People affected by Stroke, Multiple Sclerosis (MS), and Parkinson's disease (PD) sharesevere and complex disabilities. Widespread neuro-inflammatory processes represent animportant pathogenetic component in all three conditions. The potential overlap withneurological complications of Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) infection has further contributed to the worsening of functional impairment.Since pharmacological therapies have limited or negligible effects in these disorders,neurorehabilitation plays a crucial role in restoring and maintaining adequate functionalabilities. In this context, dual-task strategies have attracted growing interest, buttheir effectiveness has not been adequately assessed in the above neurologicalconditions-and not at all in individuals with long-term sequelae of SARS-CoV-2 infection.Based on these premises, the objectives of this research project are: - to design rehabilitation strategies using the dual-task approach in its various forms (dual motor task, dual cognitive task, and combined motor-cognitive task) and to conduct feasibility tests in small groups of individuals affected by stroke, MS, PD, or long-term Coronavirus Disease 2019 (COVID-19) sequelae; - to apply the strategies found to be effective in larger trials involving participants with stroke, MS, or PD, with or without a history of SARS-CoV-2 infection; - to compare the outcomes of dual-task strategies with those obtained through conventional rehabilitation approaches.The activities planned within the project will be distributed among the fourparticipating operating units (OUs). OU1 (Santa Lucia Foundation) will be responsiblefor: 1. designing and validating dual-task rehabilitation strategies covering the three possible combinations of motor and cognitive activities (dual motor task, dual cognitive task, and combined motor-cognitive task); 2. assessing the feasibility of these strategies through a pilot study involving small groups of individuals with the aforementioned neurological conditions, including those with long-term outcomes of SARS-CoV-2 infection, and selecting the most suitable approaches.All four OUs will participate in the selection and enrollment of subjects for the trialphase.OUs 1, 3, and 4 (Collaborators to the project) will conduct the activities planned forthe experimental trial, including: 1. baseline assessment of enrolled participants using validated instruments to measure various motor and cognitive functions; 2. implementation of rehabilitation strategies based on the dual-task approach, making use of newly emerging technological devices; 3. follow-up assessments at the end of the treatment period and again three months later.Assessments will focus on motor functions such as gait and balance, cognitive functions,mood, the occurrence of domestic accidents, and the measurement of circulating biomarkersof neuroinflammation and neurodegeneration.Data collected throughout the different phases of the study will be compiled into asingle database, and statistical analyses will be performed by researchers from OU1.The interpretation of results will be carried out collaboratively by members of all OUs,and findings will be disseminated through participation in conferences and congresses, aswell as through publications in peer-reviewed international indexed journals.
Summary Description
Neurological diseases such as Stroke Outcomes (SO), Multiple Sclerosis (MS), and
Parkinson's disease (PD) cause complex and severe disabilities involving motor,
cognitive, and autonomic domains. Widespread neuroinflammation contributes to progressive
tissue damage in all three conditions. SARS-CoV-2 infection can further exacerbate
neurological deficits through inflammatory mechanisms, and its long-term effects may
aggravate pre-existing motor and cognitive impairments. Pharmacological therapies for
these diseases-and for post-COVID neurological sequelae-offer limited benefit; therefore,
neurorehabilitation represents a crucial therapeutic resource.
Dual-task approaches, which simultaneously target cognitive and motor functions, have
gained increasing interest because they better reflect daily life demands, align with
embodied cognition theories, and allow concurrent intervention on multiple deficit
domains. However, their efficacy has not been adequately assessed in SO, MS, and PD, and
has not been investigated at all in individuals with long-term neurological consequences
of SARS-CoV-2. This project aims to design and validate dual-task rehabilitation
strategies in these populations and compare their outcomes with those of conventional
rehabilitation.
Background and State of the Art
Individuals with SO, MS, and PD share multifaceted disabilities and underlying
neuroinflammatory processes. The additional impact of COVID-19, especially in cases with
persistent neurological manifestations, emphasizes the urgency of effective
rehabilitation methods. Preliminary work by the research team includes studies on
dual-task mechanisms and implementation in clinical settings, confirming feasibility and
theoretical relevance. Nonetheless, rigorous randomized, controlled-possibly
double-blind-trials are required to determine clinical efficacy.
Project Activities and Organization
The project includes the following integrated activities:
Design and validation of dual-task rehabilitation strategies, encompassing:
- dual motor tasks
- dual cognitive tasks
- combined motor-cognitive tasks Virtual and/or augmented reality environments will be
used when beneficial. Pilot feasibility study in small groups (5 per diagnostic
category: SO, MS, PD, long-term post-COVID) to assess applicability, patient
acceptance, and preliminary efficacy. Conducted by OU1.
Participant selection for the clinical trial (SO, MS, PD, with or without past SARS-CoV-2
infection) based on predefined inclusion/exclusion criteria. Conducted jointly by all
OUs.
Randomized controlled trial, conducted by OU1, OU3, and OU4, including:
1. Baseline motor, cognitive, and mood assessment using validated tools.
2. Implementation of dual-task strategies alongside standard rehabilitation, using
emerging technological devices.
3. Re-assessment at treatment completion and at 3-month follow-up.
Data integration in a unified database (OU1). Statistical analyses and interpretation,
including advanced methods such as artificial neural networks (OU1).
Dissemination through conferences and publications. Specific Aims Aim 1 - Development and
feasibility testing of dual-task strategies
Dual-task interventions will be designed by OU1 based on the three task combinations. A
preliminary feasibility phase will enroll 20 participants (5 SO, 5 MS, 5 PD, 5
post-COVID). Strategies demonstrating the best balance of efficacy and acceptability will
be selected for the clinical trial.
Aim 2 - Application of validated strategies in a randomized controlled trial A total of
48 participants (16 SO, 16 MS, 16 PD) will be recruited; for each condition, half will
have a history of SARS-CoV-2 infection with neurological symptoms persisting ≥4 weeks.
Additional inclusion/exclusion criteria ensure safety and feasibility.
Participants will be randomized into:
- Experimental group: standard rehabilitation (3/week) with dual-task training
(2/week, 30 min/session)
- Control group: standard rehabilitation with placebo low-resistance cycling (2/week,
30 min/session)
Aim 3 - Comparison of dual-task vs conventional rehabilitation outcomes
Outcome measures will be compared between:
- participants receiving standard with placebo therapy, and
- participants receiving standard with dual-task therapy.
Additionally, pre- and post-intervention blood samples will be analyzed for biomarkers of
neuroinflammation and neurodegeneration, providing complementary insight into
physiological changes associated with both rehabilitation modalities.
Appropriate statistical methods, including machine-learning-based analyses, will be used
to evaluate between-group and within-group differences.
Other: Dual Task exercise
Upper-limb sessions employ Virtual Art Therapy, during which the seated patient performs
virtual painting tasks that simultaneously stimulate motor control and cognitive
engagement. Balance training initially requires the patient to stand still with eyes
closed-sometimes on unstable surfaces-while performing serial subtraction tasks, followed
in later sessions by the Fukuda stepping test combined with the identification of male or
female voices presented in congruent or incongruent sequences. Motor imagery sessions
involve imagining the number of steps and time needed to reach a cone placed at varying
distances before executing the actual movement. Gait training, conducted overground or on
a treadmill, integrates various cognitive challenges: generating lists from semantic
categories, recognizing objects or colors in the environment, repeating short word
sequences for memory engagement, performing serial subtraction while walking, responding
to directional auditory stimuli.
Other: Physical therapy
Conventional exercises for upper and lower limbs motor rehabilitatiion
Inclusion Criteria:
- Diagnosis of stroke outcomes, Multiple Sclerosis (MS), or Parkinson's disease (PD).
- For stroke outcomes: patients must be able to walk independently for at least 6
minutes without resting.
- For MS: diagnosis according to the 2017 revised McDonald criteria;
relapsing-remitting or secondary progressive forms; age 25-65 years; Expanded
Disability Status Scale score between 2.5 and 6.0.
- For PD: idiopathic Parkinson's disease.
- For each neurological condition, half of the participants must have had Severe Acute
Respiratory Syndrome Coronavirus 2 infection with neurological symptoms attributable
to CNS involvement lasting at least 4 weeks.
- Ability to provide informed consent.
Exclusion Criteria:
- Cognitive or motor comobidity;
- Severe visual or hearing impairments that may compromise understanding of exercises
- Language impairments, such as aphasia
- Inability to walk independently
IRCCS Fondazione Santa Lucia
Roma 8957247, Roma, Italy
Marco Iosa, PhD, Associate Professor, Principal Investigator
IRRCS Santa Lucia foundation