Aju plastilisus ja võrgustike reorganiseerumine perinataalset insulti põdenud lastel: funktsionaalne magnetresonantstomograafiline uuring

Väitekirja elektrooniline versioon ei sisalda publikatsiooneViimastel aastakümnetel on arstide, aga ka elanikkonna teadlikkus tõusnud, et insult võib esineda kogu elu jooksul, ka lastel. Eriti suur insuldi tõenäosus on vastsündinueas, umbes üks tuhande elussünni kohta. Insult vastsündinueas võib kaasa tuua elukestva motoorse, kognitiivse kahjustuse ning epilepsia, lisanduda võivad käitumishäired ja sotsiaalne puue. Vastsündinuea insult mõjutab väga pika aja jooksul lisaks lastele ka nende lähedasi, tuues kaasa stressi ja depressiooni kogu perele, ning koormab majanduslikult tervet ühiskonda. Vastsündinuea insuldi järgne ajukahjustus on olenevalt tekkemehhanismist ja suurusest erinev, ka laste areng ja oskused on sellest tulenevalt erinevad. Õnneks on laste aju arenev ja plastiline ning suudab vähemalt osa ajukahjustustest võrreldes täiskasvanutega paremini kompenseerida. Kuna insult on harvaesinev ja kahjustus varieeruv, on teadmised vastsündinuea insuldi kohta piiratud. Uurimistöö eesmärk oli uurida vastsündinuea insuldiga laste aju võimet võrreldes tervete lastega kahjustust erinevate kahjustuse tüüpide ja ulatuste puhul kompenseerida. Me kasutasime erinevaid magnetresonantstomograafilisi (MRT) uuringuid koos pilditöötlusega, et leida tunnuseid, mille abil oleks võimalik juba esimestel eluaastatel ennustada insuldiga laste kognitiivseid ja motoorseid võimeid ja paremini planeerida taastusravi. Uuringu tulemused näitasid vastsündinuea insuldiga laste motoorsete ja kognitiivsete võimete ning aju ümberorganiseerumise seost kahjustuse ulatuse ja tüübiga. Muutused insuldiga vastsündinu ajus aitavad kompenseerida ja vähendada kahjustuse mõju, kuid ei suuda täielikult tagada eakohast arengut. Uuringus saadud teadmisi aju plastilisuse ja ümberorganiseerumisvõime kohta on võimalik rakendada lisaks insuldihaigetele ka teiste ajukahjustusega (nt trauma, ajukasvaja või epilepsia) laste puhul. Need teadmised täiendavad vastsündinuea insuldi laste radioloogilistest uuringutest saadavat teavet, rõhutades nende vajalikkust.Stroke can occur during the entire lifetime and is probably underdiagnosed in children. In perinatal period the risk of stroke is especially high, about 1:1000 live births. Perinatal stroke may lead to various motor and cognitive impairments and epilepsy. Perinatal stroke causes lifelong physical, mental and emotional disabilities and social burden not only to children, but also to their families along with an economic burden to the society. Perinatal stroke is a heterogonous condition, with different brain lesions depending on the vascular type of stroke leading to different outcomes. Children’s brain is plastic and able to reorganize and at least partly compensate for damage after stroke. However, the knowledge of perinatal stroke is still limited due to the low prevalence and inherent heterogeneity of damage. The aim of the study was to investigate brain’s ability to reorganize in different vascular types of perinatal stroke compared to healthy controls and to evaluate how it affects the motor, cognitive and language outcomes. Various radiological markers for predicting motor, cognitive and language outcome in children with perinatal stroke were identified using functional magnetic resonance imaging and volumetric image analysis. The study showed that motor, cognitive and language outcomes in children with perinatal stroke correlates with vascular type and extent of stroke lesion. The brain’s plasticity and reorganization abilities were shown to only minimize the negative effect of large stroke lesions, but not to ensure entirely normal outcome. The knowledge of brain plasticity and reorganization in perinatal stroke children can be generalized to cases involving other focal brain damages, like trauma, tumors and epilepsy. The study accentuates the importance of radiological investigation of children with perinatal stroke and enhances the value of radiological evaluation.https://www.ester.ee/record=b551935

Ipsilesional volume loss of basal ganglia and thalamus is associated with poor hand function after ischemic perinatal stroke

Background Perinatal stroke (PS) is the leading cause of hemiparetic cerebral palsy (CP). Involvement of the corticospinal tract on neonatal magnetic resonance imaging (MRI) is predictive of motor outcome in patients with hemiparetic CP. However, early MRI is not available in patients with delayed presentation of PS and prediction of hemiparesis severity remains a challenge. Aims To evaluate the volumes of the basal ganglia, amygdala, thalamus, and hippocampus following perinatal ischemic stroke in relation to hand motor function in children with a history of PS and to compare the volumes of subcortical structures in children with PS and in healthy controls. Methods Term born PS children with arterial ischemic stroke (AIS) (n = 16) and with periventricular venous infarction (PVI) (n = 18) were recruited from the Estonian Pediatric Stroke Database. MRI was accuired during childhood (4-18 years) and the volumes of the basal ganglia, thalamus, amygdala and hippocampus were calculated. The results of stroke patients were compared to the results of 42 age- and sex-matched healthy controls. Affected hand function was evaluated by Assisting Hand Assessment (AHA) and classified by the Manual Ability Classification System (MACS). Results Compared to the control group, children with AIS had smaller volumes of the ipsi- and contralesional thalami, ipsilesional globus pallidus, nucleus accumbens and hippocampus (p 0.5; p < 0.05) and larger volume of the contralesional putamen and hippocampus (r < - 0.5; p < 0.05). In children with PVI, size of the ipsilesional caudate nucleus, globus pallidus, thalamus (p 0.55; p < 0.05) in children with PVI. Conclusions Smaller volume of ipsilesional thalamus was associated with poor affected hand function regardless of the perinatal stroke subtype. The pattern of correlation between hand function and volume differences in the other subcortical structures varied between children with PVI and AIS. Evaluation of subcortical structures is important in predicting motor outcome following perinatal stroke.Peer reviewe

Kõnekeskuse lateralisatsioon ja kaugtulemused erineva vaskulaarse alatüübiga perinataalse insuldiga lastel

Eesti Arst 2022; 101(12):71

General ability and specific cognitive functions are lower in children with epilepsy after perinatal ischemic stroke

IntroductionEpilepsy develops in one third of children after perinatal stroke. Both epilepsy and stroke may be risk factors for impaired cognitive abilities. How the development of epilepsy is related to the cognitive profile of children with perinatal stroke is still unclear. The aim of the study was to evaluate general and specific cognitive functions in children with epilepsy and children without epilepsy after perinatal ischemic stroke.MethodsThe study group consisted of 51 children with perinatal ischemic stroke confirmed by magnetic resonance imaging: 27 (53%) children with arterial ischemic stroke and 24 (47%) with periventricular venous infarction. Magnetic resonance imaging and electroencephalography were performed in all patients after the neonatal period. Epilepsy was diagnosed if the child had at least two unprovoked seizures occurring &gt;24 h apart or one unprovoked seizure with a high recurrence risk. Cognitive assessments were performed using the Kaufman Assessment Battery for Children, Second Edition, at the age of ≥7 years. General ability (Fluid Crystallized Index, Mental Processing Index, Non-verbal Index) and specific cognitive functions (sequential processing, simultaneous processing, learning, planning, knowledge) were evaluated.ResultsAt the median age of 19.3 years (interquartile range 14.0–22) at the time of follow-up for epilepsy, 14 (27.5%) patients had developed epilepsy, and 37 (72.5%) patients were without epilepsy. All general cognitive ability scores were lower in children with epilepsy compared to children without epilepsy. Among specific cognitive functions, simultaneous processing, planning, and knowledge were lower in children with epilepsy compared to children without epilepsy: simultaneous processing mean [78.5, 95% CI: [69.8, 87.2], vs. 96.9, 95% CI [90, 103.9], p = 0.0018]; planning mean [82.5, 95% CI: [73, 92], vs. 96.2, 95% CI: [88.7, 103.6], p = 0.026]; knowledge median (25th, 75th percentile): 80.5 (75, 87) vs. 92 (84, 108), p = 0.023.ConclusionChildren with epilepsy after perinatal ischemic stroke have lower general cognitive abilities compared to children without epilepsy. The profile of the subscales indicates lower verbal abilities and executive functions in children with epilepsy. Children with post-stroke epilepsy need targeted cognitive monitoring for early aimed rehabilitation and for establishing an adapted learning environment

Magnetresonantstomograafiaga seotud riskid ja ohutuse tagamine

Magnetresonantstomograafia (MRT) on nüüdisaegne radioloogiline uurimismeetod, mis võimaldab kompuutertomograafiaga (KT) võrreldes paremini hinnata keha eri piirkondade pehmete kudede seisundit. Erinevalt KT- ja röntgenuuringutest ei kasutata MRTs patsienti kahjustavat ioniseerivat röntgenikiirgust. Kujutis patsiendi uuritavast piirkonnast luuakse mitteioniseeriva elektromagnetkiirguse abil. MRT-uuringute arv on aastate jooksul järjest suurenenud, kuna uurigu näidustusi on erialadel aina rohkem. Kui 2009. aastal tehti Tartu Ülikooli Kliinikumis MRT-uuringuid ca 6000 patsiendile, siis nüüdseks on see arv kasvanud 12 000-ni. Peale uuritavate arvu suurenemise on aja jooksul lisandunud üha keerulisemaid uuringuid (näiteks kardioloogia ja neuroloogia vallas), mida 10 aasta eest peaaegu ei tehtud ning mille tegemiseks kulub rohkem aega. Arvestades järjest suurenevat MRT-uuringute arvu, on oluline tähelepanu pöörata MRT-uuringuga kaasnevatele riskidele

Resting-State Functional Connectivity and Cognitive Impairment in Children with Perinatal Stroke

Perinatal stroke is a leading cause of congenital hemiparesis and neurocognitive deficits in children. Dysfunctions in the largescale resting-state functional networks may underlie cognitive and behavioral disability in these children. We studied resting-state functional connectivity in patients with perinatal stroke collected from the Estonian Pediatric Stroke Database. Neurodevelopment of children was assessed by the Pediatric Stroke Outcome Measurement and the Kaufman Assessment Battery. The study included 36 children (age range 7.6-17.9 years): 10 with periventricular venous infarction (PVI), 7 with arterial ischemic stroke (AIS), and 19 controls. There were no differences in severity of hemiparesis between the PVI and AIS groups. A significant increase in default mode network connectivity (FDR 0.1) and lower cognitive functions (p <0.05) were found in children with AIS compared to the controls and the PVI group. The children with PVI had no significant differences in the resting-state networks compared to the controls and their cognitive functions were normal. Our findings demonstrate impairment in cognitive functions and neural network profile in hemiparetic children with AIS compared to children with PVI and controls. Changes in the resting-state networks found in children with AIS could possibly serve as the underlying derangements of cognitive brain functions in these children.Peer reviewe

Grey matter abnormalities in methcathinone abusers with a Parkinsonian syndrome

Funding Information: The study was supported by Grants GARNR9199 and GARLA0148P of the Estonian Science Foundation, and Grant No. 5.8.2 of the National Research Program of Latvia. Ricarda A L Menke is employed by the University of Oxford and her salary is funded by the Medical Research Council of the UK. Heidi Johansen-Berg is employed by the Universities of Oxford and Oslo, holds grants from the Wellcome Trust, National Institutes of Health Research, Education Endowment Foundation, Stroke Association, and Royalties from Elsevier. Charlotte J Stagg holds a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society. Ain?rs Stepens holds Grant No. 5.8.2 of the National Research Program of Latvia, which supported this study. Pille Taba holds Grant 9199 of the Estonian Science Foundation, which supported this study, is principal investigator of Grant 3.2.1001.11-0017 of the EU European Regional Development Fund, and participates in Grant IUT2-4 of the Estonian Research Council. Publisher Copyright: © 2016 The Authors. Brain and Behavior published by Wiley Periodicals, Inc. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.Background: A permanent Parkinsonian syndrome occurs in intravenous abusers of the designer psychostimulant methcathinone (ephedrone). It is attributed to deposition of contaminant manganese, as reflected by characteristic globus pallidus hyperintensity on T1-weighted MRI. Methods: We have investigated brain structure and function in methcathinone abusers (n = 12) compared to matched control subjects (n = 12) using T1-weighted structural and resting-state functional MRI. Results: Segmentation analysis revealed significant (p <.05) subcortical grey matter atrophy in methcathinone abusers within putamen and thalamus bilaterally, and the left caudate nucleus. The volume of the caudate nuclei correlated inversely with duration of methcathinone abuse. Voxel-based morphometry showed patients to have significant grey matter loss (p <.05) bilaterally in the putamina and caudate nucleus. Surface-based analysis demonstrated nine clusters of cerebral cortical thinning in methcathinone abusers, with relative sparing of prefrontal, parieto-occipital, and temporal regions. Resting-state functional MRI analysis showed increased functional connectivity within the motor network of patients (p <.05), particularly within the right primary motor cortex. Conclusion: Taken together, these results suggest that the manganese exposure associated with prolonged methcathinone abuse results in widespread structural and functional changes affecting both subcortical and cortical grey matter and their connections. Underlying the distinctive movement disorder caused by methcathinone abuse, there is a more widespread pattern of brain involvement than is evident from the hyperintensity restricted to the basal ganglia as shown by T1-weighted structural MRI.Peer reviewe

Image_3_The thalamus and basal ganglia are smaller in children with epilepsy after perinatal stroke.pdf

BackgroundEpilepsy is one of the most serious consequences of perinatal stroke. Epilepsy itself has been proposed as a risk factor for impaired cognitive, language, and behavioral functioning. It is still unclear which children develop epilepsy after perinatal stroke. The current study aimed to evaluate the volume of the thalamus and the basal ganglia in children after perinatal stroke in relation to poststroke epilepsy.MethodsThe follow-up study included 29 children with perinatal arterial ischemic stroke (AIS), 33 children with presumed periventricular venous infarction (PVI), and 46 age- and sex-matched healthy controls. Magnetic resonance imaging was performed in children between the ages of 4 and 18 years, and volumetric analysis by segmentation was used to evaluate the size of the thalamus, caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens.ResultsDuring a median follow-up time of 12.8 years [interquartile range (IQR): 10.8–17.3] in the AIS group and 12.5 years (IQR: 9.3–14.8) in the PVI group (p = 0.32), epilepsy developed in 10 children (34.5%) with AIS and in 4 (12.1%) children with PVI, p = 0.036 [odds ratio (OR) = 3.8, 95%, confidence interval (CI): 1.04–14]. Epilepsy and interictal epileptiform discharges (IEDs) without clinical seizures were more often expressed in children with AIS (n = 16, 55%) than in children with PVI (n = 7, 21.2%), p = 0.0057 (OR = 3.8 95% CI: 1.04–14). In the AIS group, the ipsilesional and contralesional thalamus, ipsilesional caudate nucleus, and nucleus accumbens were significantly smaller in children with epilepsy compared to children without epilepsy. In the PVI group, the ipsilesional thalamus, caudate nucleus, and nucleus accumbens were smaller in the pooled group of epilepsy plus IED alone compared to children without epilepsy.ConclusionIn children with AIS, epilepsy or IED occurred more often compared to children with PVI. Both patients with AIS and PVI with severe damage to the basal ganglia and the thalamus have a higher risk of developing poststroke epilepsy and should be monitored more closely throughout childhood to initiate timely antiseizure medication and rehabilitation.</p

Image_1_The thalamus and basal ganglia are smaller in children with epilepsy after perinatal stroke.pdf

BackgroundEpilepsy is one of the most serious consequences of perinatal stroke. Epilepsy itself has been proposed as a risk factor for impaired cognitive, language, and behavioral functioning. It is still unclear which children develop epilepsy after perinatal stroke. The current study aimed to evaluate the volume of the thalamus and the basal ganglia in children after perinatal stroke in relation to poststroke epilepsy.MethodsThe follow-up study included 29 children with perinatal arterial ischemic stroke (AIS), 33 children with presumed periventricular venous infarction (PVI), and 46 age- and sex-matched healthy controls. Magnetic resonance imaging was performed in children between the ages of 4 and 18 years, and volumetric analysis by segmentation was used to evaluate the size of the thalamus, caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens.ResultsDuring a median follow-up time of 12.8 years [interquartile range (IQR): 10.8–17.3] in the AIS group and 12.5 years (IQR: 9.3–14.8) in the PVI group (p = 0.32), epilepsy developed in 10 children (34.5%) with AIS and in 4 (12.1%) children with PVI, p = 0.036 [odds ratio (OR) = 3.8, 95%, confidence interval (CI): 1.04–14]. Epilepsy and interictal epileptiform discharges (IEDs) without clinical seizures were more often expressed in children with AIS (n = 16, 55%) than in children with PVI (n = 7, 21.2%), p = 0.0057 (OR = 3.8 95% CI: 1.04–14). In the AIS group, the ipsilesional and contralesional thalamus, ipsilesional caudate nucleus, and nucleus accumbens were significantly smaller in children with epilepsy compared to children without epilepsy. In the PVI group, the ipsilesional thalamus, caudate nucleus, and nucleus accumbens were smaller in the pooled group of epilepsy plus IED alone compared to children without epilepsy.ConclusionIn children with AIS, epilepsy or IED occurred more often compared to children with PVI. Both patients with AIS and PVI with severe damage to the basal ganglia and the thalamus have a higher risk of developing poststroke epilepsy and should be monitored more closely throughout childhood to initiate timely antiseizure medication and rehabilitation.</p

Image_4_The thalamus and basal ganglia are smaller in children with epilepsy after perinatal stroke.pdf

BackgroundEpilepsy is one of the most serious consequences of perinatal stroke. Epilepsy itself has been proposed as a risk factor for impaired cognitive, language, and behavioral functioning. It is still unclear which children develop epilepsy after perinatal stroke. The current study aimed to evaluate the volume of the thalamus and the basal ganglia in children after perinatal stroke in relation to poststroke epilepsy.MethodsThe follow-up study included 29 children with perinatal arterial ischemic stroke (AIS), 33 children with presumed periventricular venous infarction (PVI), and 46 age- and sex-matched healthy controls. Magnetic resonance imaging was performed in children between the ages of 4 and 18 years, and volumetric analysis by segmentation was used to evaluate the size of the thalamus, caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens.ResultsDuring a median follow-up time of 12.8 years [interquartile range (IQR): 10.8–17.3] in the AIS group and 12.5 years (IQR: 9.3–14.8) in the PVI group (p = 0.32), epilepsy developed in 10 children (34.5%) with AIS and in 4 (12.1%) children with PVI, p = 0.036 [odds ratio (OR) = 3.8, 95%, confidence interval (CI): 1.04–14]. Epilepsy and interictal epileptiform discharges (IEDs) without clinical seizures were more often expressed in children with AIS (n = 16, 55%) than in children with PVI (n = 7, 21.2%), p = 0.0057 (OR = 3.8 95% CI: 1.04–14). In the AIS group, the ipsilesional and contralesional thalamus, ipsilesional caudate nucleus, and nucleus accumbens were significantly smaller in children with epilepsy compared to children without epilepsy. In the PVI group, the ipsilesional thalamus, caudate nucleus, and nucleus accumbens were smaller in the pooled group of epilepsy plus IED alone compared to children without epilepsy.ConclusionIn children with AIS, epilepsy or IED occurred more often compared to children with PVI. Both patients with AIS and PVI with severe damage to the basal ganglia and the thalamus have a higher risk of developing poststroke epilepsy and should be monitored more closely throughout childhood to initiate timely antiseizure medication and rehabilitation.</p