Riconcettualizzare il concetto di Prognosi del recupero motorio dopo riabilitazione dell’arto superiore in pazienti con ictus

Reconceptualizing the concept of Prediction of rehabilitation-induced upper limb motor recovery, after stroke: a multi-dimensional and multi-modal research project.

Autori

Silvia Salvalaggio (IRCCS San Camillo Hospital, Venice, Italy)

Simone Gambazza (University of Milan, Italy)

Silvia Gianola (IRCCS Istituto Ortopedico Galeazzi, Milan, Italy)

Greta Castellini (IRCCS Istituto Ortopedico Galeazzi, Milan, Italy)

Nicola Filippini (IRCCS San Camillo Hospital, Venice, Italy)

Marco Zorzi (University of Padova, Italy)

Andrea Turolla (University of Bologna, Italy)

Introduction

Prognosis of recovery has always covered an important role in medicine, due to its relevance for monitoring and interpreting patients’ achievements over time. After stroke, clinicians, patients and caregivers always ask what is likely to be expected for their clinical conditions and life in the future, and what the best therapeutic options might be for them. Even research in rehabilitation has always attempted to predict motor recovery by studies assessing and measuring functional aspects of movement. What is missing so far, is that we do not know how rehabilitation interventions may change the pattern of recovery, causing uncertainty on the potential of recovery of each patient, in response to specific interventions. In this perspective, being familiar with interpreting initial signs and symptoms, selecting the most appropriate assessment strategy and using prediction models is pivotal to be timely and clinically efficient.

Methods

With the aim of introducing a novel concept of prediction, focused on the expected recovery in response to rehabilitation rather than spontaneous recovery, I conducted three types of studies (i.e. work-packages, WP) designed to identify potential predictive factors and investigate the impact of different doses and modalities of therapy. In particular:

WP1: Systematic Review with Proportional meta-analyses. Longitudinal-single-cohort studies on patients undergoing rehabilitation after stroke were included. Predictive features investigated in the included studies were reported. The primary outcome was the Fugl-Meyer Assessment for Upper Extremity, and effect sizes (ES) of different rehabilitation doses were calculated.
WP2: Retrospective study design. Inpatients with first unilateral stroke, without time restrictions from onset, and undergoing at least 15 h of rehabilitation were enrolled. Data on dose and modalities of rehabilitation received, together with motor and cognitive outcomes before and after therapy, were collected. Fugl–Meyer values for the Upper Extremity were the primary outcome measure. Logistic regression models were used to detect any associations between UL motor improvement and motor and cognitive-linguistic features at acceptance, regarding dose of rehabilitation received.
WP3: Longitudinal cohort study. Stroke survivors were assessed before and after a period of rehabilitation, using motor, cognitive, magnetic resonance imaging and transcranial magnetic stimulation measures. We investigated the association between dose of rehabilitation and UL-response (i.e. FMA-UE), using ordinary least squares regression as primary analysis. To obtain unbiased estimates, adjusting covariates were selected using directed acyclic graph.

Results

WP1: Only 6% of the included studies (N = 141) investigated predictive factors. Studies providing more than 30 hours of therapy induced small to large clinical effect (ES from 0.38 to 0.88). Task-oriented approach led to the largest effect, both in the subacute (ES=0.88) and chronic (ES=0.71) phases. Augmenting interventions provided higher effect in the chronic rather than subacute phase. Integrity of the corticospinal tract, preservation of arm motor function and specific genetic biomarkers were found to be associated with motor recovery.
WP2: Thirty-five patients were enrolled and received 80.57 ± 30.1 h of rehabilitation on average. Manual dexterity, level of independence and UL motor function improved after rehabilitation, with no influence of attentive functions on motor recovery. The total amount of rehabilitation delivered was the strongest factor (p = 0.031) influencing the recovery of UL motor function after stroke, whereas cognitive-linguistic characteristics were not found to influence UL motor gains.
WP3: Baseline FMA-UE was the only factor associated with motor recovery (95%CI: 0.83 to 1.15). Attention emerged as a confounder of the association between rehabilitation and FMA-UE, influencing both rehabilitation and UL-response.

Discussion and Conclusion

All the results of this doctoral thesis can be summarised in the following key findings for stroke rehabilitation and recovery:

Patients’ demographic characteristics are not associated with UL motor outcomes, in stroke survivors.
Response to rehabilitation interventions for UL is driven by brain lesion characteristics, genetics and residual motor function at baseline.
Higher doses of rehabilitation provide higher effect on UL motor function in the chronic phase.
Attentive function is a key factor in predicting UL motor rehabilitation-driven recovery.
Association between doses of rehabilitation and prediction of UL motor recovery needs to be deeper investigated.
Priming interventions:
- Provide small effect for low dose of treatment (0-10 hours), moderate effect when at least 10 hours are delivered, in the chronic phase.
- Provide the main effect between 10 to 30 hours, higher doses do not provide adjunctive effects, in the chronic phase.
Augmenting interventions:
- provide more beneficial effect in the chronic rather than subacute phase, when at least 10 hours are delivered (moderate effect).
- independently by the dose, in the subacute phase, can provide small effects.
Task-oriented interventions
- provide the most beneficial effect (large effect) compared to other techniques, independently by the phase.

REFERENCES

Daly JJ, McCabe JP, Holcomb J, et al. Long-Dose Intensive Therapy Is Necessary for Strong, Clinically Significant, Upper Limb Functional Gains and Retained Gains in Severe/Moderate Chronic Stroke. Neurorehabil Neural Repair 2019; 33: 523-537. 2019/05/28. DOI: 10.1177/1545968319846120.

Coupar F, Pollock A, Rowe P, et al. Predictors of upper limb recovery after stroke: a systematic review and meta-analysis. Clin Rehabil 2012; 26: 291-313. 2011/10/26. DOI: 10.1177/0269215511420305.