Abstract 54: Investigating Correlations Between Infarct Topography and Long-Term Outcomes Following Neonatal Arterial Ischemic Stroke Using Voxel-Based Lesion-Symptom Mapping

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mark T Mackay ◽  
Jian Chen ◽  
Joseph Yang ◽  
Belinda Stojanovski ◽  
Sebastian Grunt ◽  
...  

Objectives: To investigate correlations between infarct topography on acute diffusion weighted MRI, using voxel-based lesion-symptom mapping (VLSM), and later development of cerebral palsy (CP) and neurological impairments, in neonatal arterial ischaemic stroke (AIS). Methods: Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language or cognitive-behavioural impairments were assessed using the Pediatric Stroke Outcome Measure dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using axial DWI images, and coregistered to the Melbourne Children’s Regional Infant Brain 2.0 atlas. All lesions were projected to the left hemisphere to obtain binary union masks. VLSM was conducted using MATLAB SPM12 toolbox. A generalised linear model was used to correlate the lesion mask with outcomes. Voxel-wise t test statistics were calculated, and corrected for multiple comparisons using family-wise error rate (FWE). Results: 85 newborns (55 male) met inclusion criteria. Infarct lateralization was left hemisphere in 62%, right in 8% and bilateral in 29%. At median age 2.1 years (IQR1.9-2.6), 34% developed CP and 42% had neurological impairments. 54 ROIs were correlated with CP (t>4.33; FWE <0.05); the 12 highest correlated ROIs were the superior corona radiata, putamen, anterior corona radiata, insula, thalamus, external capsule, pars triangularis, caudate, lateral orbitofrontal cortex, superior temporal cortex, pars opercularis and precentral cortex. (Figure) No significant correlations were found for poor language or cognitive-behavioural outcomes. Conclusions: Cerebral palsy following neonatal AIS correlates predominantly with regions of acute infarction directly involved in motor control, or in functionally connected regions. Brain regions associated with language or cognitive-behavioural impairment are less clear.

Brain ◽  
2010 ◽  
Vol 133 (11) ◽  
pp. 3269-3280 ◽  
Author(s):  
Solène Kalénine ◽  
Laurel J. Buxbaum ◽  
Harry Branch Coslett

2011 ◽  
Vol 24 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Jessica D. Richardson ◽  
Julie M. Baker ◽  
Paul S. Morgan ◽  
Chris Rorden ◽  
L. Bonilha ◽  
...  

Lesion-symptom mapping studies are based upon the assumption that behavioral impairments are directly related to structural brain damage. Given what is known about the relationship between perfusion deficits and impairment in acute stroke, attributing specific behavioral impairments to localized brain damage leaves much room for speculation, as impairments could also reflect abnormal neurovascular function in brain regions that appear structurally intact on traditional CT and MRI scans. Compared to acute stroke, the understanding of cerebral perfusion in chronic stroke is far less clear. Utilizing arterial spin labeling (ASL) MRI, we examined perfusion in 17 patients with chronic left hemisphere stroke. The results revealed a decrease in left hemisphere perfusion, primarily in peri-infarct tissue. There was also a strong relationship between increased infarct size and decreased perfusion. These findings have implications for lesion-symptom mapping studies as well as research that relies on functional MRI to study chronic stroke.


2019 ◽  
Author(s):  
Cortney M. Howard ◽  
Louisa L. Smith ◽  
H. Branch Coslett ◽  
Laurel J. Buxbaum

The mechanisms and brain regions underlying error monitoring in complex action are poorly understood, yet errors and impaired error correction in these tasks are hallmarks of apraxia, a common disorder associated with left hemisphere stroke. Accounts of monitoring of language posit an internal route by which production planning or competition between candidate representations provide predictive signals that monitoring is required to prevent error, and an external route in which output is monitored using the comprehension system. Abnormal reliance on the external route has been associated with damage to brain regions critical for sensory-motor transformation and a pattern of gradual error ‘clean-up’ called conduite d’approche (CD). Action pantomime data from 67 participants with left hemisphere stroke were consistent with versions of internal route theories positing that competition signals monitoring requirements. Support Vector Regression Lesion Symptom Mapping (SVR-LSM) showed that lesions in the inferior parietal, posterior temporal, and arcuate fasciculus/superior longitudinal fasciculus predicted action conduite d’approche, overlapping the regions previously observed in the language domain. A second experiment with 12 patients who produced substantial action CD assessed whether factors impacting the internal route (action production ability, competition) versus external route (vision of produced actions, action comprehension) influenced correction attempts. In these ‘high CD’ patients, vision of produced actions and integrity of gesture comprehension interacted to determine successful error correction, supporting external route theories. Viewed together, these and other data suggest that skilled actions are monitored both by an internal route in which conflict aids in detection and correction of errors during production planning, and an external route that detects mismatches between produced actions and stored knowledge of action appearance. The parallels between language and action monitoring mechanisms and neuroanatomical networks pave the way for further exploration of common and distinct processes across these domains.


2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Christian Gerlach ◽  
Solja K Klargaard ◽  
Dag Alnæs ◽  
Knut K Kolskår ◽  
Jens Karstoft ◽  
...  

Abstract Developmental prosopagnosia is a disorder characterized by profound and lifelong difficulties with face recognition in the absence of sensory or intellectual deficits or known brain injury. While there has been a surge in research on developmental prosopagnosia over the last decade and a half, the cognitive mechanisms behind the disorder and its neural underpinnings remain elusive. Most recently it has been proposed that developmental prosopagnosia may be a manifestation of widespread disturbance in neural migration which affects both face responsive brain regions as well as other category-sensitive visual areas. We present a combined behavioural and functional MRI study of face, object and word processing in a group of developmental prosopagnosics (N = 15). We show that developmental prosopagnosia is associated with reduced activation of core ventral face areas during perception of faces. The reductions were bilateral but tended to be more pronounced in the left hemisphere. As the first study to address category selectivity for word processing in developmental prosopagnosia, we do not, however, find evidence for reduced activation of the visual word form area during perception of orthographic material. We also find no evidence for reduced activation of the lateral occipital complex during perception of objects. These imaging findings correspond well with the behavioural performance of the developmental prosopagnosics, who show severe impairment for faces but normal reading and recognition of line drawings. Our findings suggest that a general deficit in neural migration across ventral occipito-temporal cortex is not a viable explanation for developmental prosopagnosia. The finding of left hemisphere involvement in our group of developmental prosopagnosics was at first surprising. However, a closer look at existing studies shows similar, but hitherto undiscussed, findings. These left hemisphere abnormalities seen in developmental prosopagnosia contrasts with lesion and imaging studies suggesting primarily right hemisphere involvement in acquired prosopagnosia, and this may reflect that the left hemisphere is important for the development of a normal face recognition network.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 488
Author(s):  
Milda Sarkinaite ◽  
Rymante Gleizniene ◽  
Virginija Adomaitiene ◽  
Kristina Dambrauskiene ◽  
Nijole Raskauskiene ◽  
...  

Structural brain changes are found in suicide attempters and in patients with mental disorders. It remains unclear whether the suicidal behaviors are related to atrophy of brain regions and how the morphology of specific brain areas is changing with each suicide attempt. The sample consisted of 56 patients hospitalized after first suicide attempt (first SA) (n = 29), more than one suicide attempt (SA > 1) (n = 27) and 54 healthy controls (HC). Brain volume was measured using FreeSurfer 6.0 automatic segmentation technique. In comparison to HC, patients with first SA had significantly lower cortical thickness of the superior and rostral middle frontal areas, the inferior, middle and superior temporal areas of the left hemisphere and superior frontal area of the right hemisphere. In comparison to HC, patients after SA > 1 had a significantly lower cortical thickness in ten areas of frontal cortex of the left hemisphere and seven areas of the right hemisphere. The comparison of hippocampus volume showed a significantly lower mean volume of left and right parts in patients with SA > 1, but not in patients with first SA. The atrophy of frontal, temporal cortex and hippocampus parts was significantly higher in repeated suicide attempters than in patients with first suicide attempt.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander A. Aabedi ◽  
Sofia Kakaizada ◽  
Jacob S. Young ◽  
Jasleen Kaur ◽  
Olivia Wiese ◽  
...  

AbstractLexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Few studies have probed lexical retrieval with tasks other than picture naming, and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent results emerged. The presence of a single construct for auditory and visual processes of lexical retrieval would influence cognitive rehabilitation strategies for patients with aphasia. In this study, we perform support vector regression lesion-symptom mapping using a brain tumor model to test the hypothesis that brain regions specifically involved in lexical retrieval from visual and auditory stimuli represent overlapping neural systems. We find that principal components analysis of language tasks revealed multicollinearity between picture naming, auditory naming, and a validated measure of word finding, implying the existence of redundant cognitive constructs. Nonparametric, multivariate lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral prefrontal cortex (PFC) were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC.


Author(s):  
Maria Gladkikh ◽  
Hugh J. McMillan ◽  
Andrea Andrade ◽  
Cyrus Boelman ◽  
Ishvinder Bhathal ◽  
...  

ABSTRACT: Background: Childhood acute arterial ischemic stroke (AIS) is diagnosed at a median of 23 hours post-symptom onset, delaying treatment. Pediatric stroke pathways can expedite diagnosis. Our goal was to understand the similarities and differences between Canadian pediatric stroke protocols with the aim of optimizing AIS management. Methods: We contacted neurologists at all 16 Canadian pediatric hospitals regarding AIS management. Established protocols were analyzed for similarities and differences in eight domains. Results: Response rate was 100%. Seven (44%) centers have an established AIS protocol and two (13%) have a protocol under development. Seven centers do not have a protocol; two redirect patients to adult neurology, five rely on a case-by-case approach for management. Analysis of the seven protocols revealed differences in: 1) IV-tPA dosage: age-dependent 0.75–0.9 mg/kg (N = 1) versus age-independent 0.9 mg/kg (N = 6), with maximum doses of 75 mg (N = 1) or 90 mg (N = 6); 2) IV-tPA lower age cut-off: 2 years (N = 5) versus 3 or 10 years (each N = 1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (N = 3), <5 (N = 1), <6 (N = 3); 4) first choice of pre-treatment neuroimaging: computed tomography (CT) (N = 3), magnetic resonance imaging (MRI) (N = 2) or either (N = 2); 5) intra-arterial tPA use (N = 3) and; 6) mechanical thrombectomy timeframe: <6 hour (N = 3), <24 hour (N = 2), unspecified (N = 2). Conclusions: Although 44% of Canadian pediatric hospitals have established AIS management pathways, several differences remain among centers. Some criteria (dosage, imaging) reflect adult AIS literature. Canadian expert consensus regarding IV-tPA and endovascular treatment should be established to standardize and implement AIS protocols across Canada.


2021 ◽  
Author(s):  
Fabienne Kühne ◽  
Alexander Jungbluth ◽  
Joanna Schneider ◽  
Christoph Bührer ◽  
Christine Prager ◽  
...  

Purpose: Perinatal ischemic stroke (PIS) is a frequent cause for perinatal brain structure defects resulting in epilepsy, cerebral palsy and disability. Since the severity of symptoms is variable, the aim of this study was to evaluate the outcome of children with PIS and seizures/epilepsy to aid parental counseling and therapy decisions. Material: We studied retrospectively patients with arterial PIS and structural epilepsy or seizures in the newborn treated at a single center in 2000-2019. Specifically, signs and symptoms of cerebral palsy (CP), developmental and motor delay, epilepsy and thrombophilia were assessed. Results: From the identified 69 individuals with arterial PIS, we only included the 50 patients (64% male) who had structural epilepsy at the time of investigation or previously in their medical history.The mean age of the included patients was 7.1 years (range 0.08-22) at last consultation. Infarct localisation was predominantly unilateral (86%), left sided (58%) and affecting the middle cerebral artery (94%). Genetic thrombophilia was identified in 52% of the patients examined with genetic testing. More than half of the individuals had CP (52%), and 38.5% had a cognitive outcome below average. First seizures occurred in the neonatal period in 58% of patients and developed into drug-refractory epilepsy in 24.1%. Children with late-onset of epilepsy were twice as likely to develop drug-refractory epilepsy (52.4%). Discussion: Our study shows that patients with PIS and seizures as common sequela often also develop CP. Children with later onset of epilepsy have a worse outcome. Patients with seizure onset in the neonatal period and reccuring seizures have a good response to treatment. Therefore, early diagnosis, follow-up examination and adequate therapy are important. Most children need intensive physiotherapy and speech therapy; however, participation in life is usually age-appropriate.


2021 ◽  
Author(s):  
Rahat Hasan ◽  
Jack Humphrey ◽  
Conceicao Bettencourt ◽  
Tammaryn Lashley ◽  
Pietro Fratta ◽  
...  

Frontotemporal lobar degeneration (FTLD) is a group of heterogeneous neurodegenerative disorders affecting the frontal and temporal lobes of the brain. Nuclear loss and cytoplasmic aggregation of the RNA-binding protein TDP-43 represents the major FTLD pathology, known as FTLD-TDP. To date, there is no effective treatment for FTLD-TDP due to an incomplete understanding of the molecular mechanisms underlying disease development. Here we compared post-mortem tissue RNA-seq transcriptomes from the frontal cortex, temporal cortex and cerebellum between 28 controls and 30 FTLD-TDP patients to profile changes in cell-type composition, gene expression and transcript usage. We observed downregulation of neuronal markers in all three regions of the brain, accompanied by upregulation of microglia, astrocytes, and oligodendrocytes, as well as endothelial cells and pericytes, suggesting shifts in both immune activation and within the vasculature. We validate our estimates of neuronal loss using neuropathological atrophy scores and show that neuronal loss in the cortex can be mainly attributed to excitatory neurons, and that increases in microglial and endothelial cell expression are highly correlated with neuronal loss. All our analyses identified a strong involvement of the cerebellum in the neurodegenerative process of FTLD-TDP. Altogether, our data provides a detailed landscape of gene expression alterations to help unravel relevant disease mechanisms in FTLD.


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