Distinguishing Distinct Neural Systems for Proximal vs Distal Upper Extremity Motor Control After Acute Stroke

Abstract

Background and objectives: The classic and singular pattern of distal greater than proximal upper extremity motor deficits after acute stroke does not account for the distinct structural and functional organization of circuits for proximal and distal motor control in the healthy CNS. We hypothesized that separate proximal and distal upper extremity clinical syndromes after acute stroke could be distinguished and that patterns of neuroanatomical injury leading to these 2 syndromes would reflect their distinct organization in the intact CNS.

Methods: Proximal and distal components of motor impairment (upper extremity Fugl-Meyer score) and strength (Shoulder Abduction Finger Extension score) were assessed in consecutively recruited patients within 7 days of acute stroke. Partial correlation analysis was used to assess the relationship between proximal and distal motor scores. Functional outcomes including the Box and Blocks Test (BBT), Barthel Index (BI), and modified Rankin scale (mRS) were examined in relation to proximal vs distal motor patterns of deficit. Voxel-based lesion-symptom mapping was used to identify regions of injury associated with proximal vs distal upper extremity motor deficits.

Results: A total of 141 consecutive patients (49% female) were assessed 4.0 ± 1.6 (mean ± SD) days after stroke onset. Separate proximal and distal upper extremity motor components were distinguishable after acute stroke (p = 0.002). A pattern of proximal more than distal injury (i.e., relatively preserved distal motor control) was not rare, observed in 23% of acute stroke patients. Patients with relatively preserved distal motor control, even after controlling for total extent of deficit, had better outcomes in the first week and at 90 days poststroke (BBT, ρ = 0.51, p < 0.001; BI, ρ = 0.41, p < 0.001; mRS, ρ = 0.38, p < 0.001). Deficits in proximal motor control were associated with widespread injury to subcortical white and gray matter, while deficits in distal motor control were associated with injury restricted to the posterior aspect of the precentral gyrus, consistent with the organization of proximal vs distal neural circuits in the healthy CNS.

Discussion: These results highlight that proximal and distal upper extremity motor systems can be selectively injured by acute stroke, with dissociable deficits and functional consequences. Our findings emphasize how disruption of distinct motor systems can contribute to separable components of poststroke upper extremity hemiparesis.

Figure 1. Upper-Extremity Motor Impairment and Strength Are Bimodal and Closely Related After Acute Stroke

(A) Histograms of total upper extremity Fugl-Meyer (UE-FMA, motor impairment) and shoulder abduction finger extension (SAFE, strength) scores for n = 141 consecutively recruited patients with upper extremity weakness after acute stroke. X-axis shows severity ranges of upper extremity motor impairment, as defined in the study conducted Woytowicz et al. (B) Plot showing UE-FMA ranges (mean ± SD) for each level of total SAFE score. The relationship between upper extremity motor impairment and strength was as follows: Spearman rank correlation coefficient, ρ = 0.9, p < 0.001.

Figure 2. Preservation of Distal Motor Control Is Common After Acute Stroke and Related to Better 90-Day Functional Outcomes

(A) Boxplots (light gray boxes, in background) of normalized proximal (flexor synergy, items 3–8) and distal (hand, items 24–30) subscores of the upper extremity Fugl-Meyer are show in light gray. Superimposed are lines connecting the proximal and distal subscores for individual patients (the weighting of the line is scaled to the number of patients represented). Patients for whom proximal individuation > distal individuation (i.e., relatively preserved shoulder and elbow movements) are shown in orange. Patients for whom distal individuation > proximal individuation (i.e., relatively preserved hand and finger movements) are shown in blue. Green and yellow lines are patients for whom there was no gradient of proximal to distal motor control (PI-DI = 0). This occurred only in patients for whom there was either no movement (green) or complete movement (yellow) at proximal and distal segments. (B) Scatterplots of normalized distal-proximal gradient vs 90-day upper extremity function (Box and Blocks) and global function (modified Rankin Scale, mRS). Individual patients for whom PI > DI are shown in orange and DI > PI are shown in blue. A higher distal-proximal gradient (DI > PI) acutely was related to better 90-day upper extremity and global function.

Figure 3. Proximal vs Distal Upper Extremity Motor Deficits Are Associated With Unique Stroke Injury Patterns

(A) Stroke lesion overlap map for 141 study participants. Color bar (right) shows the number of lesions overlapped and scaling with dark blue to red showing an increasing overlap. Separate VLSM t-maps were first generated for proximal individuation (PI) and distal individuation (DI) scores, flexor synergy and hand subscores of UE-FM, respectively. The difference (t-map_diff) in raw t-maps (PI – DI in gradient orange and DI – PI in gradient blue) is shown in (B). This map has positive values (orange) where the association between proximal scores and voxel injury exceeds the association between distal scores and voxel injury and, conversely, negative values (blue) where the association between distal scores and voxel injury exceeds the association between proximal scores and voxel injury. Color bar with t-statistic range is shown at the bottom of the figure. Maximal voxelwise differences within t-map_diff identified by permutation statistics are shown in (C).