Multi-Nutrient Supplementation as a Therapeutic Intervention in Ischaemic Stroke (MUST-IS)

Stroke is a significant cause of morbidity and disability worldwide. As the population ages, the economic impact of this condition is becoming very significant [1]. In the UK alone, the stroke estimated cost is £26 billion a year [2]. A stroke occurs every 5 min, which is more than 100,000 strokes in the UK each year [3]. Stroke is a leading cause of disability in the UK - almost two-thirds of stroke survivors in England, Wales and Northern Ireland leave the hospital with a disability [4].

The two main types of stroke are ischaemic (as a result of a blocked blood vessel) and haemorrhagic (due to bleeding in the brain). Acute ischaemic stroke (AIS) represents the most prevalent form of stroke (85%) and has been the target of numerous unsuccessful clinical drug trials. Therefore, AIS poses a major therapeutic challenge. The primary treatment comprises of intravenous delivery of thrombolytic agents such as Tissue Plasminogen Activator (tPA) and endovascular treatment (EVT) aiming at recanalization of an occluded vessel, and is usually only effective in patients who present within 4.5 hours of the onset of symptoms and 24 hours, for tPA and EVT, respectively [5, 6]. Yet, tPA has limited benefit in AIS patients with relatively large vessel occlusion (LVO), with only about 25% of the population achieving good clinical outcomes. Therefore, more recently, patients with proximal LVO have been treated with mechanical thrombectomy (MT), an endovascular technique that enables the restoration of blood flow by removing the obstructing blood clot from the affected artery with greater efficacy and a longer treatment window [6].

The standard treatment provided at present to AIS patients in the NHS in the post-acute phase consists of limited neurorehabilitation: 3 x 40 minute-long sessions with a therapist each week for 6 weeks in the acute stroke unit. This is divided between occupational therapy, physiotherapy, and speech and language therapy. Early intensive therapy in adults with AIS has been shown to have beneficial effects[7]. The current NHS rehabilitation standard may be suboptimal, as studies in the literature such as Zhu et al. found increased gains in patients after intensive (4 hours per day) versus standard (2 hours per day) rehabilitation support [8].

About 80% of acute stroke patients suffer from upper extremity (UE) motor impairments, and of those, hemiparesis is the most commonly exhibited damage. Upper limb complications commonly involve impaired sensation, movement and coordination. Among those, more than 50% retain some degree of hemiparesis months after stroke and remain unable to use their affected UE, which leads to impaired activities of daily living (ADL) and therefore compromised quality of life (QoL) [9, 10].

Souvenaid® (Nutricia, N.V., Zoetermeer, The Netherlands), is a commercially available food for special medical purpose that is used as a daily Oral Nutritional Supplement (ONS). It contains a specific nutrient combination, named Fortasyn Connect (FC), which has been shown to enhance synapse formation and function [11]. The product is currently used in the management of early Alzheimer's disease, as a specialised medical nutrient support, and it has been shown to preserve functional brain network organization, using electroencephalography (EEG), and also reduce cognitive decline [12, 13]. It is well established that stroke also disrupts complex neural network structure, and this is linked to disrupted neurological function. EEG is a non-invasive method of assessing cortical connectivity with high temporal sensitivity and it can be used to monitor neural network changes resulting from brain insults such as ischaemic stroke [14, 15]. In particular, Liu and colleagues recently showed that AIS patients display a weakened cortical connectivity, suggesting functional impairment in cortical information transmission [16].