffuse damage in patients with relapsing-remitting multiple sclerosis - The "EVOLUTION" study.

In multiple sclerosis (MS), MRI markers can measure the potential neuroprotective effects of fingolimod beyond its anti-inflammatory activity. In this study we aimed to comprehensively explore, in the real-word setting, whether fingolimod not only reduces clinical/MRI inflammatory activity, but also influences the progression of irreversible focal and whole brain damage in relapsing-remitting [RR] MS patients. The "EVOLUTION" study, a 24-month observational, prospective, single-arm, multicenter study, enrolled 261 RRMS patients who started fingolimod at 32 Italian MS centers and underwent biannual neurological assessments and annual MRI evaluations. Study outcomes included the proportions of evaluable RRMS patients achieving at 24months: (1) no new/enlarging T2-hyperintense white matter (WM) lesions and/or clinical relapses; (2) a modified classification of "No Evidence of Disease Activity 4" ("modified NEDA-4") defined as no new/enlarging T2-hyperintense WM lesions, clinical relapses, and 6-month confirmed disability progression, and a yearly percentage lateral ventricular volume change on T2-FLAIR images < 2%; (3) less than 40% of active lesions at baseline and month 12 evolving to permanent black holes (PBHs). At month 24, 76/160 (47.5%; 95% confidence interval [CI] = 39.8%;55.2%) RRMS patients had no clinical/MRI activity. Thirty-nine of 170 RRMS patients (22.9%; 95% CI = 16.6%;29.3%) achieved "modified NEDA-4" status. Forty-four of 72 RRMS patients (61.1%; 95% CI = 49.8%;72.4%) had less than 40% of active WM lesions evolving to PBHs. The study confirmed the established safety and tolerability profile of fingolimod. By comparing our results with those from the literature, the EVOLUTION study seems to indicate a neuroprotective effect of fingolimod, limiting inflammatory activity, brain atrophy and PBH development.

Low-frequency MR elastography reveals altered deep gray matter viscoelasticity in multiple sclerosis

IntroductionBrain viscoelasticity as assessed by magnetic resonance elastography (MRE) has been discussed as a promising surrogate of microstructural alterations due to neurodegenerative processes. Existing studies indicate that multiple sclerosis (MS) is associated with a global reduction in brain stiffness. However, no study to date systematically investigated the MS-related characteristics of brain viscoelasticity separately in normal-appearing white matter (NAWM), deep gray matter (DGM) and T2-hyperintense white matter (WM) lesions. Methods70 MS patients and 42 healthy volunteers underwent whole-cerebral MRE using a stimulated echo sequence (DENSE) with a low-frequency mechanical excitation at 20 Hertz. The magnitude |G∗| (Pa) and phase angle φ (rad) of the complex shear modulus G∗ were reconstructed by multifrequency dual elasto-visco (MDEV) inversion and related to structural imaging and clinical parameters. ResultsWe observed φ in the thalamus to be higher by 4.3 % in patients relative to healthy controls (1.11 ± 0.07 vs. 1.06 ± 0.07, p < 0.0001). Higher Expanded Disability Status Scale (EDSS) scores were negatively associated with φ in the basal ganglia (p = 0.01). We measured φ to be lower in MS lesions compared to surrounding NAWM (p = 0.001), which was most prominent for lesions in the temporal lobe (1.01 ± 0.22 vs. 1.06 ± 0.19, p = 0.003). Age was associated with lower values of |G∗| (p = 0.04) and φ (p = 0.004) in the thalamus of patients. No alteration in NAWM stiffness relative to WM in healthy controls was observed. ConclusionLow-frequency elastography in MS patients reveals age-independent alterations in the viscoelasticity of deep gray matter at early stages of disease.

Diagnostic Performance of Cortical Lesions and the Central Vein Sign in Multiple Sclerosis

Multiple sclerosis (MS) misdiagnosis remains an important issue in clinical practice. To quantify the performance of cortical lesions (CLs) and central vein sign (CVS) in distinguishing MS from other conditions showing brain lesions on magnetic resonance imaging (MRI). This was a retrospective, cross-sectional multicenter study, with clinical and MRI data acquired between January 2010 and May 2020. Centralized MRI analysis was conducted between July 2020 and December 2022 by 2 raters blinded to participants' diagnosis. Participants were recruited from 14 European centers and from a multicenter pan-European cohort. Eligible participants had a diagnosis of MS, clinically isolated syndrome (CIS), or non-MS conditions; availability of a brain 3-T MRI scan with at least 1 sequence suitable for CL and CVS assessment; presence of T2-hyperintense white matter lesions (WMLs). A total of 1051 individuals were included with either MS/CIS (n = 599; 386 [64.4%] female; mean [SD] age, 41.5 [12.3] years) or non-MS conditions (including other neuroinflammatory disorders, cerebrovascular disease, migraine, and incidental WMLs in healthy control individuals; n = 452; 302 [66.8%] female; mean [SD] age, 49.2 [14.5] years). Five individuals were excluded due to missing clinical or demographic information (n = 3) or unclear diagnosis (n = 2). MS/CIS vs non-MS conditions. Area under the receiver operating characteristic curves (AUCs) were used to explore the diagnostic performance of CLs and the CVS in isolation and in combination; sensitivity, specificity, and accuracy were calculated for various cutoffs. The diagnostic importance of CLs and CVS compared to conventional MRI features (ie, presence of infratentorial, periventricular, and juxtacortical WMLs) was ranked with a random forest model. The presence of CLs and the previously proposed 40% CVS rule had a sensitivity, specificity, and accuracy for MS of 59.0% (95% CI, 55.1-62.8), 93.6% (95% CI, 91.4-95.6), and 73.9% (95% CI, 71.6-76.3) and 78.7% (95% CI, 75.5-82.0), 86.0% (95% CI, 82.1-89.5), and 81.5% (95% CI, 78.9-83.7), respectively. The diagnostic performance of the CVS (AUC, 0.89 [95% CI, 0.86-0.91]) was superior to that of CLs (AUC, 0.77 [95% CI, 0.75-0.80]; P < .001), and was increased when combining the 2 imaging markers (AUC, 0.92 [95% CI, 0.90-0.94]; P = .04); in the random forest model, both CVS and CLs outperformed the presence of infratentorial, periventricular, and juxtacortical WMLs in supporting MS differential diagnosis. The findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.

Functional and structural brain MRI changes associated with cognitive worsening in multiple sclerosis: a 3-year longitudinal study.

Heterogeneous processes may contribute to cognitive impairment in multiple sclerosis (MS). To apply a longitudinal multiparametric MRI approach to identify mechanisms associated with cognitive worsening in MS patients. 3T brain functional and structural MRI scans were acquired at baseline and after a median follow-up of 3.4years in 35 MS patients and 22 healthy controls (HC). Associations between cognitive worsening (reliable change index score < -1.25 at the Rao's battery) and longitudinal changes in regional T2-hyperintense white matter (WM) lesions, diffusion tensor microstructural WM damage, gray matter (GM) atrophy and resting state (RS) functional connectivity (FC) were explored. At follow-up, HC showed no clusters of significant microstructural WM damage progression, GM atrophy or changes in RS FC. At follow-up, 10 MS patients (29%) showed cognitive worsening. Compared to cognitively stable, cognitively worsened MS patients showed more severe GM atrophy of the right anterior cingulate cortex and bilateral supplementary motor area (p < 0.001). Cognitively worsened vs cognitively stable MS patients showed also decreased RS FC in the right hippocampus of the right working memory network and in the right insula of the default mode network. Increased RS FC in the left insula of the executive control network was found in the opposite comparison (p < 0.001). No significant regional accumulation of focal WM lesions nor microstructural WM abnormalities occurred in both patients' groups. GM atrophy progression in cognitively relevant brain regions combined with functional impoverishment in networks involved in cognitive functions may represent the substrates underlying cognitive worsening in MS.

Dots and spots: A retrospective review of T2-hyperintense white matter lesions in pediatric patients with and without headache.

We aimed to determine if T2-weighted hyperintense white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) occur more frequently in pediatric patients with migraine and other primary headache disorders compared to the general pediatric population. Small foci of T2 hyperintensity in the white matter are frequently identified on brain MRI during the workup of pediatric headache. Such lesions have been reported to be more common among adults with migraine versus adults without migraine; however, this association has not been well established in the pediatric population. We performed a retrospective cross-sectional single-center study of electronic medical records and radiologic studies, examining pediatric patients from 3 to 18 years old who underwent brain MRI between 2016 and 2021. Patients with existing intracranial disease or abnormalities were excluded. Patients with reports of headache were categorized. Imaging was reviewed to determine the number and location of WMLs. Headache-associated disability scores (Pediatric Migraine Disability Assessment) were noted, when available. Brain MRI of 248 patients with a diagnosis of headache (144 with migraine, 42 with non-migraine primary headache, and 62 with headache that could not be further classified) and 490 controls were reviewed. WMLs were encountered commonly among all study participants, with a prevalence of 40.5% (17/42) to 54.1% (265/490). There was no statistically significant difference comparing the number of lesions between each of the headache groups and the control group: migraine group versus control group median [interquartile range (IQR)], 0 [0-3] versus 1 [0-4], incidence rate ratio [95% confidence interval (CI)], 0.99 [0.69-1.44], p = 0.989, non-migraine headache group versus control group median [IQR], 0 [0-3] versus 1 [0-4], 0.71 [0.46-1.31], p = 0.156, headache not otherwise specified group versus control group median [IQR], 0 [0-4] versus 1 [0-4], 0.77 [0.45-1.31], p = 0.291. There was no significant correlation between headache-associated disability and the number of WMLs (0.07 [-0.30 to 0.17], rho [95% CI]). T2 hyperintense WMLs are common within the pediatric population and are not encountered more frequently in pediatric patients with migraine or other primary headache disorders. Thus, such lesions are presumably incidental and unlikely related to headache history.

Abruptly Stopping an Adamantane Management for Fatigue in an Elderly Multiple Sclerosis Patient Provoked Acute Withdrawal Symptoms (AWS); A Case Report

Introduction: Health care workers are continuously being burdened with acute conditions especially with the current pandemic of Covid-19. Staying home and feeling trapped can be particularly detrimental to patients with history of depression or psychotic as well as multiple sclerosis. We present a case of a 63-year-old patient with Multiple Sclerosis whose condition is being managed with mainly dopamine agonists. Withdrawal symptoms arose acutely after abrupt cessation of Amantadine; a dopamine agonist. Amantadine is thought to work by raising the amount of dopamine available to brain cells. The purpose of this research is to report a case of a 63-yearold Multiple Sclerosis patient who presented with Acute Withdrawal Syndrome (AWS) after being managed with Amantadine for two years and abruptly stopping the medication. Case Presentation: A 63-year-old woman with past medical history of stroke and multiple sclerosis reported symptoms of AWS after abruptly stopping amantadine use for multiple sclerosis. The patient was on cyclobenzaprine for spasticity, gabapentin and lamotrigine for neuropathic pain and seizure disorder respectively. She also had a history of hypertension and hyperlipidemia and presented with 1-week history of nausea and vomiting followed by visual hallucination, tremor, slurred speech and lethargy. On presentation, the patient was afebrile and hemodynamically stable. This patient denies blurred vision and severe fatigue with bathing or exercise. Upon further evaluation, patient did not report electrical sensation down her limbs or back especially with neck flexion. The initial labs were remarkable for hemoglobin of 8.5mg/dL and hypokalemia of 3.2mmol/L. We suspected vasculitis of CNS. One of the proposed pathophysiology for this is the extensive inflammatory damage to the blood brain barrier, allowing inflammatory cell recruitment into the CNS. The patient was admitted for acute altered mental status with waxing and wanning symptoms. Her acute delirium symptoms lead to the withdrawal of amantadine and cyclobenzaprine. Within about 48-70 hours later, patient developed severe agitation requiring emergent intubation. EEG showed generalized medium voltage delta, theta, and fast activity throughout indicative of diffuse cerebral dysfunction, but no lateralized or epileptic activity was seen. CT brain was negative for acute stroke or bleed. The patient underwent lumbar puncture, and was started on empiric coverage with IV acyclovir, vancomycin, and ceftriaxone for possible meningoencephalitis along with methylprednisolone for possible multiple sclerosis flare vs autoimmune encephalitis. MRI showed stable extensive white matter T2 hyperintense lesions. CSF was negative for infectious processes, and vancomycin, ceftriaxone, and acyclovir were discontinued. The patient continued to require sedation for severe agitation. The severe agitation was suspected to be due to discontinuation of her home medications, one of which was amantadine. The amantadine was resumed with improvement of her mental status within 24 hours. Patient was extubated within 48 hours of initiation of amantadine and was transferred to the floor for continuity of care and eventually discharged home after 15 days of hospitalization. Conclusion: Acute Withdrawal Syndrome (AWS) symptoms are often as a result of abrupt cessation of a medication(s) particularly central acting agents like clonidine, beta adrenergic antagonists as well as diuretics but Amantadine is starting to be a strong culprit since it is also thought to act centrally as a dopamine agonist. Clinicians should always be mindful of AWS especially from patients on long term central acting medications that have been abruptly stopped.

Abstract P499: The Effect of Small Vessel Disease Burden on Core/Penumbra Mismatch and Outcomes in Extended Window Thrombectomy

Objective: Recent studies have shown the benefit of revascularization in select patients with extended window large vessel occlusion (EWLVO). We sought to assess the effect of cerebral small vessel disease (CSVD) burden on eligibility for intervention with mechanical thrombectomy (MT) and functional outcomes in patients with EWLVO. Methods: We conducted a retrospective single-center study of 135 patients with anterior circulation LVO who presented in the extended time window, 6 to 24 hours from LKW, between August 2018 and March 2020. All patients underwent perfusion imaging at initial presentation and those with target ischemic core to penumbra mismatch profiles, as defined by DAWN/DEFUSE3 criteria, were treated with MT. Included patients were evaluated for CSVD burden using T2-FLAIR MRI. The Fazekas scale (0-3) was used to quantify the amount of white matter T2 hyperintense lesions in both the periventricular (PVWM) and deep white matter (DWM). Patients’ functional outcomes were assessed at 90 days using the mRS. Multivariate ordinal logistic regression models were used and adjusted for age, gender, thrombus location and LKW to perfusion imaging time. Patient information was collected from the Houston Methodist Hospital Outcomes Based Prospective Endpoints in Stroke (HOPES) registry. Results: Of the 135 patients, 111 met imaging inclusion criteria for revascularization with MT for EWLVO. MT was deferred in 44 of these patients due to other clinical exclusions or patient refusal. Patients ineligible for MT were approximately 13 times more likely to have a higher PVWM Fazekas grade (OR =13.53, 95% CI. [2.94 - 62.39], p=0.001) and 17 times more likely to have a higher DWM Fazekas grade (OR =17.54, 95% CI. [4.20 - 73.17], p&lt;0.001), when compared to patients who were eligible for MT. Patients who did not meet criteria for MT were nearly 7 times more likely to have poor functional outcomes at 90 days (OR =6.85, 95% CI. [2.09 - 22.44], p=0.001). Conclusion: Based on our analytical cohort of EWLVO patients, those with severe CSVD burden were more likely to be excluded from MT and had worse functional outcomes. Poor cerebrovascular reserve and diminished collateral flow leading to rapid infarct progression in patients with greater CSVD burden may be a potential explanation.

Semi-automatic detection of increased susceptibility in multiple sclerosis white matter lesions imaged with 1.5T MRI

ObjectiveThe identification of regions of increased susceptibility (RoIS) in multiple sclerosis (MS) white matter lesions (WML) is currently performed by the radiologist’s visual inspection of magnetic resonance imaging (MRI) data acquired with high-field MRI scanners. The aims of this study were: 1) to define and validate a semi-automatic method for detecting RoIS in WML from quantitative susceptibility maps (QSM) and susceptibility-weighted imaging (SWI) acquired with a 1.5 T MRI scanner; 2) to assess the prevalence of WML with RoIS and the susceptibility in those areas; and 3) to test the association between RoIS in WML and clinical outcomes. MethodsThirty-eight MS patients were scanned on a 1.5 T MRI scanner. T2-hyperintense WML were segmented and superimposed on SWI and QSM images. Two intensity thresholds were defined and consecutively applied for identifying RoIS within WML (thrhyper_QSM to identify QSM hyperintensity within WML and thrhypoSWI to identify SWI hypointensity within WML). The sensitivity and specificity were assessed on a subgroup of subjects. The numbers of WML with RoIS and RoIS volume were determined. Differences between phenotypes and correlations with clinical outcome were tested. ResultsThe method showed good sensitivity (95.6%) and specificity (92.1%). On average, 44.7% of the WML showed RoIS, occupying 11.0% of the total lesion volume, with an average susceptibility of 39.4 ± 12.2 ppb. The number of WML with RoIS was negatively correlated with disease duration (r = −0.342, p = 0.035). ConclusionThe proposed semi-automatic method proved to be suitable for the detection of RoIS in WML at 1.5 T. This approach may be useful in longitudinal studies aiming to monitor susceptibility in WML.

Prognostic value of white matter lesion shrinking in early multiple sclerosis: An intuitive or naïve notion?

Background and purposeNew or enlarging T2‐hyperintense white matter lesions (WML) are associated with clinical disease progression in multiple sclerosis (MS). The prognostic value of WML shrinking is unclear. Assuming that waning of acute inflammation and repair processes would be the main drivers of WML shrinking, we aimed to assess the prognostic value of WML shrinking in early MS.MethodsWe retrospectively analyzed a cohort of 144 early MS patients with three brain MRI scans at baseline and after 1 and 3 years available. All patients were therapy naïve at baseline and 70.5% of them treated with disease modifying drugs at year 1. We determined the volume of WML shrinking between MRI scans, total WML volumes, number of gadolinium‐enhancing and new WML, white matter (WM) and gray matter volumes at each MRI scan. Clinical disability was measured by Expanded Disability Status Scale. We performed the correlation analyses of WML shrinking with other MRI parameters and clinical outcome.ResultsWhite matter lesions shrinking was highly variable between patients and correlated with the initial number of gadolinium‐enhancing WML and with WM volume decrease. WML shrinking was not associated with clinical outcome.ConclusionWe found no indication of a prognostic value of WML shrinking in early MS patients. WML shrinking seems to be related to waning of acute inflammation.

Magnetic Resonance Imaging Characteristics of Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is arare hereditary disease presenting with distinct imaging features in middle-aged adults. This article describes the typical imaging features focusing on the longitudinal course of RVCL-S lesions. In this study six subjects (five male, five related) with RVCL-S were retrospectively included from two university hospitals. The median age of symptom onset was 40 ± 6years. Magnetic resonance imaging (MRI) covering baseline and amedian follow-up period of 33months was reviewed in astructured way focusing on morphology, contrast enhancement and diffusion restriction of brain lesions. All patients showed patchy, T2 hyperintense white matter lesions (mean number 7.7 ± 1.8) with aperiventricular predominance at the frontal lobes (59%). In all subjects, rim-enhancing white matter lesions with temporary diffusion restriction were present for a mean of 5.0 ± 3.9months. Median duration of blood brain barrier disruption was 20months. Periventricular patchy white matter lesions in the frontal lobes as well as rim-enhancing lesions with prolonged diffusion restriction and long-lasting contrast enhancement are characteristic imaging findings in RCVL-S and can be helpful in the differential diagnosis.

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Quantitative dynamic contrast-enhanced MR imaging shows widespread blood-brain barrier disruption in mild traumatic brain injury patients with post-concussion syndrome.

To explore the utility of dynamic contrast-enhanced (DCE) MR imaging for quantitative analysis of blood-brain barrier disruption in mild traumatic brain injury (mTBI) patients with post-concussion syndrome (PCS). Forty-four consecutive patients with PCS after mTBI and 32 controls were included in this retrospective study. Ktrans and ve from DCE MR imaging were analyzed at contrast-enhancing lesions, T2 hyperintense white matter (WM) lesions, normal-appearing white matter (NAWM), and predilection sites for diffuse axonal injury (LocationDAI). The Mann-Whitney U-test was performed to compare the parameters between mTBI patients and controls and the parameters were correlated with neuropsychological tests using Mann-Whitney U-test and Spearman rank correlation. The median ve of the T2 hyperintense WM lesions in mTBI patients (n=21) was higher than that of NAWM in controls (p=.027). Both median Ktrans and ve at NAWM were also significantly higher in mTBI patients than in controls (p=.023 and p=.029, respectively). In addition, mTBI patients had higher Ktrans and ve at LocationDAI than controls (p=.008 and p=.015, respectively). VLT (delayed recall) scores were significantly correlated with ve values at T2 hyperintense WM lesions (p=-0.767, p=.044). The median ve at LocationDAI was significantly higher in patients with atypical performance in the digit span test (forward) than in those with average or good performance (p=.043). mTBI patients with PCS had higher Ktrans and ve values than controls not only at T2 hyperintense WM lesions but also at NAWM and LocationDAI. BBB disruption may be implicated in development of PCS in mTBI patients. • mTBI patients with PCS had higher permeability than controls at T2 hyperintense WM lesions on DCE MR imaging. • mTBI patients with PCS had higher permeability than controls also at NAWM and predilection sites for DAI. • BBB disruption may be implicated in the development of PCS in mTBI patients.

Clinical profile and neuroimaging in pediatric optic neuritis in Indian population: A case series.

Purpose of the study:The purpose of this study was to report clinical features, neuroimaging, and visual outcome in pediatric optic neuritis (ON) in Indian population.Materials and Methods:This is a retrospective study of children up to the age of 16 years, diagnosed with ON, that presented at pediatric and neuroophthalmology clinic of a tertiary eye care center, in South India, within the period of 2010–2015.Results:We identified 62 eyes of 40 children diagnosed as ON within the study period. The mean age was 11.15 ± 3.24 years (1–15 years) with mean follow-up of 13 months. In this series, there was female preponderance (67%). Mean logarithm of the minimum angle of resolution visual acuity at presentation was 1.14 ± 0.93, which after treatment recovered to 0.10 ± 0.26 at final visit (P < 0.001). Involvement was bilateral in 22 children (55%) and recurrent in 3 eyes of 3 children. Preceding febrile illness was reported in seven cases (18%). Four (10%) cases were diagnosed as multiple sclerosis (MS), one with neuromyelitis optica, and one with acute disseminated encephalomyelitis. One case was associated with tuberculous meningitis, 1 with septicemia, and 1 with bilateral maxillary sinusitis. Neuroimaging studies of optic nerve in 14 children demonstrated isolated optic nerve enhancement. Magnetic resonance imaging brain revealed white matter T2 hyperintense lesions separate from optic nerve in ten cases, of which four cases were diagnosed as MS.Conclusions:Bilateral presentation was common, association with MS was low. Papillitis was more frequent than retrobulbar neuritis and prognosis was good in pediatric ON in Indian population.

Acute Delirium and Sub-acute Cognitive Decline in a Patient with Probable Cerebral Amyloid Angiopathy Related Inflammation

Cerebral amyloid angiopathy (CAA) is a well-known pathology of Alzheimer’s disease among elderly individuals. CAA-related inflammation (CAAri) has been increasingly viewed as a rare presentation of CAA. We report the case a 65-year-old man who presented with subacute dementia and reversible delirium secondary to probable CAAri. His laboratory findings were negative except for elevated cerebrospinal fluid protein levels. Brain magnetic resonance imaging (MRI) revealed disseminated microbleeds in both the cerebral hemispheres on T2 weighted gradient images and prominent confluent T2-hyperintense white matter lesions in the bilateral temporo-occipital subcortical areas. Suspecting CAAri, we prescribed steroid pulse therapy with oral steroid tapering. The acute delirium and agitation improved after medication. However, the CAAri-induced damage to the brain function persisted, as evidenced in the follow-up clinical performance and serial Mini-Mental State Examination (MMSE). The identification and accurate diagnosis of CAAri are important because the disease may respond to immunosuppressive therapy. In clinical settings, the detection of CAA with diffuse microbleeds in the brain is essential for making a tentative diagnosis of CAAri. Immunosuppressive therapy is the cornerstone of treatment. However, the optimal treatment duration is currently uncertain and warrants further investigation. In conclusion, the possible diagnosis of CAAri should always be considered when a patient presents with sub-acute cognitive decline and compatible MRI findings (T2-hyperintense lesions with diffuse microbleeds).

Brain unidentified bright objects ("UBO") in systemic lupus erythematosus: sometimes they come back. A study of microembolism by cMRI and Transcranial Doppler ultrasound.

The objectives of this report are to assess the occurrence of microembolic signals (MES) detected by transcranial Doppler ultrasound (TCD) in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (SLE) neuropsychiatric involvement, and to verify the correlation between MES, clinical characteristics, especially the patent foramen ovale (PFO), and the presence of punctuate T2-hyperintense white matter lesions (WMHLs) detected by conventional magnetic resonance imaging (cMRI). A TCD registration to detect MES from the middle cerebral artery was carried out in SLE and NPSLE patients after exclusion of aortic and/or carotid atheromatous disease. In all patients conventional brain magnetic resonance imaging (cMRI) and transesophageal echocardiography were performed. Patients were stratified in two groups, with and without WMHLs, and compared. Twenty-three SLE patients (16 NPSLE and seven SLE) were enrolled in the study. Overall MES were detected in 12 patients (52.1%), WHMLs were detectable in 15 patients (13 NPSLE and two SLE) while eight patients had normal cMRI (three NPSLE and five SLE). Matching TCD ultrasound and neuroimaging data, MES were detected in 10 (nine NPSLE and one SLE) out of 15 patients with WHMLs and in only two out of eight patients (two NPSLE and six SLE) with normal cMRI, both with NP involvement. A PFO was confirmed in all cases of MES detection. MES are frequent findings in SLE patients, especially in those with focal WMHLs detected by cMRI and correlating with PFO. These findings should be taken into account and suggest caution in the interpretation of cMRI pictures along with a careful evaluation of MES in patients with cMRI abnormalities that should be included in the workup of SLE patients.

MR Imaging Evaluation of Intracerebral Hemorrhages and T2 Hyperintense White Matter Lesions Appearing after Radiation Therapy in Adult Patients with Primary Brain Tumors.

The purpose of our study was to determine the frequency and severity of intracerebral hemorrhages and T2 hyperintense white matter lesions (WMLs) following radiation therapy for brain tumors in adult patients. Of 648 adult brain tumor patients who received radiation therapy at our institute, magnetic resonance (MR) image data consisting of a gradient echo (GRE) and FLAIR T2-weighted image were available three and five years after radiation therapy in 81 patients. Intracerebral hemorrhage was defined as a hypointense dot lesion appearing on GRE images after radiation therapy. The number and size of the lesions were evaluated. The T2 hyperintense WMLs observed on the FLAIR sequences were graded according to the extent of the lesion. Intracerebral hemorrhage was detected in 21 (25.9%) and 35 (43.2) patients in the three- and five-year follow-up images, respectively. The number of intracerebral hemorrhages per patient tended to increase as the follow-up period increased, whereas the size of the intracerebral hemorrhages exhibited little variation over the course of follow-up. T2 hyperintense WMLs were observed in 27 (33.3%) and 32 (39.5) patients in the three and five year follow-up images, respectively. The age at the time of radiation therapy was significantly higher (p < 0.001) in the patients with T2 hyperintense WMLs than in those without lesions. Intracerebral hemorrhages are not uncommon in adult brain tumor patients undergoing radiation therapy. The incidence and number of intracerebral hemorrhages increased over the course of follow-up. T2 hyperintense WMLs were observed in more than one-third of the study population.

Longitudinal Patch-Based Segmentation of Multiple Sclerosis White Matter Lesions.

Segmenting T2-hyperintense white matter lesions from longitudinal MR images is essential in understanding progression of multiple sclerosis. Most lesion segmentation techniques find lesions independently at each time point, even though there are different noise and image contrast variations at each point in the time series. In this paper, we present a patch based 4D lesion segmentation method that takes advantage of the temporal component of longitudinal data. For each subject with multiple time-points, 4D patches are constructed from the T1-w and FLAIR scans of all time-points. For every 4D patch from a subject, a few relevant matching 4D patches are found from a reference, such that their convex combination reconstructs the subject's 4D patch. Then corresponding manual segmentation patches of the reference are combined in a similar manner to generate a 4D membership of lesions of the subject patch. We compare our 4D patch-based segmentation with independent 3D voxel-based and patch-based lesion segmentation algorithms. Based on ground truth segmentations from 30 data sets, we show that the mean Dice coefficients between manual and automated segmentations improve after using the 4D approach compared to two state-of-the-art 3D segmentation algorithms.

Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease.

Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm(2). ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm(2) which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) × 10(-3) mm(2)/s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) × 10(-3) mm(2)/s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) × 10(-3) mm(2)/s in MS patients, and (0.75 ± 0.08) × 10(-3) mm(2)/s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation.

Pneumococcal-meningitis associated acute disseminated encephalomyelitis (ADEM) - case report of effective early immunotherapy.

IntroductionUnvaccinated patients with history of splenectomy are prone to fulminant courses of Streptococcus pneumoniae-associated bacterial meningitis. Besides direct brain damage those patients may additionally suffer from parainfectious syndromes, notably vasculitis and acute disseminated encephalomyelitis (ADEM). Differentiation and treatment of these immunological reactions is challenging.MethodsCase report.ResultsA 61 year-old woman with history of splenectomy without vaccination for S. pneumoniae presented with progressive headache and meningism. CSF-analysis revealed pleocytosis with microbiological evidence for pneumococcal meningitis. After unsuspicious initial cranial CT imaging and initiation of appropriate antibiotic therapy, MRI two days later showed widespread FLAIR- and T2-hyperintense white matter lesions that further progressed upon follow-up MRI and that fulfilled imaging criteria of ADEM. Meanwhile the patient deteriorated and required mechanical ventilation. Cranial angiography showed no signs of vasculitis or vasospasms. Screening for autoimmune diseases remained negative, however oligoclonal bands turned positive. Brain biopsy mainly revealed perivascular CD4+ T-cells and demyelinated areas. Despite ongoing acute meningitis, a 10-day corticosteroid-pulse was initiated followed by steroid-tapering. Within 4 weeks, clinical and MRI findings ameliorated. In an one-year follow-up visit, the patient significantly recovered, MRI lesions were markedly reduced and no further relapses occurred.ConclusionAcute pneumococcal meningitis in unvaccinated splenectomized patients may be complicated by a monophasic course of parainfectious ADEM that can be controlled with high-dose corticosteroids. Parainfectious vasculitis or cerebritis are important differential diagnoses and exact differentiation of these entities is important to initiate early appropriate immunotherapy.

Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in a Japanese boy with recurrent optic neuritis

Myelin oligodendrocyte glycoprotein (MOG) localizes on the outermost surface of the myelin sheath and oligodendrocytes in the central nervous system (CNS). Autoantibodies against MOG are reportedly found in patients with spectrum of inflammatory demyelinating diseases of the CNS, including acute disseminated encephalomyelitis, multiple sclerosis, and neuromyelitis optica. In addition, recent studies have emphasized an association between anti-MOG antibodies and optic neuritis. We present the first case report of a 7-year-old Japanese boy who was positive for anti-MOG antibodies. He experienced four episodes of unilateral optic neuritis and one seizure event. Magnetic resonance imaging revealed T2-hyperintense lesions in the subcortical white matter and midbrain. Although he fulfilled the diagnostic criteria for multiple sclerosis, recombinant interferon beta did not prevent recurrence. Established cell-based immunoassays revealed that he was positive for anti-MOG antibodies and negative for anti-aquaporin 4 antibodies. Our case report supports the relationship between anti-MOG antibodies and recurrent optic neuritis. Additional studies are needed to establish the clinical significance of anti-MOG antibodies for diagnosis, treatment, and prognosis.