Meet the Scientists: Dr Elisha Josev

By Sasha Nimmo

Dr Josev is a Research Officer, Neurodisability and Rehabilitation; a Research Psychologist, Environmental and Genetic Epidemiology and Honorary Research Fellow in the Department of Paediatrics at the University of Melbourne. Earlier this year Dr Josev published a study ‘Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome’ which found adolescents with ME and CFS (2006 Jason et al paediatric definition) had slower reaction times before cognitive exertion and even slower after exertion. Dr Josev presented her work at the Emerge conference in Victoria earlier this year (video).

What are you working on at the moment?
In addition to working clinically with younger children, I currently lead a small research team which is investigating short-term and long-term effects of paediatric ME/CFS on brain structure and function, in comparison with healthy children and adolescents. We are looking to see if we can identify novel brain biomarkers that may aid in diagnosis or prognosis of the illness, and to see whether these biomarkers may relate to the presence and/or severity of particular ME/CFS symptoms such as fatigue severity and level of cognitive functioning. At the moment, we are specifically looking into brain metabolites and brain microstructural properties that may reflect inflammation in the brain as a result of ME/CFS.

We are fortunate enough to have a research-dedicated 3-Tesla MRI scanner at MCRI. The state-of-the-art neuroimaging techniques are cutting-edge physical infrastructure used to image the brain and our team is also using the latest analysis pipelines to evaluate the brain from different perspectives and magnitudes. As an example, we are currently using fixel-based analysis which is a technique that aims to analyse microstructural and macrostructural properties of white matter axons in the brain – axons are like the telephone wires of the brain that facilitate communication between different brain regions. Through this type of analysis, we can evaluate the calibre of individual white matter fibre populations, through properties such as fibre density and fibre cross-section, and this can inform us about the efficiency of communication between different brain regions. We can then compare the efficiency of this brain communication between adolescents with ME/CFS and healthy adolescents to see whether any differences arise that may account for the ME/CFS symptoms experienced.

Our research team is also soon to begin working on some exciting new collaborative projects, looking into metabolic and proteomic disturbances in paediatric ME/CFS, as well as contributing to the establishment of an Australian ME/CFS biobank.

How do you divide your time between research and clinical practice?
I work part-time in clinical neuropsychology practice where I assess children who originally spent time in the hospital neonatal intensive care unit or special care nursery when they were born. Often these children were born very early, very small, and with multiple medical complications so I evaluate their developmental progress (particularly their brain, cognitive and behavioural development) and provide targeted help to families in instances where developmental progress is delayed or there is evidence of a developmental disability. 

My time is divided between clinical practice and research, which definitely keeps me very busy, but being a clinician-researcher is very rewarding. I would not have it any other way! It means my research is always informed by real-world problems, and my clinical practice is always in touch with the latest research. In my research, I also evaluate cognitive, brain and behavioural development in children and adolescents with a variety of conditions. My main interest is in investigating the neuropsychological effects of disruption to normal brain development, and the impact of fatigue and chronic health conditions on brain functioning and behaviour. I have been fortunate enough to work with a variety of clinical paediatric populations, but my main focus currently is in the paediatric ME/CFS population. 

How do you cope with the challenge of finding funding? I see this recent study was funded by ME Research UK.
In general, funding for scientific research is always difficult and extremely competitive in Australia, but this is even more so for ME/CFS research in particular. Most research funding for ME/CFS in Australia currently comes from charities and philanthropic bodies, and our team has been very fortunate to have been funded by overseas bodies such as ME Research UK, and national bodies such as the Judith Jane Mason and Harold Stannett Williams Foundation. We welcome the recent and upcoming announcements from the NHMRC about future targeted funding for ME/CFS research and look forward to more opportunities to continue our work. 

How long have you been involved with ME and CFS research? 
I am a relative newcomer to the ME/CFS field, having only worked in this field for the past three to four years, but am hoping to be able to continue my research into the neurobiological aspects of the condition in paediatric patients for the future. I first became involved in coordinating a pilot MRI study into paediatric ME/CFS at the Murdoch Children’s Research Institute with Dr Sarah Knight, but have since gone on to receive further funding to continue this research from different aspects.

Why is research into children so important?
Substantially less is known about how ME/CFS affects child and adolescent populations in comparison with adults. This is not ideal given that adolescence (particularly between the ages of 10 and 19 years of age) represents one of two age peaks for the incidence of ME/CFS. We know that ME/CFS during adolescence occurs at a time of significant change and development in terms of brain maturation, forming social and peer relationships, educational and academic skill attainment, and the start of teenagers gaining independence. Illness onset during this time can therefore result in a substantial reduction in functioning in these areas and a significant disruption educationally and socially. This may ultimately change a child’s developmental trajectory and could have longer-term effects in terms of occupational opportunities if young adults have to take extended periods of leave during study or work training. 

In contrast, while illness onset in adulthood still has a large impact on an individual’s life and future, it usually occurs at a time when most adults would have already well-established skills, careers, and personal relationships. This is why our team thinks it is important to invest time, energy and money into researching the etiology and effects of ME/CFS within a developmental context. In this way, we can hopefully optimise child and adolescent development and potentially limit the longer-term adverse effects on their future lives. 

Regarding research criteria, do you think the Jason et al Pediatric Criteria is useful and do you think different criteria is needed for children and for adults? 
To date, we have found the Jason et al criteria useful, which was developed by the International Association of CFS Pediatric Case Definition Working group (and adapted from the adult ME/CFS Canadian case definition or ‘Canadian Consensus Criteria’). However, I think more research is needed to determine how the illness might present differently in children compared with adults. We know that different medical conditions can have different impacts on the body and the brain depending on your developmental stage of being a child, adolescent, or adult. This is why it is important to study specific symptomatology and illness outcomes in paediatric ME/CFS patients to determine how they might differ from those adults who have had the conditions for many years. 

What is the most exciting finding so far?
Through our research studies, we have been very excited to provide evidence of both objective and subjective disturbances in sleep quality, cognitive abilities and school functioning in adolescents with ME/CFS compared with their healthy peers. We hope to find biological biomarkers that might account for or explain these disturbances, not only within the brain, but also within other aspects of body functioning such as metabolomics and proteomics.  

Is your work is making a difference to the way patients are treated?
We certainly hope so, and this is definitely the ultimate aim of our research at the Murdoch Children’s Research Institute; that is, to improve our understanding of paediatric ME/CFS using a systematic, interdisciplinary, and translational research approach to ultimately improve quality of care and outcomes for these patients. We are fortunate to be aligned with The Royal Children’s Hospital ME/CFS Rehabilitation Clinic through the Victorian Paediatric Rehabilitation Service. We try to meet regularly with the rehabilitation clinicians so that we can design research questions together and translate our research findings back to the clinic team. In this way, we hope that our research can ultimately inform diagnosis, prognosis, and treatment outcomes for the ME/CFS patients seen in this service, and across Australia. 

Do you intend to continue working on ME?
As long as research funding is available, I look forward to continue working with our team to further our research in the area of paediatric ME/CFS. Our team hopes to examine potential causes, biological markers, and long-term outcomes for children and adolescents with ME/CFS.

What are you most proud of in your career?
Being a successful recipient of funding, I am proud to continue to work with and support a small team of researchers who are passionate about investigating paediatric ME/CFS. I am also inspired to work with some of the brightest minds in paediatrics, and in a wider research environment that supports constant learning, mentorship, and development, with the bonus of using state-of-the-art neuroimaging techniques, analysis, and clinical paediatric assessment.

I am also proud that I have been able to develop good relationships with families participating in our research studies in order to learn more about their illness experience and ways in which we might be able to help. I am constantly amazed by the generosity of these families who donate their time to research, even when the research findings may not be translated into clinical practice quickly enough for their own children to benefit, but perhaps the research will benefit other families in the distant future. Even years after they have participated in our studies, I have been able to re-contact these families for advice and feedback on upcoming research projects to help inform and shape feasible research design and ideas. Our team is always sincerely grateful for their help.

What do you enjoying doing outside work?
Spending time with my family and friends, and enjoy visiting beaches, gardens, art galleries and music festivals when I can.