Neuroimaging Patterns Research Articles

Functional connectivity in Parkinson\u2019s disease candidates for deep brain stimulation

This study aimed to identify functional neuroimaging patterns anticipating the clinical indication for deep brain stimulation (DBS) in patients with Parkinson’s disease (PD). A cohort of prospectively recruited patients with PD underwent neurological evaluations and resting-state functional MRI (RS-fMRI) at baseline and annually for 4 years. Patients were divided into two groups: 19 patients eligible for DBS over the follow-up and 41 patients who did not meet the criteria to undergo DBS. Patients selected as candidates for DBS did not undergo surgery at this stage. Sixty age- and sex-matched healthy controls performed baseline evaluations. Graph analysis and connectomics assessed global and local topological network properties and regional functional connectivity at baseline and at each time point. At baseline, network analysis showed a higher mean nodal strength, local efficiency, and clustering coefficient of the occipital areas in candidates for DBS over time relative to controls and patients not eligible for DBS. The occipital hyperconnectivity pattern was confirmed by regional analysis. At baseline, a decreased functional connectivity between basal ganglia and sensorimotor/frontal networks was found in candidates for DBS compared to patients not eligible for surgery. In the longitudinal analysis, patient candidate for DBS showed a progressively decreased topological brain organization and functional connectivity, mainly in the posterior brain networks, and a progressively increased connectivity of basal ganglia network compared to non-candidates for DBS. RS-fMRI may support the clinical indication to DBS and could be useful in predicting which patients would be eligible for DBS in the earlier stages of PD.

Headache neuroimaging: A survey of current practice, barriers, and facilitators to optimal use.

The objective of this study was to understand current practice, clinician understanding, attitudes, barriers, and facilitators to optimal headache neuroimaging practices. Headaches are common in adults, and neuroimaging for these patients is common, costly, and increasing. Although guidelines recommend against routine headache neuroimaging in low-risk scenarios, guideline-discordant neuroimaging is still frequently performed. We administered a 60-item survey to headache clinicians at the Veterans Affairs health system to assess clinician understanding and attitudes on headache neuroimaging and to determine neuroimaging practice patterns for three scenarios describing hypothetical patients with headaches. Descriptive statistics were used to summarize responses, stratified by clinician type (physicians or advanced practice clinicians [APCs]) and specialty (neurology or primary care). The survey was successfully completed by 431 of 1426 clinicians (30.2% response rate). Overall, 317 of 429 (73.9%) believed neuroimaging was overused for patients with headaches. However, clinicians would utilize neuroimaging a mean (SD) 30.9% (31.7) of the time in a low-risk scenario without red flags, and a mean 67.1% (31.9) of the time in the presence of minor red flags. Clinicians had stronger beliefs in the potential benefits (268/429, 62.5%) of neuroimaging compared to harms (181/429, 42.2%) and more clinicians were bothered by harms stemming from the omission of neuroimaging (377/426, 88.5%) compared to commission (329/424, 77.6%). Additionally, APCs utilized neuroimaging more frequently than physicians and were more receptive to potential interventions to improve neuroimaging utilization. Although a majority of clinicians believed neuroimaging was overused for patients with headaches, many would utilize neuroimaging in low-risk scenarios with a small probability of changing management. Future studies are needed to define the role of currently used red flags given their importance in neuroimaging decisions. Importantly, APCs may be an ideal target for future optimization efforts.

Clinical features of mental disorders in amyotrophic lateral sclerosis

To investigate the clinical features of associated mental disorders in amyotrophic lateral sclerosis (ALS). Twenty-seven patients (9 men and 18 women, mean age 59.8±11.9 years) with the upper and lower motor neuron lesions were studied. The average duration of the disease at the time of examination was 3.2±2.4 years. Clinical psychopathological and follow-up methods were used. The severity of cognitive impairment was measured with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess the severity of depression. Most patients (88.9%) had cognitive impairments. Amnestic disorders were primarily presented by hypo- and dysmnesia. These patients showed slow thinking, torpidity combined with circumstantiality and a tendency to detail. In addition to attentional fluctuations, we observed reduced attentional capacity, higher distractibility, and difficulty concentrating. The later stages of the disease were accompanied by the overall decline of thinking ability and intelligence with severe perseverations, and failure in the adequate self-assessment. More than half of the patients also developed the symptoms, such as dynamic aphasia, as well as functional speech disorders, i.e. gnosis and praxis. The vast majority of the patients had affective disorders (92.3%). So far as the symptoms of the underlying neurological condition worsened, the associated depressive symptoms prevailed (62.9%). Particular attention should be given to the clinical cases of ALS associated with psychotic disorders such as acute schizophrenia-like psychotic disorders. Presence of affective, cognitive and behavioral disorders, as well as a specific neuroimaging pattern, are considered as a whole as the manifestation of the behavioral variant of frontotemporal dementia (FTD). This provides support for the current opinion suggesting the similarity of ALS and FTD, which allows for considering these diseases as different phenotypic manifestations of a single pathological process.

Anti-Tr/DNER Antibody–Associated Cerebellar Ataxia: a Systematic Review

Rapidly progressive cerebellar ataxia is a classical paraneoplastic neurological syndrome associated with different autoantibodies and typical demographic characteristics, extracerebellar signs, tumor association, and prognosis. Anti-Tr/anti-Delta/Notch-like epidermal growth factor-related receptor (DNER) antibody is one of the associated antibodies. Given the rarity of this condition, our current knowledge is based on case reports and small case series. In order to improve our understanding of these conditions, we conducted a systematic review of the literature. Our study followed the PRISMA reporting guidelines. Studies of patients with the presence of anti-Tr/DNER antibodies in serum or cerebrospinal fluid (CSF) were included. We extract data information related to study characteristics, demographics, clinical symptoms, tumor association, neuroimaging, and cerebrospinal fluid analysis. Out of 131 records, we analyzed 17 papers, including a total of 85 patients with anti-Tr/DNER antibody-associated cerebellar ataxia. We confirmed that this disease occurred mostly in middle-aged males. Isolated cerebellar ataxia was the most common presentation. Extracerebellar features were rare (8%). Ninety-one percent of the patients presented an associated tumor, being Hodgkin lymphoma the most common. Abnormal neuroimaging patterns included cerebellar atrophy (19%) and cerebellar hypersignal (6%). Cerebrospinal fluid was inflammatory in 64% of the patients. Oncological response was complete in 88%, but neurological prognosis was poor with only 41% of the patients presenting significant neurological improvement at the last follow up. Anti-Tr/DNER antibodies should be tested in rapid progressive cerebellar ataxia. Oncological response is excellent; however, many patients do not improve from their cerebellar ataxia.

VARIATIONS IN CLINICAL PRESENTATION, NEUROIMAGING AND EEG PATTERNS OF SUBACUTE SCLEROSING PANENCEPHALITIS

Objective: To determine the variations in clinical presentation, neuroimaging and electroencephalography patterns of subacute sclerosing panencephalitis.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Children’s Hospital & Institute of Child Health, Lahore, Pakistan, from Jul to Dec 2020.
 Methodology: We recruited children presented with clinical features suggestive of subacute sclerosing panencephalitis, along with positive anti-measles antibodies on cerebrospinal fluid. Association between variables was determined to formulate an early diagnosis of subacute sclerosing panencephalitis.
 Results: Out of 47 children, 29 were males with a mean age of 6.54 ± 2.9 years. Only 23% were fully immunized against measles, 36.2% were unvaccinated and 40.4% received partial immunization. The mean age of measles infection was 1.49 ± 1.2 years; the mean interval between measles and onset of SSPE was 4.13 ± 3 years. Atypical clinical presentation was seen in 38.3% with intractable epilepsy (8.5%), focal deficit (8.5%) and extrapyramidal symptoms (8.5%) being commonest followed by coma (6.4%), visual loss (4.3%) and psychosis (2.1%). Neuroimaging was suggestive of cortical hyperintensities in 46.8% and was normal in 46.8%. Electroencephalography showed burst suppression in 55.3% and atypical findings in 19.1%. Younger age (1-1.5 years) of measles and unimmunized status were associated with early onset of SSPE with a p-value of 0.001 and 0.05 respectively. Non-immunized status was associated with atypical presentation of SSPE (p-value <0.05).
 Conclusion: The younger age of measles infection and failure to receive complete immunization led to early onset of Subacute sclerosing panencephalitis with an atypical presentation.

Osteopontin in patients with metabolic syndrome and cognitive impairment

Metabolic syndrome is associated with dysmetabolic and proinflammatory pathophysiological mechanisms, which lead to cognitive impairment. Evaluation of the effect of osteopontin as a predictor of these changes with the analysis of the neuroimaging pattern of the brain is of interest.Purpose of the study: analysis of the role of osteopontin in patients with metabolic syndrome in the formation of cognitive impairment.Material and Methods: the study complies with generally accepted ethical rules and included 50 patients with type metabolic syndrome (which were divided into groups according to cognitive impairment) and 25 control groups. All underwent a general clinical examination, blood sampling for biochemical parameters, including osteopontin. Magnetic resonance imaging (MRI) was performed on a Signa Creator "E" magnetic resonance tomograph, GE Healthcare, 1.5 Tesla, China: techniques were dynamic contrast and arterial spin labels, proton spectroscopy, tractography. SPSS Statistic program was used for statistical analysis.Results: osteopontin was higher in patients with overweight, hyperglycemia, hyperuricemia, dyslipidemia, and cognitive impairment, and in the neuroimaging study with microangiopathy according to perfusion MRI, impaired integration of the white matter of the brain, as well as neurometabolism in the hippocampal region by choline, creatine and phosphocreatine metabolites in the hippocampal region, as well as their NAA/Cr, NAA/Cho, Cho/Cr ratios (p≤0.05).Conclusion: patients with metabolic syndrome and cognitive disorders revealed elevated levels of osteopontin, which is also associated with impaired cerebral vascularization in general and white matter organization, as well as neurometabolism in the hippocampus..

Distinctive Neuroimaging Pattern in Term Newborns With Neonatal Placental Encephalopathy: A Case Series

BackgroundIdentifying antepartum versus intrapartum timing and the cause of neonatal encephalopathy (NE) often remains elusive owing to our limited understanding of the underlying pathophysiological processes and lack of appropriate biomarkers. ObjectivesThis retrospective observational study describes a case series of term newborns with NE who displayed a recognizable magnetic resonance imaging pattern of immediately postnatal brain abnormalities that rapidly evolved toward cavitation. Our aim is to (1) report this neuroimaging pattern, (2) look for placental determinants, and (3) depict the outcome. Design/MethodsThis is a unicentric retrospective case series reporting the clinical, radiological, and laboratory findings of NE associated with a distinctive neuroimaging pattern, that is, immediately postnatal extensive corticosubcortical T2 hyperintensities, followed by rapid corticosubcortical cavitation that does not match the neuroimaging picture of intrapartum hypoxic-ischemic encephalopathy (HIE). ResultsSeven term newborns presented bilateral corticosubcortical hyperintensities that were detected on T2 between day of life (DOL) 1-4, which rapidly evolved toward cystic encephalomalacia, that is, between DOL9 and DOL12. All these newborns presented with moderate/severe NE. The outcome was either neonatal death or quadriplegic cerebral palsy and epilepsy. None of the reported patients fulfilled the criteria of a high likelihood of acute intrapartum hypoxic-ischemic or quadriplegic cerebral palsy. All these newborns were exposed to chronic and/or acute placental inflammation and/or hypoxic-ischemic. ConclusionsTo further define the antepartum causes of NE, early neuroimaging and a placental examination are recommended. Brain T2 hyperintense injuries before DOL4 followed by rapid cavitation before DOL12 might be biomarkers of NE from an antepartum/placental origin.

Two Different Neuroimaging Patterns in Two Cases with Eclampsia, HELLP syndrome and Posterior Reversible Encephalopathy Syndrome

Introduction: Preeclampsia (PE) and eclampsia are two clinical conditions associated with pregnancy. In eclampsia, seizures also occur. One of the complications of eclampsia is HELLP syndrome, a condition characterized by hemolytic anemia, elevated liver enzymes and thrombocytopenia. Preeclampsia and eclampsia are both well-known risk factors for posterior reversible encephalopathy syndrome (PRES), a clinical-radiological syndrome characterized by variable combinations of neurological signs. In this syndrome, typical neuroimaging findings are bilateral symmetric hemispheric edema in parietooccipital regions. However, atypical imaging findings have also been described. Here, we report two different neuroimaging patterns in two cases with PRES associated with eclampsia and HELLP syndrome. Case: Two pregnant female patients were admitted to our emergency department because of respiratory and neurological symptoms. While the medical history of one of the patients was unremarkable, the other patient was diagnosed with epilepsy and hypertension before pregnancy. Both of them had resistant increased blood pressure and seizures. They underwent urgent caesarean section. In the postoperative period, they were transferred into intensive care unit, necessitating mechanical ventilation because of respiratory failure. Laboratory findings were suggestive of eclampsia and HELLP syndrome and brain imaging findings were suggestive of PRES. Additionally, brain computed tomography scan of one of the patients showed subarachnoid haemorrhage and the magnetic resonance imaging scans of the other patient showed restricted diffusion, indicating cytotoxic edema. The patients were treated with blood transfusions and antihypertensive drugs. Maintenance of normotension resulted in neurological improvement. Subsequently, both of the patients were discharged without neurological sequela. Discussion and Conclusion: In this article, we reported both the associations between HELLP syndrome, eclampsia and PRES, and two different neuroimaging patterns of PRES. Effective controlling of blood pressure and treatment of HELLP syndrome resulted in complete disappearance of the radiological findings and improvement in the neurological sings.

Altered Resting-State Functional Connectivity in the Default Mode Network in Male Juvenile Violent Offenders

Young males are often associated with more violence, leading to some serious negative consequences. However, the physiology and the neuroimaging patterns underlying juvenile violence remain unclear. Of the limited knowledge on juvenile violence, the default mode network has been known to be associated with its pathophysiology. This study aimed to investigate functional connectivity alterations of the default mode network in male juvenile violent offenders. 31 juvenile violent offenders in a high-security facility, who were convicted of aggressive behaviors by court, and 28 normal controls from a middle school were recruited as participants. They underwent a resting-state functional magnetic resonance imaging scan. And independent component analysis approaches were used to analyze their data. Compared to the normal controls, the juvenile violent offenders showed a different default mode network pattern, with the functional connectivity increased in the posterior cingulate, and decreased in the right middle temporal, left angular, right precuneus and right middle frontal cortex. Our findings revealed that the male juvenile violent offenders were associated with abnormal default mode network functional connectivity, which might be a neuroimaging basis for their tendency to violence.

Whole-brain morphological alterations associated with trigeminal neuralgia

BackgroundNovel neuroimaging strategies have the potential to offer new insights into the mechanistic basis for trigeminal neuralgia (TN). The present study aims to conduct whole-brain morphometry analyses of TN patients and to assess the value of group-level neocortical and subcortical structural patterns as tools for diagnostic biomarker exploration.MethodsCortical thickness, surface area, and myelin levels in the neocortex were measured via magnetic resonance imaging (MRI). The radial distance and the Jacobian determinant of the subcortex in 43 TN patients and 43 matched controls were compared. Pattern learning algorithms were employed to establish the utility of group-level MRI findings as tools for predicting TN. An additional 40 control patients with hemifacial spasms were then evaluated to assess algorithm sensitivity and specificity.ResultsTN patients exhibited reductions in cortical indices in the anterior cingulate cortex (ACC), the midcingulate cortex (MCC), and the posterior cingulate cortex (PCC) relative to controls. They further presented with widespread subcortical volume reduction that was most evident in the putamen, the thalamus, the accumbens, the pallidum, and the hippocampus. Whole brain-level morphological alterations successfully enable automated TN diagnosis with high specificity (TN: 95.35 %; disease controls: 46.51 %).ConclusionsTN is associated with a distinctive whole-brain structural neuroimaging pattern, underscoring the value of machine learning as an approach to differentiating between morphological phenotypes, ultimately revealing the full spectrum of this disease and highlighting relevant diagnostic biomarkers.

Neuroimaging findings in children with cerebral palsy with autism and/or attention‐deficit/hyperactivity disorder: a population‐based study

To compare neuroimaging patterns according to the Magnetic Resonance Imaging Classification System (MRICS) in children with cerebral palsy (CP) with and without autism and/or attention-deficit/hyperactivity disorder (ADHD). This population-based study assessed 184 children (97 males, 87 females) with CP born from 1999 to 2006 from the CP register of western Sweden, who had completed comprehensive screening and clinical assessment for neuropsychiatric disorders and undergone neuroimaging. Autism (total prevalence 30%) and ADHD (31%) were common in all neuroimaging patterns, including normal. Autism and ADHD were not more prevalent in children with bilateral than unilateral lesions, contrary to other associated impairments. Children with predominant white matter injury, related to insults in the late second or early third trimester, had the highest prevalence of autism (40%). Children who had sustained a middle cerebral artery infarction had the highest prevalence of ADHD (62%). Although autism and ADHD are common regardless of neuroimaging patterns, timing and localization of insult appear to be of importance for the occurrence of autism and ADHD in children with CP. Neuroimaging may be of prognostic value for these associated impairments. Further in-depth neuroimaging studies may lead to a better understanding of the association between CP and neuropsychiatric disorders.

Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features

The PIDDosome is a multiprotein complex, composed by the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 that induces apoptosis in response to DNA damage. In the recent years, biallelic pathogenic variants in CRADD have been associated with a neurodevelopmental disorder (MRT34; MIM 614499) characterized by pachygyria with a predominant anterior gradient, megalencephaly, epilepsy and intellectual disability. More recently, biallelic pathogenic variants in PIDD1 have been described in a few families with apparently nonsydnromic intellectual disability. Here, we aim to delineate the genetic and radio-clinical features of PIDD1-related disorder. Exome sequencing was carried out in six consanguineous families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals as well as reviewing all the data from previously reported cases. We identified five distinct novel homozygous variants (c.2584C>T p.(Arg862Trp), c.1340G>A p.(Trp447*), c.2116_2120del p.(Val706Hisfs*30), c.1564_1565delCA p.(Gln522fs*44), and c.1804_1805del p.(Gly602fs*26) in eleven subjects displaying intellectual disability, behaviorial and psychiatric features, and a typical anterior-predominant pachygyria, remarkably resembling the CRADD-related neuroimaging pattern. In summary, we outlin`e the phenotypic and molecular spectrum of PIDD1 biallelic variants supporting the evidence that the PIDD1/CRADD/caspase-2 signaling is crucial for normal gyration of the developing human neocortex as well as cognition and behavior.

Prospective Association between Dysmenorrhea and Chronic Pain Development in Community-Dwelling Women

Despite emerging evidence of associations between dysmenorrhea, enhanced pain sensitivity, and functional neuroimaging patterns consistent with chronic pain, it is unknown whether dysmenorrhea is prospectively associated with chronic pain development. Gaining a better understanding of this relationship could inform efforts in prevention of chronic pain. Using data from the national Midlife in the United States cohort, we examined the prospective association between dysmenorrhea and chronic pain development during a 10-year follow-up (starting 10 years after dysmenorrhea was measured) among 874 community-dwelling women aged 25-74 at baseline (when dysmenorrhea was measured). We fit modified Poisson regression models adjusting for sociodemographic, lifestyle and psychosocial factors. Among women who were menstruating at baseline, self-reported dysmenorrhea was associated with a 41% greater (95% confidence interval [CI] = 6%-88%) risk of developing chronic pain. Women with dysmenorrhea also developed chronic pain in more body regions (≥3 regions vs 1-2 regions vs none, odds ratio [OR] = 1.77, 95% CI = 1.18-2.64) and experienced greater pain interference (high-interference vs low-interference vs none, OR = 1.73, 95% CI = 1.15-2.59). Among women who had stopped menstruation at baseline, we did not find evidence of an association between their history of dysmenorrhea and subsequent risk of chronic pain development. Results suggest dysmenorrhea may be a general risk factor for chronic pain development among menstruating women. PerspectiveThis study supports the temporality of dysmenorrhea and chronic pain development in a national female sample. Dysmenorrhea was also associated with developing more widespread and disabling pain among women who were still menstruating. Early management of dysmenorrhea may reduce the development and severity of chronic pain in women, although further research is required to determine whether dysmenorrhea is a causal risk factor or a risk marker of chronic pain.

Abstract P89: Covid-19 and Ischemic Stroke: A Systematic Review and Meta-Summary of the Literature

Background: Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. Objectives: We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. Methods: A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. Results: A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean D-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). Conclusion: We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated D-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis.

Abstract P302: Neuroimaging Embolic Infarct Pattern in Work-Up For Embolic Source of Undetermined Etiology in Acute Ischemic Stroke

Introduction: Embolic infarct pattern on Neuroimaging as a marker for positive cardioembolism results in the work-up for Embolic Source of Undetermined Etiology (ESUS) in acute ischemic stroke (AIS) is unclear. Methods: Among 1625 acute ischemic stroke (AIS) hospitalized at our academic stroke program from July 2017 to April 2019, 350 (21.5%) had complete ESUS work-up performed (defined as including TEE and cardiac monitoring). Data was abstracted on demographics, medical history, initial National Institutes of Health Stroke Scale (NIHSS), systolic blood pressure (SBP), troponin level, neuroimaging findings, and cardiac test results. Positive ESUS work-up for cardioembolism was defined as results that prompted management change. Embolic infarct pattern was defined as infarct confirmed on neuroimaging to affect 2 or more vessel territories. Results: Among 350 with complete ESUS work-up performed, the mean age was 59.0 (range, 23 to 88) and 170 (48.6%) were female. The mean initial NIHSS was 5.4 (range, 0 to 32). Neuroimaging infarct pattern suggested embolic pattern in 75 (21.4%), single vessel pattern in 274 (78.3%), and not visible in 1 (0.3%). Among 274 with single vessel infarct pattern on neuroimaging, affected territory was MCA in 184, Vertebrobasilar in 46, PCA in 34, and ACA in 10. Cardioembolism source was identified in 96 (27.4%) of patients with completed ESUS work-up (7.1% had positive findings on TEE and 20.3% had new-atrial fibrillation diagnosed on cardiac monitoring). Compared to patients with single territory infarct pattern, patients with embolic pattern were more likely to have a history of diabetes mellitus (44.0% vs 31.3%, p 0.0392), higher SBP (159.0 vs 147.9mm Hg, p 0.002) and higher troponin (0.87 vs 0.07 ng/mL, p 0.0124), but there was no significant difference based upon age, sex, history of hypertension, initial NIHSS, HgbA1c, LDL, or rate of positive ESUS work up for cardioembolism (22.7% vs 28.5%, p 0.0088). Conclusion: Among AIS patients with complete ESUS work-up, the most common neuroimaging pattern was single territory MCA infarct (52.6%) followed by embolic infarct pattern (21.4%). Embolic pattern did not increase the positive yield of ESUS work-up for cardioembolism.

Identification of Biomarkers in Patients with Thrombotic Thrombocytopenic Purpura Presenting with Large and Small Ischemic Stroke

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder resulting in organ damage including ischemic strokes. We sought to characterize the neuroimaging patterns of stroke in a large cohort of patients with immune-mediated TTP (iTTP) and determined their associations with clinical and laboratory parameters and outcomes. Methods: We analyzed the Alabama TTP Registry who had laboratory confirmation of acute iTTP. We reviewed the neuroimaging patterns of those with ischemic stroke on MRI, clinical information, and laboratory results. Small ischemic strokes were ≤20 mm in their maximum diameter in the axial plane. Large ischemic strokes were >20 mm. Student t test, Mann-Whitney U test, and χ² test were all used for data analysis. Results: Of 108 iTTP patients, 21 had ischemic stroke on neuroimaging. The median platelet count in these patients was 12 × 10⁹/L (interquartile range, IQR, 8.8–21 × 10⁹/L), plasma ADAMTS13 activity 1.8 U/dL (IQR 0–4.5 U/dL), and the mean plasma level of anti-ADAMTS13 IgG was 6,595.8 U/mL (SD 3,448.9 U/mL). Comparison between patients with large ischemic strokes (n = 10) and small ischemic strokes (n = 11) revealed that patients with small stroke were older (p = 0.043) and had higher plasma levels of citrullinated histone 3 (p = 0.006) and histone/DNA complex (p = 0.014) than those with large strokes. There were no significant differences between 2 stroke groups in mortality or exacerbation. Conclusions: iTTP patients can present with large ischemic strokes and are usually younger. Further research should be performed in assessing different etiologies of iTTP-associated stroke based on neutrophil extracellular trap formation biomarkers (e.g., histone markers) seen in small ischemic stroke.

Subpial Hemorrhage in Neonates: What Radiologists Need to Know.

OBJECTIVE. Subpial hemorrhages, typically seen in neonates, are rare but can harm the adjacent brain parenchyma. The purpose of this review is to summarize the anatomy and pathophysiology of subpial hemorrhage and highlight its characteristic neuro-imaging pattern. CONCLUSION. The distinctive neuroimaging pattern of subpial hemorrhage is best appreciated on brain MRI, which shows the morphology over the cortex and injury to adjacent cortex and subcortical white matter. These findings do not occur in subarachnoid and subdural hemorrhages. Recognizing the pattern of subpial hemorrhages should guide prognostic precision, prognostication, and counseling.

Neuroimaging Patterns and Function in Cerebral Palsy-Application of an MRI Classification.

Background: Cerebral palsy (CP) is a disorder of movement and posture and every child with CP has a unique composition of neurological symptoms, motor severity, and associated impairments, constituting the functional profile. Although not part of the CP definition, magnetic resonance imaging (MRI) sheds light on the localization, nature, and severity of brain compromise. The MRI classification system (MRICS), developed by the Surveillance of Cerebral Palsy in Europe (SCPE), describes typical MRI patterns associated with specific timing of vulnerability in different areas of the brain. The classification has proven to be reliable and easy to use.Aims: The aim of this study is to apply the MRICS on a large dataset and describe the functional profile associated with the different MRI patterns of the MRICS.Materials and Methods: Data on children with CP born in 1999–2009 with a post-neonatal MRI from 20 European registers in the JRC-SCPE Central Registry was included. The CP classification and the MRICS was applied, and The Gross Motor Function Classification (GMFCS) and the Bimanual Fine Motor Function (BFMF) classification were used. The following associated impairments were documented: intellectual impairment, active epilepsy, visual impairment, and hearing impairment. An impairment index was used to characterize severity of impairment load.Results: The study included 3,818 children with post-neonatal MRI. Distribution of CP type, motor, and associated impairments differed by neuroimaging patterns. Functional profiles associated with neuroimaging patterns were described, and the impairment index showed that bilateral findings were associated with a more severe outcome both regarding motor impairment and associated impairments than unilateral compromise. The results from this study, particularly the differences in functional severity regarding uni- and bilateral brain compromise, may support counseling and service planning of support of children with CP.

Diagnostic Approach to Cerebellar Hypoplasia.

Cerebellar hypoplasia (CH) refers to a cerebellum of reduced volume with preserved shape. CH is associated with a broad heterogeneity in neuroradiologic features, etiologies, clinical characteristics, and neurodevelopmental outcomes, challenging physicians evaluating children with CH. Traditionally, neuroimaging has been a key tool to categorize CH based on the pattern of cerebellar involvement (e.g., hypoplasia of cerebellar vermis only vs. hypoplasia of both the vermis and cerebellar hemispheres) and the presence of associated brainstem and cerebral anomalies. With the advances in genetic technologies of the recent decade, many novel CH genes have been identified, and consequently, a constant updating of the literature and revision of the classification of cerebellar malformations are needed. Here, we review the current literature on CH. We propose a systematic approach to recognize specific neuroimaging patterns associated with CH, based on whether the CH is isolated or associated with posterior cerebrospinal fluid anomalies, specific brainstem or cerebellar malformations, brainstem hypoplasia with or without cortical migration anomalies, or dysplasia. The CH radiologic pattern and clinical assessment will allow the clinician to guide his investigations and genetic testing, give a more precise diagnosis, screen for associated comorbidities, and improve prognostication of associated neurodevelopmental outcomes.

Pediatric demyelinating disease and anti‐MOG antibody

AbstractSignificant progress has been made in the field of pediatric neuroimmunology over the past few years. With the detection of conformationally correct myelin oligodendrocyte glycoprotein (MOG) antibodies using cell‐based assays, children with different monophasic and relapsing phenotypes have been increasingly described. However, there is still controversy regarding the severity of the disease course and outcome of this emerging and rapidly expanding spectrum of MOG‐associated demyelination. Accumulating evidence seems to identify MOG‐IgG–associated disorder as a disease entity different from multiple sclerosis and aquaporin 4 (AQP4)‐IgG–positive neuromyelitis optica spectrum disorder. This review will summarize recent findings regarding the spectrum of MOG‐associated disorders in pediatric patients related to diagnosis, clinical presentation, and neuroimaging patterns, including data on current available and emerging treatment options for children.