Subcortical White Matter Lesions Research Articles

Leukoaraiosis: Epidemiology, Imaging, Risk Factors, and Management of Age-Related Cerebral White Matter Hyperintensities.

Leukoaraiosis (LA) manifests as cerebral white matter hyperintensities on T2-weighted magnetic resonance imaging scans and corresponds to white matter lesions or abnormalities in brain tissue. Clinically, it is generally detected in the early 40s and is highly prevalent globally in individuals aged >60 years. From the imaging perspective, LA can present as several heterogeneous forms, including punctate and patchy lesions in deep or subcortical white matter; lesions with periventricular caps, a pencil-thin lining, and smooth halo; as well as irregular lesions, which are not always benign. Given its potential of having deleterious effects on normal brain function and the resulting increase in public health burden, considerable effort has been focused on investigating the associations between various risk factors and LA risk, and developing its associated clinical interventions. However, study results have been inconsistent, most likely due to potential differences in study designs, neuroimaging methods, and sample sizes as well as the inherent neuroimaging heterogeneity and multi-factorial nature of LA. In this article, we provided an overview of LA and summarized the current knowledge regarding its epidemiology, neuroimaging classification, pathological characteristics, risk factors, and potential intervention strategies.

The Microglial Transcriptome of Age-Associated Deep Subcortical White Matter Lesions Suggests a Neuroprotective Response to Blood-Brain Barrier Dysfunction.

Age-associated deep-subcortical white matter lesions (DSCLs) are an independent risk factor for dementia, displaying high levels of CD68+ microglia. This study aimed to characterize the transcriptomic profile of microglia in DSCLs and surrounding radiologically normal-appearing white matter (NAWM) compared to non-lesional control white matter. CD68+ microglia were isolated from white matter groups (n = 4 cases per group) from the Cognitive Function and Ageing Study neuropathology cohort using immuno-laser capture microdissection. Microarray gene expression profiling, but not RNA-sequencing, was found to be compatible with immuno-LCM-ed post-mortem material in the CFAS cohort and identified significantly differentially expressed genes (DEGs). Functional grouping and pathway analysis were assessed using the Database for Annotation Visualization and Integrated Discovery (DAVID) software, and immunohistochemistry was performed to validate gene expression changes at the protein level. Transcriptomic profiling of microglia in DSCLs compared to non-lesional control white matter identified 181 significant DEGs (93 upregulated and 88 downregulated). Functional clustering analysis in DAVID revealed dysregulation of haptoglobin-haemoglobin binding (Enrichment score 2.5, p = 0.017), confirmed using CD163 immunostaining, suggesting a neuroprotective microglial response to blood-brain barrier dysfunction in DSCLs. In NAWM versus control white matter, microglia exhibited 347 DEGs (209 upregulated, 138 downregulated), with significant dysregulation of protein de-ubiquitination (Enrichment score 5.14, p < 0.001), implying an inability to maintain protein homeostasis in NAWM that may contribute to lesion spread. These findings enhance understanding of microglial transcriptomic changes in ageing white matter pathology, highlighting a neuroprotective adaptation in DSCLs microglia and a potentially lesion-promoting phenotype in NAWM microglia.

Cephalalgic syndrome in autosomal dominant cerebral arteriopathy with subcortical infarctions and leucoencephalopathy

Background: Autosomal Dominant Cerebral Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is caused by mutations in NOTCH3 gene, classic symptoms include migraine with aura, ischemic strokes, apathy, depression and dementia. Headache is usually the first symptom, characterized by recurrent attacks of migraine with typical, hemiplegic or prolonged aura with unusual frequency. Material and methods: All the data were picked from the patient’s medical recordings. The patient had undergone a complete clinical exam, a contrast enhanced MRI-scan and a genetic test. Then a literature review was done based on the peculiarities of the case. Results: A 43-year-old woman presented with pulsatile, alternating, severe headache, accompanied by phono, and photophobia, nausea and vomiting, with an onset at 35 years and a frequency of 12/30, triggered by menstruation and stress, preceded by a day by a visual aura lasting 5-6 minutes. Family history revealed cases of stroke and migraine. Neurologic examination was normal, but a contrast enhanced MRI showed diffuse polymorph confluent subcortical white matter lesions, involving external capsule and anterior poles of the temporal lobes. NOTCH3 gene sequencing revealed the presence of a heterozygote missense c.421C&gt;T mutation, localized in the 4thexone. After establishing the diagnosis, the patient was prescribed a symptomatic treatment. Conclusions: Headache in CADASIL patients has well-defined diagnostic criteria in the International Classification of Headache Disorders, is being considered a secondary headache which may resemble or not migraine with aura. The patient presented a migraine-with-aura-like headache but with some peculiarities.

B - 105 Long COVID: a Pediatric Neuropsychological Case Study.

A neuropsychological case review of Long COVID. Long COVID remains to be a controversial topic in terms of cognitive residuals from contracting the virus. This child was referred due to acute cognitive changes post-COVID-19 contraction. Active COVID-19 infection was generally unremarkable. Patient did not require hospitalization or medication intervention. This patient is a 14-year-old, Caucasian, right-handed male. A psychiatrist referred the patient due to emotional (anxiety and oppositionality), cognitive (attention, reduced processing, memory, "brain fog,"), and physical (disrupted sleep, fatigue) changes post-infection. The diagnostic question was to rule out ADHD and oppositionality prior to obtaining MRI results. MRI of the brain, 30days post-infection, revealed multiple subcortical white matter lesions, located in the cerebral hemispheres near the grey-white matter junction, particularly in the frontal and parietal lobes. Patient was administered the Meyers Neuropsychological Battery (MNB). Findings were consistent with diffuse neuropsychological deficits, that is, reduced processing speed, impaired attention, and below average immediate and delayed memory (spatial > verbal). Psychological findings were consistent with an ongoing anxiety disorder. Initial diagnostic impression of ADHD and oppositional defiance was ruled-out. MNB analysis revealed a pattern of findings consistent with diffuse neuropsychological deficits relating to an inflammatory condition such as Long COVID. Memory, attention, and processing speed were below the cut-off, a finding in agreement with previous research showing impaired results, especially for memory. Because memory, as well as fatigue, seems to be affected by COVID-19, future research should explore possible interactions with cognition and fatigue following COVID-19.

Parietal resting-state EEG alpha source connectivity is associated with subcortical white matter lesions in HIV-positive people

ObjectiveParietal resting-state electroencephalographic (rsEEG) alpha (8–10 Hz) source connectivity is abnormal in HIV-positive persons. Here we tested whether this abnormality may be associated with subcortical white matter vascular lesions in the cerebral hemispheres. MethodsClinical, rsEEG, and magnetic resonance imaging (MRI) datasets in 38 HIV-positive persons and clinical and rsEEG datasets in 13 healthy controls were analyzed. Radiologists visually evaluated the subcortical white matter hyperintensities from T2-weighted FLAIR MRIs (i.e., Fazekas scale). In parallel, neurophysiologists estimated the eLORETA rsEEG source lagged linear connectivity from parietal cortical regions of interest. ResultsCompared to the HIV participants with no/negligible subcortical white matter hyperintensities, the HIV participants with mild/moderate subcortical white matter hyperintensities showed lower parietal interhemispheric rsEEG alpha lagged linear connectivity. This effect was also observed in HIV-positive persons with unimpaired cognition. This rsEEG marker allowed good discrimination (area under the receiver operating characteristic curve > 0.80) between the HIV-positive individuals with different amounts of subcortical white matter hyperintensities. ConclusionsThe parietal rsEEG alpha source connectivity is associated with subcortical white matter vascular lesions in HIV-positive persons, even without neurocognitive disorders. SignificanceThose MRI-rsEEG markers may be used to screen HIV-positive persons at risk of neurocognitive disorders.

Association of Circumscribed Subcortical Gray and White Matter Lesions With Apraxic Deficits in Patients With Left Hemisphere Stroke.

Apraxia is commonly attributed to left hemisphere (LH) lesions of the cortical fronto-temporo-parietal praxis networks or white matter lesions causing disconnections between cortical nodes. By contrast, the contribution of lesions to the subcortical gray matter, that is, basal ganglia or thalamus, to apraxic deficits remains controversial. Here, we investigate whether damage to these subcortical gray matter structures (i.e., caudate nucleus, putamen, globus pallidus, and thalamus) or the adjacent white matter tracts was associated with apraxic deficits. We identified patients with distinct subcortical lesions with and without apraxia from a large retrospective sample of subacute LH ischemic stroke patients (n = 194). To test which subcortical structures (caudate nucleus, putamen, globus pallidus, thalamus, and adjacent white matter tracts), when lesioned, contributed to apraxic deficits, we statistically compared the proportion of lesioned voxels within subcortical gray and white matter structures between the apraxic and nonapraxic patients. Of the 194 stroke patients screened, 39 (median age = 65 years, range 30-82 years; median time poststroke at the apraxia assessment = 7 days, range 1-44 days) had lesions confined to subcortical regions (gray and white matter). Eleven patients showed apraxic deficits when imitating gestures or pantomiming object use. Region-wise statistical lesion comparison (controlled for lesion size) revealed a more significant proportion of damage ('lesion load') in the caudate nucleus in apraxic stroke patients (mean difference = 6.9%, 95% CI 0.4-13.3, p = 0.038, η p 2 = 0.11). By contrast, apraxic patients had lower lesion load in the globus pallidus (mean difference = 9.9%, 95% CI 0.1-19.8, p = 0.048, η p 2 = 0.10), whereas the lesion load in other subcortical structures (putamen, thalamus, and adjacent white matter tracts) did not differ significantly between the apraxic and nonapraxic patients. These findings provide new insights into the subcortical anatomy of apraxia after LH stroke, suggesting a specific contribution of caudate nucleus lesions to apraxic deficits.

Cerebral lesions sites in neurosarcoidosis: a lesion mapping study.

Sarcoidosis is a granulomatous disease of unknown etiology affecting the central nervous system in up to 15% of the patients. Diagnosis of neurosarcoidosis is very challenging due to the heterogeneity of its clinical manifestation. This study intended to evaluate the distribution of cerebral lesion sites and the potential presence of specific lesion clusters in neurosarcoidosis patients using voxel-based lesion symptom mapping (VLSM). Patients with neurosarcoidosis were retrospectively identified and included between 2011 and 2022. Cerebral lesion sites were correlated voxel-wise with presence and absence of neurosarcoidosis using non-parametric permutation test. Multiple sclerosis patients served as controls for the VLSM-analysis. Thirty-four patients (mean age 52 ± 15years) of whom 13 were diagnosed with possible, 19 with probable and 2 with confirmed neurosarcoidosis were identified. Lesion overlap of neurosarcoidosis patients demonstrated a distribution of white matter lesions in all brain areas, with a periventricular predilection similar to multiple sclerosis. In contrast to multiple sclerosis controls, no propensity for lesions in proximity of the corpus callosum was observed. Neurosarcoidosis lesions appeared smaller and lesion volume was lower in the neurosarcoidosis cohort. The VLSM analysis showed minor associations between neurosarcoidosis and damaged voxels in the bilateral frontobasal cortex. The VLSM analysis yielded significant associations in the bilateral frontal cortex, suggesting that leptomeningeal inflammatory disease with following cortical involvement is a quite specific feature in neurosarcoidosis. Lesion load was lower in neurosarcoidosis than in multiple sclerosis. However, no specific pattern of subcortical white matter lesions in neurosarcoidosis was revealed.

Cortical Superficial Siderosis and Transient Focal Neurological Episode Preceding Lobar Hemorrhage in Cerebral Amyloid Angiopathy.

Cortical Superficial Siderosis and Transient Focal Neurological Episode Preceding Lobar Hemorrhage in Cerebral Amyloid Angiopathy.

Hepatitis B virus-induced CD4 lymphocytopenia: A rare cause of progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a rare subacute-onset fatal demyelinating disease of the central nervous system caused by the John Cunningham (JC) virus. It usually occurs in impaired cell-mediated immunity settings such as lymphoproliferative disorders, chronic infective or granulomatous conditions on immunosuppressive medications, and human immunodeficiency virus infection. It also appears very rarely with idiopathic CD4 lymphocytopenia. We present a case of PML with visual field defect, progressive motor impairment, behavioral alteration, and dementia. Magnetic resonance imaging had features of asymmetric non-enhancing hyperintense subcortical white matter lesions in the background of chronic active hepatitis B infection. To the best of our knowledge, this is the first case report of CD4 lymphocytopenia associated PML following chronic hepatitis B infection.

Rho-Kinase Inhibition Improves the Outcome of Focal Subcortical White Matter Lesions.

Subcortical white matter lesions are exceedingly common in cerebral small vessel disease and lead to significant cumulative disability without an available treatment. Here, we tested a rho-kinase inhibitor on functional recovery after focal white matter injury. A focal corpus callosum lesion was induced by stereotactic injection of N5-(1-iminoethyl)-L-ornithine in mice. Fasudil (10 mg/kg) or vehicle was administered daily for 2 weeks, starting one day after lesion induction. Resting-state functional connectivity and grid walk performance were studied longitudinally, and lesion volumes were determined at one month. Resting-state interhemispheric functional connectivity significantly recovered between days 1 and 14 in the fasudil group (P<0.001), despite worse initial connectivity loss than vehicle before treatment onset. Grid walk test revealed an increased number of foot faults in the vehicle group compared with baseline, which persisted for at least 4 weeks. In contrast, the fasudil arm did not show an increase in foot faults and had smaller lesions at 4 weeks. Immunohistochemical examination of reactive astrocytosis, synaptic density, and mature oligodendrocytes did not reveal a significant difference between treatment arms. These data show that delayed fasudil posttreatment improves functional outcomes after a focal subcortical white matter lesion in mice. Future work will aim to elucidate the mechanisms.

Brain structural alterations and clinical features of cognitive frailty in Japanese community-dwelling older adults: the Arao study (JPSC-AD)

Cognitive frailty (CF) is a clinical condition defined by the presence of both mild cognitive impairment (MCI) and physical frailty (PF). Elderly with CF are at greater risk of dementia than those with MCI or PF alone, but there are few known clinical or neuroimaging features to reliably distinguish CF from PF or MCI. We therefore conducted a population-based cross-sectional study of community elderly combining physical, cognitive, neuropsychiatric, and multisequence magnetic resonance imaging (MRI) evaluations. The MRI evaluation parameters included white matter (WM) lesion volumes, perivascular and deep subcortical WM lesion grades, lacunar infarct prevalence, microbleed number, and regional medial temporal lobe (MTL) volumes. Participants were divided into 4 groups according to the presence or absence of MCI and PF—(1) no MCI, PF (n = 27); (2) no PF, MCI (n = 119); (3) CF (MCI + PF) (n = 21), (4) normal controls (n = 716). Unique features of CF included shorter one-leg standing time; severe depressive symptoms; and MRI signs of significantly more WM lesions, lacunar infarcts, small-vessel disease lesions, microbleeds, and reduced MTL volumes. These unique deficits suggest that interventions for CF prevention and treatment should focus on motor skills, depressive symptoms, and vascular disease risk factor control.

Reactivation of latent viruses in Neurology

After establishing latent infection, some viruses can be reactivated by the alteration of host immunological conditions. First, we reviewed viruses that can cause neuronal damage by reactivation. Then we focused on the herpes simplex virus (HSV). The reactivation leads to neuronal damages through two possible mechanisms; "reactivation of a latent herpes virus" by which viruses can cause direct virus neurotoxicity, and "post-infectious immune inflammatory response" by which a focal reactivation of HSV leads to an inflammatory reaction. The former is radiologically characterized by cortical lesions, the latter is characterized by subcortical white matter lesions. We experienced a female, who underwent the right posterior quadrantectomy and then developed recurrent herpes encephalitis caused by herpes simplex reactivation, which pathologically demonstrated inflammation in the white matter, suggesting a post-infectious immune inflammatory response. The patient was successfully treated with immunosuppressants. The reactivation of the HSV is extremely rare in Japan. Neurologists should recognize this condition because this disorder will increase as epilepsy surgery gains more popularity.

Pathomechanisms of Vascular Depression in Older Adults.

Depression in older individuals is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, associated with high disability, cognitive decline, and increased mortality The factors predicting the risk of late-life depression (LLD) are incompletely understood. The reciprocal relationship of depressive disorder and age- and disease-related processes has generated pathogenic hypotheses and provided various treatment options. The heterogeneity of depression complicates research into the underlying pathogenic cascade, and factors involved in LLD considerably differ from those involved in early life depression. Evidence suggests that a variety of vascular mechanisms, in particular cerebral small vessel disease, generalized microvascular, and endothelial dysfunction, as well as metabolic risk factors, including diabetes, and inflammation that may induce subcortical white and gray matter lesions by compromising fronto–limbic and other important neuronal networks, may contribute to the development of LLD. The “vascular depression” hypothesis postulates that cerebrovascular disease or vascular risk factors can predispose, precipitate, and perpetuate geriatric depression syndromes, based on their comorbidity with cerebrovascular lesions and the frequent development of depression after stroke. Vascular burden is associated with cognitive deficits and a specific form of LLD, vascular depression, which is marked by decreased white matter integrity, executive dysfunction, functional disability, and poorer response to antidepressive therapy than major depressive disorder without vascular risk factors. Other pathogenic factors of LLD, such as neurodegeneration or neuroimmune regulatory dysmechanisms, are briefly discussed. Treatment planning should consider a modest response of LLD to antidepressants, while vascular and metabolic factors may provide promising targets for its successful prevention and treatment. However, their effectiveness needs further investigation, and intervention studies are needed to assess which interventions are appropriate and effective in clinical practice.

Electroencephalographic Findings in a Cohort of Egyptian Systemic Lupus Erythematosus Patients with Neuropsychiatric Manifestations

Abstract Background and Objective Neuropsychiatric manifestations are frequently reported in 75% of Systemic Lupus Erythematosus (SLE) patients and that varied from mild subtle signs: headache or mood disturbance to life threatening conditions: acute confusional state, major fits, stroke or transverse myelitis. Electroencephalography (EEG) was used to determine whether there is a lateralized pattern of electrophysiologic dysfunction in SLE patients or not. So, this study was done to describe EEG findings in a cohort of Egyptian SLE patients with Neuropsychiatric SLE (NPSLE), its possible correlation with any of the disease activity parameters and comparing them to patients with Non-NPSLE. Patients and Methods This case-control study was conducted on 60 SLE patients who fulfilled the 2015 ACR/SLICC Classification Criteria for SLE. They were classified into 2 groups: 30 patients with NPSLE as cases and 30 patients without NPSLE (Non-NPSLE) as controls. All patients were subjected to detailed medical history taking together with full clinical examination and calculations of SLE disease activity using the SLE disease activity index (SLEDAI) score. Laboratory investigations including CBC, ESR, CRP, BUN, creatinine, urine analysis, P/C ratio, C3, C4, Lupus Anticoagulant (LAC) and Anticardiolipin (ACL) antibodies and EEG were done for all patients. MRI brain was done for patients with NPSLE. Results There were 6 neuropsychiatric manifestations in the NPSLE group; the commonest was seizure disorders (43.3%), followed by psychosis (20.0%), cerebrovascular disease (16.7%), acute confusional state (13.3%), headache (10.0%) and lastly demyelinating syndrome (6.7%). SLEDAI score was higher in NPSLE group (Median=16) than nonNPSLE group (Median=4) (P &amp;lt; 0.01). ACL IgM positivity was higher in NPSLE group (P &amp;lt; 0.05). 53.3% of NPSLE group had abnormal MRI brain findings, the most common finding was periventricular white matter lesion (23.3%), followed by infarction (13.3%), subcortical white matter lesion and demyelinating lesion (6.7%). Lastly was sinus thrombosis, cerebral edema and encephalomalacia (3.3% each). 12 patients out of 30 (40.0%) with NPSLE had EEG abnormalities, while all 30 patients with non-NPSLE had no EEG abnormalities. The most common EEG abnormalities in NPSLE group were diffuse slowing (20.0%), followed by generalized epileptiform activity (13.3%), and lastly temporal epileptiform activity (6.7% each). 50% of patients with abnormal EEG had normal MRI. 13 patients out of 30 with NPSLE had seizure disorders (43.3%), 8 of them had abnormal EEG (61.5%). Conclusion Not all patients with NPSLE must have abnormal brain MRI or EEG. EEG is a useful assistant tool in diagnosing and studying the different manifestations of NPSLE especially seizure disorder and acute confusional state, but it cannot be used as a screening test alone for detecting NPSLE and must be supplemented by neuroimaging studies.

A patient with probable neuro‐Behçet's disease presenting a unique linear pontine trigeminal root lesion and a linear subcortical white matter lesion

AbstractBackgroundNeuro‐Behçet's disease (NBD) is typically characterized by inflammatory lesions with vasculitis in the brainstem and basal ganglia. Subcortical white matter lesions and linear lesions along the intramedullary trigeminal nerve are rare, and these lesions make NBD difficult to differentiate from other demyelinating diseases, such as multiple sclerosis.Case presentationA 48‐year‐old woman with an 11‐year history of intestinal Behçet's disease was referred to Department of Neurology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan owing to numbness on the left side of her face and oral cavity for 12 days. Neurological examination revealed left facial hypoesthesia. Brain magnetic resonance imaging showed a linearly shaped T2/fluid‐attenuated inversion recovery hyperintense magnetic resonance imaging lesion in the left pons, which corresponded neuroanatomically with the intramedullary trigeminal root. Based on the presumptive diagnosis of NBD, a course of high‐dose intravenous methylprednisolone was administered on the 14th hospital day. Thereafter, the patient's neurological symptoms improved. However, on the 18th hospital day, the patient developed a linear subcortical white matter lesion with vasogenic edema in the right hemisphere that resolved after the re‐administration of high‐dose intravenous methylprednisolone.ConclusionThe case of a patient with NBD presenting with atypical brain lesions is reported. The NBD in this case might have a pathogenetic mechanism that is different from that of typical NBD.

Magnetic resonance imaging in neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system (CNS) associated with antibodies to aquaporin-4 (AQP4), which has distinct clinical, radiological and pathological features, but also has some overlap with multiple sclerosis and myelin oligodendrocyte glycoprotein (MOG) antibody associated disease. Early recognition of NMOSD is important because of differing responses to both acute and preventive therapy. Magnetic resonance (MR) imaging has proved essential in this process. Key MR imaging clues to the diagnosis of NMOSD are longitudinally extensive lesions of the optic nerve (more than half the length) and spinal cord (three or more vertebral segments), bilateral optic nerve lesions and lesions of the optic chiasm, area postrema, floor of the IV ventricle, periaqueductal grey matter, hypothalamus and walls of the III ventricle. Other NMOSD-specific lesions are denoted by their unique morphology: heterogeneous lesions of the corpus callosum, 'cloud-like' gadolinium (Gd)-enhancing white matter lesions and 'bright spotty' lesions of the spinal cord. Other lesions described in NMOSD, including linear periventricular peri-ependymal lesions and patch subcortical white matter lesions, may be less specific. The use of advanced MR imaging techniques is yielding further useful information regarding focal degeneration of the thalamus and optic radiation in NMOSD and suggests that paramagnetic rim patterns and changes in normal appearing white matter are specific to MS. MR imaging is crucial in the early recognition of NMOSD and in directing testing for AQP4 antibodies and guiding immediate acute treatment decisions. Increasingly, MR imaging is playing a role in diagnosing seronegative cases of NMOSD.

Clinical Profile of Posterior Reversible Encephalopathy Syndrome(PRES)-Related Epilepsy in Patients Following Haploidentical Hematopoietic Stem Cell Transplantation:a 10-Year Study

AbstractIntroductionPosterior reversible encephalopathy syndrome (PRES) is a clinical-neuroradiological entity characterized by seizures, headache, altered mental status and visual disturbances associated with typical transient lesions on magnetic resonance imaging (MRI). Haploidentical hematopoietic stem cell transplant (haplo-HSCT) is an upfront and effective therapy for hematological patients, but it has a large spectrum of neurological complications including PRES. Epilepsy is a common manifestation but there is no information on epilepsy following PRES. The aim of the present study was to describe clinical characteristics and potentially unrecognized risk factors for PRES-related epilepsy following haplo-HSCT.MethodsA nested case-control study was conducted at the Institute of Hematology, Peking University People's Hospital between January 2007 and July 2017.Forty patients with PRES-related epilepsy were identified, and 122 controls were matched for transplantation type, and time of transplantation. The diagnosis of PRES was based on characteristic clinical findings and characteristic findings of subcortical white matter lesions on CT or MRI of the brain. PRES-related epilepsy was defined as at least two unprovoked seizures occurring >24 h apart more than one month after the inciting episode with complete or near complete resolution of imaging abnormalities (Fisher RS, et al. Epilepsia 2014; Sha Z,et al. Epilepsy Behav 2015; Hinduja,et al. Epilepsy Behav 2016).Additionally, patients with prior history of epilepsy were excluded. A provoked seizure was defined as a seizure that occurred in the context of a precipitating cause that could lower the seizure threshold.ResultsForty patients were defined as PRES-related epilepsy. The cumulative incidences of the disease at 100 days, 1 year and 2 years post-transplantation were 0.4%, 1.7%, 2.2%, respectively.Magnetic resonance imaging (MRI) or computed tomography(CT) was collected during 4 days of the onset of epilepsy seizures. CT was performed in 3 patients. The median time of appearance for PRES-related epilepsy was 107.1 days(rang:15-839). The mean age at the time of presentation was 18 years(range:5-47). Eleven patients had acute myeloid leukemia,12 patients had acute lymphoblastic leukemia,4 patients had chronic myelogenous leukemia,6 patients had aplastic anemia,7 patients had myelodysplastic syndrome.Thirty-two patients (80%) were diagnosed with GVHD, and 8 patients (20%) had grade Ⅲ to IV GVHD before day 100.Five patients died from disease relapse,6 patients from infection.In univariate analysis, an increased risk of PRES-related epilepsy was associated with age (<10years/³10years), mean arterial pressure (MAP), hyponatremia, hypochloremia, serum lactate dehydrogenase (LDH) and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) (³1) were related to the occurrence of PRES-related epilepsy. Multivariate analysis showed that MAP (OR= 1.053,95% CI 1.031 to 1.075,P=0.000), hyponatremia (OR=1.27,95% CI 1.139 to 1.417,P=0.000), hypochloremia (OR=0.77,95% CI 0.692 to 0.856,P=0.000) and HCT-CI (³1) (OR=9.505, 95% CI 1.262 to 71.574,P=0.027) were risk factors for PRES-related epilepsy.The median follow-up for the survivors was 1423 days (rang:95-3018).The 10-year overall survival did not significantly differ between the two groups (PRES-related epilepsy 73.2% and control 82.8%,P = 0.184).ConclusionMAP, hyponatremia, hypochloremia and HCT-CI(³1) are related with the occurrence of PRES-related epilepsy after haplo-HSCT. PRES-related epilepsy had no influence on long-term survival. DisclosuresNo relevant conflicts of interest to declare.

Focal Subcortical White Matter Lesions Disrupt Resting State Cortical Interhemispheric Functional Connectivity in Mice.

The corpus callosum is the largest white matter tract and critical for interhemispheric connectivity. Unfortunately, neurocognitive deficits after experimental white matter lesions are subtle and variable, limiting their translational utility. We examined resting state functional connectivity (RSFC) as a surrogate after a focal lesion in the lateral corpus callosum induced by stereotaxic injection of L-NIO in mice. RSFC was performed via optical intrinsic signal imaging through intact skull before and on days 1 and 14 after injection, using interhemispheric homotopic and seed-based temporal correlation maps. We measured the lesion volumes at 1 month in the same cohort. L-NIO induced focal lesions in the corpus callosum. Interhemispheric homotopic connectivity decreased by up to 50% 24 h after L-NIO, partially sparing the visual cortex. All seeds showed loss of connectivity to the contralateral hemisphere. Moreover, ipsilesional motor and visual cortices lost connectivity within the same hemisphere. Sham-operated mice did not show any lesion or connectivity changes. RSFC imaging reliably detects acute disruption of long interhemispheric and intrahemispheric connectivity after a corpus callosum lesion in mice. This noninvasive method can be a functional surrogate to complement neurocognitive testing in both therapeutic and recovery studies after white matter injury.

The Clinical, Radiologic, and Prognostic Differences Between Pediatric and Adult Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Encephalomyelitis.

Purpose: To evaluate the clinical differences between pediatric and adult patients with myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM).Methods: We retrospectively reviewed the clinical features of pediatric and adult patients with MOG-EM in our center between November 2015 and October 2020.Results: Twenty-eight pediatric patients and 25 adults were admitted to our study. Bilateral optic neuritis (BON) was the most common initial phenotype in the pediatric group but less common in the adult group (28.57 vs. 0%, p = 0.0119). Almost half of the adult patients presented with neuromyelitis optica spectrum disease (NMOSD), which was less prevalent among the pediatrics (48 vs. 21.43%, p = 0.0414). Visual impairment was the most common symptom in both groups during the initial attack (pediatric group, 39.29%; adult group, 64%) and throughout the full course (pediatric group, 57.14%; adult group, 72%). More pediatric patients suffered from fever than adult patients at onset (pediatric group, 28.57%; adult group, 4%; p = 0.0442) and throughout the full course (pediatric group, 39.29%; adult group, 12%; p = 0.0245). Multiple patchy lesions in subcortical white matter (pediatric group, 40.74%; adult group, 45%), periventricular (pediatric group, 25.93%; adult group, 35%), infratentorial (pediatric group, 18.52%; adult group, 30%) and deep gray matter (pediatric group, 25.93%; adult group, 20%) were frequent in all cases, no significant difference was found between the two groups, while bilateral optic nerve involvement was more frequent in pediatric group (61.54 vs. 14.29%, p = 0.0042) and unilateral optic nerve involvement was higher in adult group (64.29 vs. 15.38%, p = 0.0052). At the last follow-up, adult patients had a higher average EDSS score (median 1.0, range 0–3) than pediatrics (median 0.0, range 0–3), though not significant (p = 0.0752). Patients aged 0–9 years (61.54%) and 10–18 years (70%), and patients presenting with encephalitis/meningoencephalitis (100%) and ADEM (75%) were more likely to recover fully.Conclusions: Visual impairment was the dominant symptom in both pediatric and adult patients, while fever was more frequent in pediatric patients. Data suggested that BON and bilateral optic nerve involvement were more common in pediatric cases whereas NMOSD and unilateral optic nerve involvement were more prevalent in adults. The younger patients and patients presenting with encephalitis/meningoencephalitis and ADEM tended to recover better.

Moyamoya Syndrome in Post-Transplant Children with Type 1 Neurofibromatosis and Congenital Nephrotic Syndrome

Background: Neurofibromatosis (NF) is a genetic disorder of the nervous system that affects the development and growth of neuronal tissues. It is characterized by the development of malignant and benign tumors of the peripheral nerves and meningiomas, and the clinical manifestations can vary, including cerebral vascular compromise that precipitates symptoms characteristic of Moyamoya syndrome. The behavior of a posttransplant child with type 1 NF who presents with characteristics of Moyamoya syndrome and is a carrier of a WT1 genetic mutation is unknown, which is why the report was made. Case Report: A child with type I NF with a history of cryptorchidism, hypospadias, bilateral sensorineural hearing loss, and chronic renal failure was arising from a congenital nephrotic syndrome due to a WT1 gene mutation at 3 years of age began renal replacement therapy initially with chronic ambulatory peritoneal dialysis and hemodialysis for refractory peritonitis. He underwent two episodes of transient ischemic attack (TIA) characterized by right hemiparesis during hemodialysis therapy and during six months post-kidney transplantation present a similar episode. Studies for other causes were negative, and imaging studies show characteristics of NF-related vasculitis, cortical lesions, and focal lesions in the left frontal subcortical white matter with annular enhancement and subcortical edema in the parasagittal region of the left parietal lobe, as well as a decrease in flow in the cortical branches of the middle cerebral artery were described. After four weeks, the clinical manifestations of hemiparesis completely disappeared without leaving any sequels continuing with the regular immunosuppression of the everolimus, mycophenolate and low dose steroids. Conclusion: These findings are suggestive of small and mediumsized vessel vasculitis compatible with Moyamoya syndrome in child post-transplantation associated with arteriopathy by NF.