Following completion of his medical degree, Lorenzo Caciagli took a break from medical training to pursue research in epilepsy and neuroimaging, with the longer-term aim of combining a career in medicine and research.
In pursuit of this aim, he joined the PhD programme in Clinical Neurosciences at UCL Institute of Neurology in 2014, funded by a Brain Research UK PhD studentship.
He was awarded his PhD in July 2019, having completed a programme of work that has given important new insight into three common epilepsy syndromes.
There are a number of different types of epilepsy and epilepsy syndromes. These have different symptoms and features but have in common that they cause repeated seizures - like electrical storms that briefly interrupt the brain's normal activity.
In most patients seizures can be controlled with medication, but there are other cognitive, personal and psychiatric disturbances ('comorbidities') that detrimentally impact the lives of those affected. The underlying mechanisms of such disturbances, and their trajectories over time, are poorly understood and this hampers the development of treatments.
Magnetic resonance imaging (MRI) is a powerful tool for studying both the structure and function of the living brain. It can provide valid and measurable traits ('biomarkers') of disease processes, shedding light on the mechanisms of epilepsy and its comorbidities. Lorenzo used advanced MRI techniques to understand the underlying mechanisms of the comorbidities associated with epilepsy, and how they can potentially be treated.
His first project focused on temporal lobe epilepsy (TLE), the most common form of epilepsy. He wanted to understand whether there is progression of brain abnormalities associated with the disease i.e. do they get worse over time? He carried out an extensive review and analysis of previous structural MRI studies of TLE, involving more than 1,500 patients. Lorenzo's meta-analysis of these studies provides evidence that there is a cumulative loss of brain tissue both within and outside the temporal lobe, implying that TLE may be a progressive brain disorder. This work was the first synthesis and critical interpretation of more than 20 years of related research in the field and the results will help inform the future management of patients with drug-refractory TLE.
The second part of this project focused on convulsive seizures in TLE. Convulsive seizures are the most dramatic type of seizure. They involve the whole body, causing jerking and shaking, usually with a loss of consciousness, and are associated with an increased risk of injury and sudden unexpected death. Lorenzo used MRI to identify abnormal patterns of activity in an area of the brain known as the thalamus, laying the foundations for future work aimed at developing therapeutic approaches to prevent these seizures in TLE. Devising strategies to prevent these seizures may considerably reduce the risk of seizure-related injury and sudden unexpected death.
In his second project,Lorenzo focused on cognitive dysfunction in frontal lobe epilepsy (FLE). He used MRI to monitor brain activity during the execution of tasks that involved short-term memory and expressive language. He detected abnormal patterns of brain activity – with widespread reductions in activity in areas of the brain usually involved in these tasks, and disruptive engagement of a network of regions normally active at rest only.
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Lorenzo’s third project investigated brain structure and function in patients with Juvenile Myoclonic Epilepsy (JME) and their unaffected siblings. The aim was to identify heritable traits associated with the disease. He identified a number of abnormal traits that were present in both patients and unaffected siblings but that were more marked in patients, suggesting that they have relevance to the underlying disease mechanisms. This project thus advanced our understanding of the genetic effects associated with the disease.
This PhD studentship enabled Lorenzo to work for four years in the world-renowned National Hospital for Neurology and Neurosurgery in Queen Square, London, home to cutting-edge clinical and translational research. Pursing a PhD at Queen Square provided him with excellent supervision from world-renowned epilepsy experts and allowed him to lead innovative research projects, enrich his knowledge of epilepsy and its cognitive comorbidities, and gain substantial expertise in the use of neuroimaging techniques.
Lorenzo’s research has given important new insights to three common epilepsy syndromes. He has disseminated his findings widely via oral and poster presentations at national and international conferences, and the publication of numerous research manuscripts in prestigious journals. This will help to ensure that the research has maximum impact, underpinning ongoing research and driving changes in clinical practice.
Following completion of his PhD Lorenzo took up a postdoctoral research position at the University of Pennsylvania, where he is building on aspects of his PhD research.
In the long-term, he aspires to specialise as a neurologist, focusing his clinical and research work on advancing the understanding of epilepsy and, specifically, the translation of knowledge to the clinic to inform prognostic assessments, rehabilitation approaches, and the development of treatment strategies to improve patient care.
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