32^nd European Neurology Congress July 22-24, 2019 London, UK

Inderjit Singh is a University Professor at the Medical University of South Carolina, USA. He is investigating the mechanisms of stroke and other neuroinflammatory diseases including vascular dementia associated with Alzheimer’s disease. Over the years, he has authored more than 300 high quality peer reviewed original articles and book chapters. He is continuously funded by the NIH for his studies on the disease mechanisms of neurodegeneration. Based on his credentials in neurodegenerative studies; he was awarded Jacob Javits Award for meritorious research in neurological sciences by NINDS/NIH (2002-2009). One of the goals is to evaluate a stroke drug therapy using clinically relevant stroke mouse models of cerebral ischemia and reperfusion (IR) and permanent ischemia (IS). The focus of the present study is on functional recovery and the mechanisms regulated by S-nitrosylation of HIF-1α using an effi cient S-nitrosylating agent S-nitrosglutathione (GSNO). GSNO is a natural component of the human body and its exogenous administration in human studies is not associated with adverse effects. In neuroinflammatory diseases, the levels of S-nitrosylation are decreased due to increased formation of peroxynitrite from NO and superoxide thus S-nitrosylation-mediated cellular functions are dysregulated. Presently, we are investigating neuroprotection/neuro-recovery therapy using GSNO in stroke, TBI and SCI.

Stroke is the leading cause of disability worldwide. It immediately sets into motion various neurodegenerative mechanisms including excitotoxicity and calcium dysregulation leading to infl ammatory/nitoxidative-mediated injury mechanisms. Our studies with a rat model of ischemia and reperfusion (1/R) show that an exogenous treatment with S-nitrosoglutathione (GSNO), a multi-targeting naturally-occurring compound provides neuroprotection as well as stimulates neurorepair and aids functional recovery. Stroke was induced by middle cerebral artery occlusion for 60 min followed by reperfusion followed by drug (GSNO) treatment at various time points after reperfusion. The studies show that GSNO-mediated targeting of neuronal nitric oxide synthase/peroxynitrite/calpains and inflammatory NF-KB mechanisms provides protection against neurodegeneration during acute stroke injury. Furthermore, GSNO-mediated mechanisms also stimulated neurorepair process via targeting HIF-la/VEGF/PECAM-1 as well as BDNF/CNTF signaling pathways to promote recovery of motor and neurological functions during the chronic disease of stroke. These studies document that targeting of S-nitrosylating mechanisms is potentially attractive therapy for stroke patients. In clinical settings, GSNO is of even greater relevance to stroke therapy because it additionally shows antiplatelet, anti-embolization and vasodilatory properties in humans. Based on the efficacy of GSNO in our preclinical studies using animal models of stroke and absence of toxicity in human uses, we submit that GSNO is a promising drug candidate to be evaluated for human stroke therapy and other neurodegenerative diseases treatment.

Annie Weir is the Director of Impact Research NZ and an Honorary Academic with the School of Critical Studies in Education, Faculty of Education, University of Auckland. Dr. Weir has worked in research and evaluation in New Zealand and the UK for over 20 years and her interests include: healthcare management, quality assurance in higher education, third sector social services provision and building organisational capacity.

Background: Two case studies were undertaken to determine the eff ectiveness of a) home support and b) day programmes that were designed to support older people living with dementia to remain at home in their community. Home support programmes provide services for both the person living with dementia and their main caregivers. These services are aimed at optimising client functioning and independence as well as promoting healthy daily routines, exercise, social interaction and support for clients to undertake their own daily needs. Typically day programmes provide a range of psychosocial and physical activities aimed at maximising client independence and importantly provide respite for caregivers.

 

Methods: A mixed method approach was used to determine the eff ectiveness of home support programmes. The first phase included an international literature review that identified a range of positive outcomes for clients receiving restorative home support such as improved functioning and better quality of life. The second phase included 1:1 interviews, focus groups and surveys with key stakeholders to elicit their views on the elements that make up eff ective home support. For the day programme research a mixed methods approach was also employed including an international literature review, document analysis, interviews, focus group, online survey, site observations and a photovoice exercise. Participants included multiple stakeholders including service funders, those delivering the service, clients and their caregivers. Quantitative survey data from both studies was reported using descriptive statistics and inductive thematic pattern analysis was performed on the qualitative data.

 

Results: Ten key factors of effective home support services were identified under three broad categories: 1) Client and Caregivers 2) Community and 3) Organisational. The research revealed that eff ective day programmes comprised five core elements, including activities aimed at improved client functioning; caregiver benefits; workforce capability; cultural responsiveness; and service processes. Reporting and auditing processes as well as surveys are reportedly used as methods to measure the quality of outcomes of day programmes.

 

Conclusions: The findings from both studies raise issues firstly around what constitutes effective restorative home support and secondly around the effectiveness of day programmes and may inform international debate and lead to better outcomes for people living with dementia.

Ann Ali Abdelkader Hanafy has completed her MD at the age of 30 years from Cairo University and postdoctoral studies from Cairo University School of Medicine. She is a Professor of Clinical Neurophysiology and the President of Egyptian Clinical Neurophysiology Society. She has published more than 100 papers in local and international journals.

Repetitive transcranial magnetic stimulation is non-invasive brain stimulation to the motor cortex. It can alter excitability of the brain after stroke by modulating cortical activity. At low frequencies (1 HZ or less), it has an inhibitory effect, whereas at high frequencies (5-25 HZ), it is able to enhance cortical excitability. As it produces long-lasting effects which persist past the initial period of stimulation through long-term potentiating (LTP) and long-term depression (LTD) (Chen et al., 2008).

 

Following stroke, the brain undergoes various stages of recovery where the central nervous system can reorganize neural circuits (neuroplasticity) both spontaneously and with the aid of behavioral rehabilitation and non-invasive brain stimulation (Auriat, et al., 2015).

 

Motor deficits in patients after stroke are due to a reduced output from the affected hemisphere and excess transcallosal inhibition of the affected hemisphere from the unaffected hemisphere. Therefore, using rTMS, could improve motor deficits by increasing the excitability of the affected hemisphere or inhibition of the unaff ected hemisphere and so the interhemispheric inhibition, through increasing or decreasing the excitability of the neuronal circuits, which is called neuroplascity and so motor recovery after stroke (Murase et al.,2004).

 

Cortical plasticity can be manipulated to improve stroke outcome by numerous techniques such as task-oriented physiotherapy. Task oriented exercise is assumed to learn patients (depending on the idea that learning is the basis of neuroplasticity) by allowing them to try solving problems actively by providing them with a functional task, instead of having them repetitively practice the normal patterns of movements. It is an approach suggested to be an efficient treatment

method, it consists of tasks that encourage various functional activities and help enhance patient's ability to perform daily activities and thus helping motor recovery after stroke (Yoo and Park, 2015). For continuous motor improvement, it is important to impart additional motor training while repetitive trans cranial magnetic stimulation modulates the neural network between both hemispheres and remodels work in the affected hemisphere (Takeuchi and izumi., 2012).

 

Researchers have tested the efficacy of HF rTMS over the affected hemisphere and efficacy of LF-rTMS over the unaffected hemisphere for patients post stroke (Khedr et al., 2009; Emara et al., 2010; Chang et al., 2010). Takeuchi et al., (2009) and Sung et al., (2013) hypothesized the safety, feasibility and efficacy of applying bilateral rTMS; HF- and LFrTMS in patients with chronic stroke. In the present study we hypothesized that the combined application of HF-rTMS over the affected hemisphere and LF-rTMS over the unaff ected hemisphere as bilateral rTMS may facilitate motor functional recovery in patients with acute stroke. The present study was conducted on different types; ischemic, hemorrhagic and embolic stroke, different sites; supra and infratentorial stroke and associated co-morbidities; ischemic heart disease, vasculitis and atherosclerosis.