The Impact of Intraventricular Hemorrhage and Periventricular Leukomalacia on Mortality and Neurodevelopmental Outcome in Very Preterm and Very Low Birthweight Infants: A Prospective Population-based Cohort Study.

OBJECTIVE: To survey the incidence of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) by gestational age and to report the impact on mortality and neurodevelopmental outcome in very preterm/very low birthweight infants. STUDY DESIGN: This was a population-based cohort study of 1927 very preterm/very low birthweight infants born in 2014-2016 and admitted to Flemish neonatal intensive care units. Infants underwent standard follow-up assessment until 2 years corrected age with the Bayley Scales of Infant and Toddler Development and neurological assessments. RESULTS: No brain lesion was present in 31% of infants born at <26 weeks of gestation and 75.8% in infants born at 29-32 weeks of gestation. The prevalence of low-grade IVH/PVL (grades I and II) was 16.8% and 12.7%, respectively. Low-grade IVH/PVL was not related significantly to an increased likelihood of mortality, motor delay, or cognitive delay, except for PVL grade II, which was associated with a 4-fold increase in developing cerebral palsy (OR, 4.1; 95% CI, 1.2-14.6). High-grade lesions (III-IV) were present in 22.0% of the infants born at <26 weeks of gestational and 3.1% at 29-32 weeks of gestation, and the odds of death were ≥14.0 (IVH: OR, 14.0; 95% CI, 9.0-21.9; PVL: OR, 14.1; 95% CI, 6.6-29.9). PVL grades III-IV showed an increased odds of 17.2 for motor delay and 12.3 for cerebral palsy, but were not found to be associated significantly with cognitive delay (OR, 2.9; 95% CI, 0.5-17.5; P = .24). CONCLUSIONS: Both the prevalence and severity of IVH/PVL decreased significantly with advancing gestational age. More than 75% of all infants with low grades of IVH/PVL showed normal motor and cognitive outcome at 2 years corrected age. High-grade PVL/IVH has become less common and is associated with adverse outcomes.

Associations Between Sensorimotor Impairments in the Upper Limb at 1 Week and 6 Months After Stroke.

BACKGROUND AND PURPOSE: Longitudinal information regarding the prevalence of upper limb somatosensory deficits and the association with motor impairment and activity limitations is scarce. The aim of this prospective cohort study was to map the extent and distribution of somatosensory deficits, and to determine associations over time between somatosensory deficits and motor impairment and activity limitations. METHODS: We recruited 32 participants who were assessed 4 to 7 days after stroke, and reassessed at 6 months. Somatosensory measurements included the Erasmus-modified Nottingham sensory assessment (Em-NSA), perceptual threshold of touch, thumb finding test, 2-point discrimination, and stereognosis subscale of the NSA. Evaluation of motor impairment comprised the Fugl-Meyer assessment, Motricity Index, and Action Research Arm Test. In addition, at 6 months, activity limitation was determined using the adult assisting hand assessment stroke, the ABILHAND, and hand subscale of the Stroke Impact Scale. RESULTS: Somatosensory impairments were common, with 41% to 63% experiencing a deficit in one of the modalities within the first week and 3% to 50% at 6 months. In the acute phase, there were only very low associations between somatosensory and motor impairments (r = 0.03-0.20), whereas at 6 months, low to moderate associations (r = 0.32-0.69) were found for perceptual threshold of touch, thumb finding test, and stereognosis with motor impairment and activity limitations. Low associations (r = 0.01-0.29) were found between somatosensory impairments in the acute phase and motor impairments and activity limitations at 6 months. DISCUSSION AND CONCLUSIONS: This study showed that somatosensory impairments are common and suggests that the association with upper limb motor and functional performance increases with time after stroke.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A138).

Validity of a sensorimotor adaptation of the Action Research Arm Test (sARAT) in chronic stroke.

PURPOSE: After stroke, upper limb somatosensation can be impaired which affects motor control. Vision is often used to compensate for this. A clinical assessment which assesses the combined sensorimotor function in the absence of vision would be beneficial in studies targeting sensorimotor improvement. METHODS AND MATERIALS: We adapted the Action Research Arm Test (ARAT) to be performed without vision and called this modified version the sensorimotor ARAT (sARAT). Sixty healthy participants and 22 participants with chronic stroke performed the ARAT, sARAT, Fugl-Meyer upper extremity assessment (FM-UE) and Erasmus modified Nottingham sensory assessment (EmNSA). Discriminative validity of sARAT was evaluated by comparing performance between healthy participants and participants with chronic stroke. Convergent validity was evaluated by correlating sARAT with FM-UE and EmNSA. RESULTS: Participants with stroke performed worse on the sARAT compared to healthy participants (p < 0.001), with median scores of 52 (IQR 32-57) and 57 (IQR 57-57), respectively. The sARAT showed high correlations with FM-UE and EmNSA (r = 0.80-0.90). CONCLUSIONS: The sARAT shows good discriminative and convergent validity in people with chronic stroke. It allows a quick assessment of the combined upper limb sensorimotor function, by performing the well-known ARAT with the eyes closed.

The sensorimotor adaptation of the Action Research Arm Test (sARAT) is a clinical assessment of upper limb activity which is performed with the eyes closed.Combining the gold standard ARAT with the sensorimotor adaptation sARAT can inform about the influence of somatosensory impairments on upper limb activity in stroke survivors when vision is blocked.The sARAT shows good discriminative and convergent validity in persons with chronic stroke.

Intensive Therapy of the Lower Limbs and the Trunk in Children with Bilateral Spastic Cerebral Palsy: Comparing a Qualitative Functional and a Functional Approach.

Few studies have examined the effect of intensive therapy on gross motor function and trunk control in children with cerebral palsy (CP). This study evaluated the effects of an intensive burst of therapy on the lower limbs and trunk by comparing qualitative functional and functional approaches. This study was designed as a quasi-randomized, controlled, and evaluator-blinded trial. Thirty-six children with bilateral spastic CP (mean age = 8 y 9 mo; Gross Motor Function Classification II and III) were randomized into functional (n = 12) and qualitative functional (n = 24) groups. The main outcome measures were the Gross Motor Function Measure (GMFM), the Quality Function Measure (QFM), and the Trunk Control Measurement Scale (TCMS). The results revealed significant time-by-approach interaction effects for all QFM attributes and the GMFM's standing dimension and total score. Post hoc tests showed immediate post-intervention gains with the qualitative functional approach for all QFM attributes, the GMFM's standing and walking/running/jumping dimension and total score, and the total TCMS score. The qualitative functional approach shows promising results with improvements in movement quality and gross motor function.

Multimodal and multidomain lesion network mapping enhances prediction of sensorimotor behavior in stroke patients.

Beyond the characteristics of a brain lesion, such as its etiology, size or location, lesion network mapping (LNM) has shown that similar symptoms after a lesion reflects similar dis-connectivity patterns, thereby linking symptoms to brain networks. Here, we extend LNM by using a multimodal strategy, combining functional and structural networks from 1000 healthy participants in the Human Connectome Project. We apply multimodal LNM to a cohort of 54 stroke patients with the aim of predicting sensorimotor behavior, as assessed through a combination of motor and sensory tests. Results are two-fold. First, multimodal LNM reveals that the functional modality contributes more than the structural one in the prediction of sensorimotor behavior. Second, when looking at each modality individually, the performance of the structural networks strongly depended on whether sensorimotor performance was corrected for lesion size, thereby eliminating the effect that larger lesions generally produce more severe sensorimotor impairment. In contrast, functional networks provided similar performance regardless of whether or not the effect of lesion size was removed. Overall, these results support the extension of LNM to its multimodal form, highlighting the synergistic and additive nature of different types of network modalities, and their corresponding influence on behavioral performance after brain injury.

Brain connectivity alterations after additional sensorimotor or motor therapy for the upper limb in the early-phase post stroke: a randomized controlled trial.

Somatosensory function plays an important role for upper limb motor learning. However, knowledge about underlying mechanisms of sensorimotor therapy is lacking. We aim to investigate differences in therapy-induced resting-state functional connectivity changes between additional sensorimotor compared with motor therapy in the early-phase post stroke. Thirty first-stroke patients with a sensorimotor impairment were included for an assessor-blinded multi-centre randomized controlled trial within 8 weeks post stroke [13 (43%) females; mean age: 67 ± 13 years; mean time post stroke: 43 ± 13 days]. Patients were randomly assigned to additional sensorimotor (n = 18) or motor (n = 12) therapy, receiving 16 h of additional therapy within 4 weeks. Sensorimotor evaluations and resting-state functional magnetic resonance imaging were performed at baseline (T1), post-intervention (T2) and after 4 weeks follow-up (T3). Resting-state functional magnetic resonance imaging was also performed in an age-matched healthy control group (n = 19) to identify patterns of aberrant connectivity in stroke patients between hemispheres, or within ipsilesional and contralesional hemispheres. Mixed model analysis investigated session and treatment effects between stroke therapy groups. Non-parametric partial correlations were used to investigate brain-behaviour associations with age and frame-wise displacement as nuisance regressors. Connections within the contralesional hemisphere that showed hypo-connectivity in subacute stroke patients (compared with healthy controls) showed a trend towards a more pronounced pre-to-post normalization (less hypo-connectivity) in the motor therapy group, compared with the sensorimotor therapy group (mean estimated difference = -0.155 ± 0.061; P = 0.02). Further, the motor therapy group also tended to show a further pre-to-post increase in functional connectivity strength among connections that already showed hyper-connectivity in the stroke patients at baseline versus healthy controls (mean estimated difference = -0.144 ± 0.072; P = 0.06). Notably, these observed increases in hyper-connectivity of the contralesional hemisphere were positively associated with improvements in functional activity (r = 0.48), providing indications that these patterns of hyper-connectivity are compensatory in nature. The sensorimotor and motor therapy group showed no significant differences in terms of pre-to-post changes in inter-hemispheric connectivity or ipsilesional intrahemispheric connectivity. While effects are only tentative within this preliminary sample, results suggest a possible stronger normalization of hypo-connectivity and a stronger pre-to-post increase in compensatory hyper-connectivity of the contralesional hemisphere after motor therapy compared with sensorimotor therapy. Future studies with larger patient samples are however recommended to confirm these trend-based preliminary findings.

Sensorimotor vs. Motor Upper Limb Therapy for Patients With Motor and Somatosensory Deficits: A Randomized Controlled Trial in the Early Rehabilitation Phase After Stroke.

Background: Somatosensory function plays an important role in motor learning. More than half of the stroke patients have somatosensory impairments in the upper limb, which could hamper recovery. Question: Is sensorimotor upper limb (UL) therapy of more benefit for motor and somatosensory outcome than motor therapy? Design: Randomized assessor- blinded multicenter controlled trial with block randomization stratified for neglect, severity of motor impairment, and type of stroke. Participants: 40 first-ever stroke patients with UL sensorimotor impairments admitted to the rehabilitation center. Intervention: Both groups received 16 h of additional therapy over 4 weeks consisting of sensorimotor (N = 22) or motor (N = 18) UL therapy. Outcome measures: Action Research Arm test (ARAT) as primary outcome, and other motor and somatosensory measures were assessed at baseline, post-intervention and after 4 weeks follow-up. Results: No significant between-group differences were found for change scores in ARAT or any somatosensory measure between the three time points. For UL impairment (Fugl-Meyer assessment), a significant greater improvement was found for the motor group compared to the sensorimotor group from baseline to post-intervention [mean (SD) improvement 14.65 (2.19) vs. 5.99 (2.06); p = 0.01] and from baseline to follow-up [17.38 (2.37) vs. 6.75 (2.29); p = 0.003]. Conclusion: UL motor therapy may improve motor impairment more than UL sensorimotor therapy in patients with sensorimotor impairments in the early rehabilitation phase post stroke. For these patients, integrated sensorimotor therapy may not improve somatosensory function and may be less effective for motor recovery. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03236376.

Mismatch between observed and perceived upper limb function: an eye-catching phenomenon after stroke.

PURPOSE: To investigate the relation between observed and perceived upper limb motor function in patients with chronic stroke. MATERIAL AND METHODS: We investigated 32 patients at six months after stroke with the Fugl-Meyer Assessment (observed function) and hand subscale of the Stroke Impact Scale (perceived function). Spearman correlation was calculated to relate observed and perceived function. Through cut-off scores, we divided our sample in low (Fugl-Meyer Assessment <31/66) and good observed function, and low (hand subscale of Stroke Impact Scale <61/100) and good perceived function. Scatterplot and hierarchical clustering analysis was conducted to detect distinct groups. RESULTS: A strong positive relation was found between observed and perceived function (r = 0.84). Three groups could be identified; a "low match group" of patients with low observed and low perceived function (n = 11, 34%), a "good match group" containing patients with good observed and good perceived function (n = 15, 47%), and a "mismatch group" comprising patients with good observed but low perceived function (n = 6, 19%). CONCLUSIONS: In our chronic sample, one in five patients showed good upper limb observed but low perceived function. Measuring both observed and perceived arm and hand function seems warranted together with considering a differential therapy approach for the distinct groups. Implications for rehabilitation A considerable group of patients in the chronic phase post-stroke have good motor function in their affected upper limb, but nevertheless perceive a restricted ability. In order to identify a mismatch in people with chronic stroke, both observed and perceived upper limb motor function should be assessed. Besides common measurement tools for observed function like the Fugl-Meyer Assessment, perceived function can be evaluated by means of the hand function section of the Stroke Impact Scale. For patients with good observed but low perceived function, an additional rehabilitation strategy should be considered, potentially including awareness of ability and a self-efficacy approach.

Does sensorimotor upper limb therapy post stroke alter behavior and brain connectivity differently compared to motor therapy? Protocol of a phase II randomized controlled trial.

BACKGROUND: The role of somatosensory feedback in motor performance has been warranted in the literature. Although sensorimotor deficits are common after stroke, current rehabilitation approaches primarily focus on restoring upper limb motor ability. Evidence for integrative sensorimotor rehabilitation approaches is scarce, as is knowledge about neural correlates of somatosensory impairments after stroke and the effect of rehabilitation on brain connectivity level. Therefore, we aim to investigate changes in sensorimotor function and brain connectivity following a sensorimotor therapy program compared to an attention-matched motor therapy program for the upper limb after stroke. METHODS: An assessor-blinded randomized controlled trial will be conducted. Sixty inpatient rehabilitation patients up to eight weeks after stroke will be included. Patients will be randomized to either an experimental group receiving sensorimotor therapy or a control group receiving attention-matched motor therapy for the upper limb, with both groups receiving conventional therapy. Thus, all patients will receive extra therapy, a total of 16 1-h sessions over four weeks. Patients will be assessed at baseline, after four weeks of training, and after four weeks of follow-up. Primary outcome measure is the Action Research Arm Test. Secondary outcome measures will consist of somatosensory, motor and cognitive assessments, and a standardized resting-state functional magnetic resonance imaging protocol. DISCUSSION: The integration of sensory and motor rehabilitation into one therapy model might provide the added value of this therapy to improve sensorimotor performance post stroke. Insight in the behavioral and brain connectivity changes post therapy will lead to a better understanding of working mechanisms of therapy and will provide new knowledge for patient-tailored therapy approaches. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03236376 . Registered on 8 August 2017.

Functional network connectivity is altered in patients with upper limb somatosensory impairments in the acute phase post stroke: A cross-sectional study.

BACKGROUND: Aberrant functional connectivity in brain networks associated with motor impairment after stroke is well described, but little is known about the association with somatosensory impairments. AIM: The objective of this cross-sectional observational study was to investigate the relationship between brain functional connectivity and severity of somatosensory impairments in the upper limb in the acute phase post stroke. METHODS: Nineteen first-ever stroke patients underwent resting-state functional magnetic resonance imaging (rs-fMRI) and a standardized clinical somatosensory profile assessment (exteroception and higher cortical somatosensation) in the first week post stroke. Integrity of inter- and intrahemispheric (ipsilesional and contralesional) functional connectivity of the somatosensory network was assessed between patients with severe (Em-NSA< 13/32) and mild to moderate (Em-NSA> 13/32) somatosensory impairments. RESULTS: Patients with severe somatosensory impairments displayed significantly lower functional connectivity indices in terms of interhemispheric (p = 0.001) and ipsilesional intrahemispheric (p = 0.035) connectivity compared to mildly to moderately impaired patients. Significant associations were found between the perceptual threshold of touch assessment and interhemispheric (r = -0.63) and ipsilesional (r = -0.51) network indices. Additional significant associations were found between the index of interhemispheric connectivity and light touch (r = 0.55) and stereognosis (r = 0.64) evaluation. CONCLUSION: Patients with more severe somatosensory impairments have lower inter- and ipsilesional intrahemispheric connectivity of the somatosensory network. Lower connectivity indices are related to more impaired exteroception and higher cortical somatosensation. This study highlights the importance of network integrity in terms of inter- and ipsilesional intrahemispheric connectivity for somatosensory function. Further research is needed investigating the effect of therapy on the re-establishment of these networks.

Is There Full or Proportional Somatosensory Recovery in the Upper Limb After Stroke? Investigating Behavioral Outcome and Neural Correlates.

BACKGROUND: Proportional motor recovery in the upper limb has been investigated, indicating about 70% of the potential for recovery of motor impairment within the first months poststroke. OBJECTIVE: To investigate whether the proportional recovery rule is applicable for upper-limb somatosensory impairment and to study underlying neural correlates of impairment and outcome at 6 months. METHODS: A total of 32 patients were evaluated at 4 to 7 days and 6 months using the Erasmus MC modification of the revised Nottingham Sensory Assessment (NSA) for impairment of (1) somatosensory perception (exteroception) and (2) passive somatosensory processing (sharp/blunt discrimination and proprioception); (3) active somatosensory processing was evaluated using the stereognosis component of the NSA. Magnetic resonance imaging scans were obtained within 1 week poststroke, from which lesion load (LL) was calculated for key somatosensory tracts. RESULTS: Somatosensory perception fully recovered within 6 months. Passive and active somatosensory processing showed proportional recovery of 86% (95% CI = 79%-93%) and 69% (95% CI = 49%-89%), respectively. Patients with somatosensory impairment at 4 to 7 days showed significantly greater thalamocortical and insulo-opercular tracts (TCT and IOT) LL ( P < .05) in comparison to patients without impairment. Sensorimotor tract disruption at 4 to 7 days did not provide significant contribution above somatosensory processing score at 4 to 7 days when predicting somatosensory processing outcome at 6 months. CONCLUSIONS: Our sample of stroke patients assessed early showed full somatosensory perception but proportional passive and active somatosensory processing recovery. Disruption of both the TCT and IOT early after stroke appears to be a factor associated with somatosensory impairment but not outcome.

Somatosensory Impairments in the Upper Limb Poststroke: Distribution and Association With Motor Function and Visuospatial Neglect.

BACKGROUND: A thorough understanding of the presence of different upper-limb somatosensory deficits poststroke and the relation with motor performance remains unclear. Additionally, knowledge about the relation between somatosensory deficits and visuospatial neglect is limited. OBJECTIVE: To investigate the distribution of upper-limb somatosensory impairments and the association with unimanual and bimanual motor outcomes and visuospatial neglect. METHODS: A cross-sectional observational study was conducted, including 122 patients within 6 months after stroke (median = 82 days; interquartile range = 57-133 days). Somatosensory measurement included the Erasmus MC modification of the (revised) Nottingham Sensory Assessment (Em-NSA), Perceptual Threshold of Touch (PTT), thumb finding test, 2-point discrimination, and stereognosis subscale of the NSA. Upper-limb motor assessment comprised the Fugl-Meyer assessment, motricity index, Action Research Arm Test, and Adult-Assisting Hand Assessment Stroke. Screening for visuospatial neglect was performed using the Star Cancellation Test. RESULTS: Upper-limb somatosensory impairments were common, with prevalence rates ranging from 21% to 54%. Low to moderate Spearman ρ correlations were found between somatosensory and motor deficits (r = 0.22-0.61), with the strongest associations for PTT (r = 0.56-0.61) and stereognosis (r = 0.51-0.60). Visuospatial neglect was present in 27 patients (22%). Between-group analysis revealed somatosensory deficits that occurred significantly more often and more severely in patients with visuospatial neglect (P < .05). Results showed consistently stronger correlations between motor and somatosensory deficits in patients with visuospatial neglect (r = 0.44-0.78) compared with patients without neglect (r = 0.08-0.59). CONCLUSIONS: Somatosensory impairments are common in subacute patients poststroke and are related to motor outcome. Visuospatial neglect was associated with more severe upper-limb somatosensory impairments.

Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits.

The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand.