15 minute read
The Brains Behind It
from 2024 RCSI Alumni Magazine
by RCSI
Against physical and psychological impacts on the brain, there's a team of defenders to protect it.
Every day, the most complex organ in the body is subject to an onslaught of attacks from physical, psychological and technological forces. Defending the brain against tumours and stroke, diseases such as epilepsy, Alzheimer’s and Motor Neurone Disease, and conditions including anxiety, depression and addiction, requires an army of experts, with each bringing their own arsenal of skills, techniques and research to bear on the physiology and function of the brain, and its relation both to the rest of the body and the world beyond.
As collaboration between disciplines becomes ever more fruitful, the potential for breakthroughs that will have an enormous impact on our ability to defend the brain against forces from both outside and within, makes this one of the most exciting areas of medical practice and research today. RCSI alumni with a wide variety of interests and expertise are at the forefront of this important work.
The Neuroscientist: Dr Cristina R. Reschke, Postgraduate Studies, Class of 2019
Dr Cristina R. Reschke is a Lecturer in the School of Pharmacy and Biomolecular Sciences and Funded Investigator within FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases at RCSI. She trained as a Clinical Pharmacist and holds an MSc and PhD in Pharmacology, both focused on the treatment of epilepsy. Cristina’s major discoveries are on microRNA-based therapies and the pre-clinical development of novel oligonucleotide delivery systems. She has received a number of prestigious international awards, including the Harinarayan Young Neuroscientist Award and the Grass Foundation Young Investigator Award, endowed by the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES), respectively. Cristina is the inaugural recipient of the CURE Epilepsy Cameron Boyce Foundation Taking Flight Award and currently holds a clinical research grant from the Dravet Syndrome Foundation. Cristina serves in a number of ILAE task forces and currently serves as the Academic member for the Irish Epilepsy League Council.
Defending the brain by developing next-generation treatments for epilepsy
As a neuroscientist I try to understand the cellular and molecular mechanisms of the brain and how changes in these intricate networks may impact and lead to the development of diseases. My main focus is on epilepsy, which represents a pressing and widespread medical challenge, impacting around 1% of the worldwide population. It is a complex neurological disorder with a spectrum of diseases characterised by focal or generalised seizures and affects people of all ages. The current diagnostic landscape faces a 30% misdiagnosis rate, and existing treatments often provide only symptom suppression, leading to high refractory rates and debilitating side-effects. Surgical interventions are limited, apply to a minority and do not tackle co-morbidities. Together with my team, I am working towards the development of next-generation treatment and diagnosis for different types of epilepsies through innovative approaches.
Working to understand the importance of the circadian clock
In the epilepsy field we are moving towards treatments that can modify the course of the disease rather than treat isolated symptoms. Leveraging from extensive preclinical work, we expect to see progress towards clinical trials with antisense oligonucleotides and gene therapies. These modalities of advanced therapies, however, require the precise detection of not only the pathogenic triggers, but also their location (brain region and cell type) and their dynamics. More than 80% of the protein-coding genes, which may be targets of these therapeutic modalities, are known to be controlled by the circadian clock, rhythmically oscillating approximately every 24 hours. Each brain region uniquely contributes to this oscillation since each brain cell type has its own clock. Unpublished data from my lab shows that prolonged seizures are able to remap this expected oscillatory signature in the hippocampus, an area very relevant for the most common type of drug-resistant epilepsy. To add intricacy, clinical evidence shows that more than 90% of people with epilepsy present circadian rhythmicity in their seizure occurrence. It means, when they present seizures, these may mostly cluster only at day or at night time. Overall, these dynamics seem to be highly specific to each person and we hope to discover, in the future, the underlying molecular changes that currently are not known.
The Neuropathologist: Professor Michael Farrell, Medicine, Class of 1974
Professor Michael Farrell graduated from RCSI with a degree in medicine before undertaking an internship at the Richmond Hospital, Dublin. Following completion of the MRCPI, Professor Farrell began his training in pathology at St Vincent’s Hospital, Dublin and later at the Westminster Hospital in London. After the MRCPath, he began a career in neuropathology at the University of Western Ontario, Canada where he also undertook a fellowship in neuroimmunology. Later, Michael succeeded Professor Paddy Bofin as Neuropathologist to the Richmond Hospital, moving to the new Beaumont Hospital in 1987. He was appointed the first Professor of Clinical Neurological Sciences at RCSI in 1996. Later, he became Dean of the Institute of Irish Clinical Neuroscience and was also Chairman of the Neuroscience Cogwheel at Beaumont Hospital. His interests include all aspects of clinical neuroscience but with particular interests in epilepsy, neurodegeneration and mitochondrial disease. He is a member of the American Association of Neuropathologists and the British Neuropathological Society as well as the International Society of Neuropathology. In 2023 Professor Farrell was the recipient of the RCSI Inspiring Educator Alumni Award.
Defending the brain through brain banking
Professor Francesca Brett and I co-founded The Dublin Brain Bank in 2008; it is currently under the directorship of Dr Jane Cryan, Consultant Neuropathologist at Beaumont Hospital. A collaboration between the Neuropathology Department of Beaumont Hospital and RCSI, it is based in RCSI Smurfit Building, Beaumont Hospital. Through supporting brain donation, the Dublin Brain Bank offers patients and members of the public the opportunity to support medical science in a very tangible manner. Donation of precious brain tissue facilitates research into neurological disorders, providing valuable information on the diagnosis and treatment of many common neurological diseases such as Alzheimer’s, Parkinson’s and Motor Neurone Disease, which will ultimately lead to improved quality of life for patients.
Learning from the study of the post-mortem brain
As we enter an era of potentially revolutionary treatments for all neurodegenerative diseases, it has never been more critical that the human brain continues to be studied after death. Only by doing so can we be sure not only that the original diagnosis was correct, but also that we can measure the contribution of other hidden, age-related conditions. The human brain displays enormous resilience and possesses massive functional reserves which go a long way towards explaining why the same pathologic process results in dementia in one person but not in another. For this reason alone, the post-mortem study of the clinically normal human brain is essential to provide a background against which we can measure the effects of age, prior trauma, hidden pathology, and the effectiveness of any new treatments. Much has been learned about the long term effects of brain trauma, but there are many individuals who have sustained concussive brain injury yet remain neurologically healthy into old life. We simply don’t have the answer to why this is so, hence the need to continue to study both the diseased and the healthy human brain after death using all of the latest research tools. Brain Banking is expensive, but the costs are miniscule when compared to the rising financial impact of neurodegeneration on our ageing but long-lived society.
The Neurosurgeon: Mr Darach Crimmins, Medicine, Class of 1993
After graduation from RCSI in 1993 and three years on general surgical scheme, Darach became a Fellow in 1996. Following SpR training in Yorkshire, and two years’ fellowship in Paris and London in paediatric neurosurgery, Darach worked as consultant neurosurgeon in Leeds General Infirmary 2005 to 2010. He is a Consultant Neurosurgeon in CHI at Temple Street Children’s Hospital and Beaumont Hospital since 2010. Darach is the National Lead for Paediatric Neurosurgery and examiner in Intercollegiate Board Neurosurgery Examinations (FRCS(SN)) since 2012.
Preventing further neurological injury
Children’s Health Ireland (CHI) Temple Street is an acute paediatric teaching hospital. The majority of the children we treat have hydrocephalus – congenital or for some other reason – requiring surgeries with or without implants. A further 10-15% present with brain tumours and need surgery before they have other treatment, such as chemotherapy. Two thirds of these patients have benign tumours and don’t need further treatment but any brain tumour can cause neurological injury. We treat patients with head and spinal trauma, cysts, and vascular conditions such as aneurysm, and we do epilepsy surgery. My job, and that of my colleagues, is to provide optimal neurosurgical care.
Tools that deliver improved patient outcomes
Perioperative diagnostic and planning imaging is improving all the time, and this is where incremental improvements can result in small breakthroughs. Brain surgery is complex and expensive and requires high-quality microscopes, laser and ultrasonic dissectors. Image guidance is key: we use intraoperative CT, MRI and ultrasound scanning and intraoperative EEG/ ECoG, all helping us navigate to the precise area of the brain that requires access. The aim is to be as minimally invasive as possible. We recently raised charity funding to acquire the right tool – an ultrasonic aspirator – to use with our neuro-endoscope (up to this we had been using one on loan from another hospital) so that patient recovery time is reduced – a young patient can go home without having to spend one or two weeks in hospital. This was a big leap forward. Our unit is one of very few in the UK and Ireland using this technology. There are new developments all the time, but it’s less about the breakthroughs and more about the hard work, efficiency and commitment of the teams at every level. At Temple Street, the culture is patient-focused and we get things done.
The Advanced Nurse Practitioner: Michelle Doyle, Nursing and Midwifery, Class of 2007, Postgraduate Studies, Class of 2017
Michelle Doyle is a registered advanced nurse practitioner (RANP) in paediatric neurosurgery. She has been working with the neurosurgery team since it commenced in Children’s Health Ireland (CHI) Temple Street in 2008. Michelle completed her diploma in General Nurse training at UCD/St Vincent’s Hospital, Postgraduate Sick Children’s Nursing at UCD/Temple Street, degree in Nursing and Midwifery at RCSI, Masters in Nursing/Clinical Health Sciences Education at Trinity College Dublin, Postgraduate Certificate in Neuroscience Nursing at RCSI/Beaumont Hospital, certificate in Nurse Prescribing at RCSI and Advanced Nurse Practice at Trinity College Dublin. Prior to her present role, Michelle worked for seven years as a clinical nurse educator on St Gabriel’s Ward, Temple Street, which specialises in caring for neurosurgery patients, and for three years as a paediatric neurosurgery nurse specialist. Michelle has led and facilitated many nursing study days/conferences at both a local and national level and is the founder and one of the module coordinators of the National Paediatric Neuroscience Module based in CHI at Temple Street/DCU. In 2020, Michelle and her neurosurgical nursing colleagues won CHI’s Extraordinary Clinical Team Recognition Award.
Defending the brain through caring for paediatric neurosurgery patients
As the only RANP for paediatric neurosurgery in the country, part of my role entails carrying out procedures traditionally only performed by neurosurgical registrars or consultants. These tasks include tapping cerebrospinal fluid (CSF) from ventricular access devices for premature babies and children with hydrocephalus, removing external ventricular drains and intracranial pressure probes, and obtaining CSF samples from external ventricular drains. Also, a substantial part of my role is assessing, prescribing and discharging neurosurgery patients on a daily basis, ensuring they receive all the necessary education, support and expert advice.
Holistic care at Ireland’s first nurse-led paediatric neurosurgery clinic
I set up the first nurse-led paediatric neurosurgery clinic in Ireland in January 2020; it has been extremely successful to date. I review neurosurgical patients from 0-16 years old in the outpatient department. These include patients with hydrocephalus, head injuries and those requiring wound management advice. I established the National Neurosurgery Educational Roadshow alongside the neurosurgery team, visiting all the paediatric hospitals around the country, delivering expert talks on our specialty. I am hoping in the near future to be involved in setting up a concussion clinic for CHI.
The Physiotherapist: Geraldine O’Callaghan, Postgraduate Studies, Class of 2010
A specialist physiotherapist in stroke and neurology, Geraldine graduated from the University of East London with a BSc in Physiotherapy, and holds an MSc in Neurology and Gerontology from RCSI. Geraldine also has a Diploma in Project Management and Leadership. Currently, she is completing a PhD at RCSI as part of the iPASTAR (Improving Pathways for Acute STroke And Rehabilitation) programme. Before starting her PhD under the HRB Collaborative Doctoral Awards Programme (CDA) with iPASTAR, Geraldine worked as a senior physiotherapist in rehabilitation at the HSE and the National Rehabilitation Hospital in Dún Laoghaire. Her research interests include stroke and motor neurone disease, and she has published research in both areas.
Defending the brain through rehabilitation
As a physiotherapist with extensive experience in rehabilitation, my work focuses on defending against the physical impacts on the brain through applying rehabilitation techniques and developing innovative therapies. Techniques to maximise functional independence for individuals with neurological conditions include personalised exercise programmes, balance and coordination training, and motor skills practice. By stimulating neuroplasticity through targeted activities and interventions, I work to improve long-term outcomes for people with stroke and other neurological conditions. Additionally, I have co-created national guidelines for the physiotherapy management of motor neurone disease and co-developed an innovative strategy to support and improve the transition from hospital to home, following stroke. This dual focus on rehabilitation and innovation helps patients achieve better recovery and maintain a higher quality of life.
Advances in stroke care
Recent advances in stroke care have come about through comprehensive, systemic improvements which standardise care and enhance treatment outcomes. These advances include the implementation of national stroke plans; regular updating and dissemination of national and European stroke guidelines to ensure people with stroke receive the most effective and appropriate treatments; and the inclusion of people with lived experience, their families, and members of the public in research and quality improvement initiatives to develop tailored solutions to meet individual post-stroke needs.
The Psychiatrist: Dr John Cooney, Medicine, Class of 1986
A consultant psychiatrist working in liaison psychiatry based at St James’s Hospital, Dublin, John is a Clinical Associate Professor of Psychiatry at Trinity College Dublin. Early in his career, John was a Senior Registrar/Lecturer at the Maudsley Hospital and at St Bartholomew’s Hospital in London. He also worked at St Patrick’s Hospital, Dublin specialising in the treatment of mood disorders and as a consultant psychiatrist and Senior Lecturer at the South London & Maudsley NHS Trust. He was Clinical Director of the Haematology, Oncology, Palliative Care and Psychological Medicine Services at St James’s and a former Chair of the Medical Board. He has an MD on the relationship between stress and mental illness from the National University of Ireland. He is a Fellow of the Royal College of Physicians in Ireland and a member of the Royal College of Psychiatrists in London.
Defending the brain from decline
Brain insults arise from trauma – both psychological and physical – toxicity from drugs and alcohol, and acute and/or chronic disease processes, to name some of the more common sources. These all arise in my work as a general hospital (aka liaison) psychiatrist. Back in the mid-1980s when I graduated, the teaching was that brain development pretty much finished at around age 18. Since then, the concept of neuroplasticity – that experience alters brain structure and by extension brain function – is well established. Interventions –be they physical, psychological or social – have the potential to alter what the brain experiences. The consequences of altering the trajectory of emotional, behavioural and brain function can move the person from decline and decay to growth and regeneration. We see the toll that the many and varied insults take on brain function but many of the symptoms are non-specific manifestations of disturbance of brain function. Determining the origin of the symptoms therefore requires that we must systematically evaluate those symptoms to lead us to the correct intervention. It is more complicated as it is people we are talking about and so the colouring of a presentation will vary often for any given individual.
Evolution rather than revolution
I would say that in terms of psychiatric therapeutics, it’s a picture of evolution rather than revolution. We understand that pharmacological or acoustic/ emotional (psychotherapeutic) interventions all alter brain experience and have the potential to alter brain dysfunction, whether in terms of mood or behaviour for example. The correct sequencing of the available interventions and the demonstration of the efficacy of agents such as ketamine and psilocybin add further to the arsenal of options. Neuromodulation – originally with ECT, which is still one of the most effective treatment for severe life-threatening depression – now includes less invasive techniques such as transcranial magnetic stimulation and a number of variants therein. The current vogue for a trauma-focused approach to patients is welcome but must be balanced against the fact that trauma does not inevitably mean adverse outcomes but can lead to post-traumatic growth: that which doesn’t kill us can make us stronger. We should not forget the old lessons in the search for the new and exciting! ■
