Introduction to the protocol MEMORI-net

Background. With more than 1 million new cases/year, stroke represents one of the most urgent causes of intellectual and motor disability in European countries. Stroke can affect still productive persons, and therefore has a profound impact on the healthcare system, the families and the whole local economy. Although stroke is an acute vascular injury of the brain, it may result in disabilities in the whole body which require multidisciplinary practices of rehabilitation. Indeed, scientific studies have demonstrated that the combination of cognitive and motor training produces the best results in terms of patient recovery, however there is a lack of well-defined rehabilitation protocols that include these two dimensions.

Aims. This project aims at designing and testing a new Pathway of Diagnostic and Therapeutic Assistance for an integrated cognitive and motor rehabilitation protocol. Cognitive rehabilitation represents a valuable therapeutic option for improving patient cognitive abilities and faster positive adaptation in daily life and association with motor rehabilitation is known to promote brain plasticity and recovery of cognitive deficits.

Methods. Motor and cognitive rehabilitation protocols will be composed by different training modules selected considering the best gold standards in the field. Cognitive rehabilitation modules will focus mainly on the rehabilitation of attention-related processes and memory, since these functions are the most frequently affected by stroke. Neuromuscular stimulation combined with voluntary movement training is one of the most effective interventions for motor rehabilitation after stroke. After stroke, patients have damaged central nervous system (CNS) but the peripheral nervous system is undamaged. With electromuscular stimulation (EMS) it is possible to induce the contraction of muscles without the involvement of CNS and thus prevent the development of muscle atrophy. Our protocol of EMS is based on recent randomized controlled studies that treated stroke patients with EMS to strengthen different atrophied muscle groups. These protocols will be applied already in the early stages after the stroke. We will be using rectangular, fully compensated, bi-phasic impulses.

MEMORI-net PROPOSAL

We designed a prospective, randomized, non-blinded study of 2 months treatment to evaluate the efficacy of a combined motor and cognitive rehabilitation protocol for post-stroke patients. 


Source: G. Galli - Bibione 2019

The study includes the following phases:

  • T0 - Baseline and Screening (within 72 h after stroke):  subjects will be considered for the study if fulfilling inclusion criteria and then included in the study.  This phase includes first neuropsychological assesment (reduced battery of questionnaires), evaluation of inclusion/exclusion criteria, written informed consent by patients or their relatives, and blood laboratory tests and serum predictive biomarkers (as MMP).
  • T1 - Baseline and Therapy start (1-2 weeks after stroke, at clinical stabilization): At the beginning of the rehabilitation therapy a full battery of questionnaires will be filled in by patients and will be done a clinical evaluation. Laboratory tests for serum Biomarkers, genetic biomarkers of responsiveness to rehabilitation therapy (including BDNF polymorphisms) and pharmacogenomics for testing responsiveness to potential pharmacological therapies will be done. Patients’ cognitive functions will be assessed by psychologists in the neurology or in the rehabilitation ward at T1, on the day before the rehabilitation start, using a full battery of tests (See Intervention) for the area Language, Visuospatial attention, Working memory, Long-term memory, Executive functions. Moreover, sensorial dysfunctions and pain issues will be evaluated. Participants who at T1 showed only motor deficits and no cognitive ones will be enrolled in the rehabilitation program and will be tested at T2 whereas if they show moderate to severe aphasia or neglect they will not take part to the study.
  • T2 - Therapy checkpoint n. 1 (4 weeks from T1): it includes the same motor and cognitive assessments as in T1 and the same rehabilitation protocol A and B as T1.
  • T3 - Therapy checkpoint n.2 (at the end of rehabilitation = 5-12 weeks from T1): it includes the same motor and cognitive assessments as in T1, the same rehabilitation protocol A and B as T1 untill end of therapy, and also laboratory serum biomarkers assessment after the administration of rehabilitation.
  • T4 - Therapy Follow-up (at 3 months from the end of the rehabilitation): it includes the same motor and cognitive assessments as in T1.

The complete list of tests is visible in the following table:

TEST NAME T0 T1 T2 T3 T4
The Montreal Cognitive Assessment (MOCA) X     X X
The Frontal Assessment Battery (FAB) X     X X
Barthel Index X X X X X
NIH-NINDS X X X X X
Naming and word comprehension tasks (ENPA)   X X X X
Star cancellation test (BIT)   X X X X
Forward and backward Digit Span   X X X X
Forward and backward Corsi Span   X X X X
Short recognition memory for words and faces (Warrington)   X X X X
Trail Making Test (TMT-A and TMT-B)   X X X X
Brixton Test   X X X X
Stroop Test – short version   X X X X
Tower of London   X X X X
McGill questionnaire   X X X X
Neuropathic Pain Symptom Inventory (NPSI)   X X X X
Analysis of mechanical allodynia   X X X X
Mechanical allodynia, touch and temperature sensations tests   X X X X
Rankin modified scale   X X X X
Trunk Control Test TCT   X X X X
Fugl-Meyer Assessment   X X X X
MIQ-Revised Second version scale (MIQ-RS)   X X X X
Gait test with dual tasks (walking test)   X X X X
Senior fitness test with Grip strength   X X X X
Tensomyography (TMG)   X X X X
Ashwarth 5 points scale for spasticity   X X X X
Quantitative EEG with power spectrum analysis (PSD)   X X X X
Genetic markers of responsiveness to rehabilitation therapy (BDNF polymorphisms) X        
Pharmacogenomics for responsiveness to pharmacological pain therapies X        
Prognostic serum biomarkers of stroke outcome X     X  
Serum biomarkers of responsiveness to motor/cognitive rehabilitation   X   X  
Cognitive rehabilitation exercises   X X X  
Standard cognitive rehabilitation exercises   X X X  
Standard motor rehabilitation exercises   X X X  
Neurofeedback   X X X