Thalamic diaschisis following perinatal stroke is associated with clinical disability

Abstract

BackgroundPerinatal stroke causes most hemiparetic cerebral palsy and leads to lifelong disability. Understanding developmental neuroplasticity following early stroke is increasingly translated into novel therapies. Diaschisis refers to alterations brain structures remote from, but connected to, stroke lesions. Ipsilesional thalamic diaschisis has been described following adult stroke but has not been investigated in perinatal stroke. We hypothesized that thalamic diaschisis occurs in perinatal stroke and its degree would be inversely correlated with clinical motor function.MethodsPopulation-based, controlled cohort study. Participants were children (<19 years) with unilateral perinatal stroke (arterial ischemic stroke [AIS] or periventricular venous infarction [PVI]), anatomical magnetic resonance imaging (MRI) >6 months of age, symptomatic hemiparetic cerebral palsy, and no additional neurologic disorders. Typically developing controls had comparable age and gender proportions. T1-weighted anatomical scans were parcellated into 99 regions of interest followed by generation of regional volumes. The primary outcome was thalamic volume expressed as ipsilesional (ILTV), contralesional (CLTV) and thalamic ratio (CLTV/ILTV). Standardized clinical motor assessments were correlated with thalamic volume metrics.ResultsFifty-nine participants (12.9 years old ±4.0 years, 46% female) included 20 AIS, 11 PVI, and 28 controls. ILTV was reduced in both AIS and PVI compared to controls (p < .001, p = .029, respectively). Ipsilesional thalamic diaschisis was not associated with clinical motor function. However, CLTV was significantly larger in AIS compared to both controls and PVI (p = .005, p < .001, respectively). CLTV was inversely correlated with all four clinical motor assessments (all p < .003).ConclusionBilateral thalamic volume changes occur after perinatal stroke. Ipsilesional volume loss is not associated with clinical motor function. Contralesional volume is inversely correlated with clinical motor function, suggesting the thalamus is involved in the known developmental plasticity that occurs in the contralesional hemisphere after early unilateral injury.

A connectome‐based approach to assess motor outcome after neonatal arterial ischemic stroke

“…The importance of the thalamus in predicting hand motor function has been already discussed many times 63,64 . These results indicate that the thalamus connections with other motor regions are directly linked to the motor score as it was demonstrated recently by 65 …”

A Connectome-Based Approach to Assess Motor Outcome after Neonatal Arterial Ischemic Stroke

“…The importance of the thalamus in predicting hand motor function has been already discussed many times 47,48 . These results indicate that the thalamus connections with other motor regions is directly linked to motor score as it was demonstrated recently by 49 .…”

Structural and functional connectivity of motor circuits after perinatal stroke: A machine learning study

“…These different patterns may be due to the relatively larger lesion size in AIS encompassing both subcortical and cortical areas compared to PVI in which injury is more constrained to the periventricular white matter. It is interesting to note that while basal ganglia structures are typically remote from PVI damage, there were still detectible differences in connectivity between these areas compared to peers perhaps mediating motor dysfunction via diaschisis, a process previously investigated in perinatal stroke patients ( Finger et al, 2004 , Kirton et al, 2016b , Craig et al, 2019a , Craig et al, 2019b , Srivastava et al, 2019 ). Also of note is the finding that values for some features found to be predictive of motor function in the regression analyses were not different from peers.…”

“…The thalamus is also a central hub for integrating sensory inputs shunting information to specialized cortical areas for further processing via significant projections to the basal ganglia and cortex via cortico-basal ganglia-thalamo-cortical loops ( Lanciego et al, 2012 ). We have recently demonstrated that thalamic diaschisis is common in perinatal stroke ( Srivastava et al, 2019 ) and that altered thalamic volumes, particularly in the non-lesioned hemisphere, are associated with motor function ( Craig et al, 2019a ). Our findings here appear consistent with this previous evidence supporting an important role for the basal ganglia and thalamus in the developmental plasticity that determines motor function after perinatal stroke.…”