Attracting over 6,000 neurologists from countries worldwide, the European Academy of Neurology (EAN) 2019 Congress was a hive for the sharing of knowledge, cementing itself as the largest general neurology congress in Europe. As host of the Nobel Peace Prize ceremony, the Norwegian capital of Oslo seemed to be the perfect city to host such an event, in which the coming together of neurologists from all over the world to combat the challenges that are currently facing the field is of utmost importance. A strong history of neurology is present in Norway, including great minds such as Fridtjof Nansen, who, amongst other outstanding achievements, defended the first Norwegian PhD for neuroscience in 1888, and Georg Herman Monrad-Krohn, a world-renowned neurologist best known for his masterpiece “The Clinical Examination of the Nervous System”.
Following the screening of a 5-year anniversary video showcasing the growth and progress of the congress, Prof Erik Taubøll welcomed delegates from around the world to his city of birth, Oslo. Those in the audience listened in awe as Prof Günther Deuschl recounted the fascinating previous 5 years of EAN, instilling pride in all that EAN had already achieved and looking forward to the great possibilities the young congress has. Prof Edvard Moser, a recipient of a Nobel prize in Physiology or Medicine in 2014, delivered a world-class opening lecture regarding his latest work on the different types of positioning cells within the brain and how they work together with neural codes form the entorhinal cortex to facilitate episodic memories. He not only explained how these cells monitor direction, place, speed, and location, but also how when connections between these cells are disrupted, spatial-temporal orientation symptoms related to neurological diseases, such as Alzheimer’s, can occur.
Presentation of ground-breaking research was evident in the abundance of abstracts at this year’s congress. Covering a staggering 31 topics, including the big 7 (epilepsy, stroke, headache, multiple sclerosis, dementia, movement disorders, and neuromuscular disorders), there was no lack of intriguing, novel approaches to the pathogenesis, diagnosis, and treatment of neurological disorders. As always, on the following pages we have compiled some of the abstracts we were most impressed by, two of which discuss Charcot-Marie-Tooth disease, an inherited disorder that involves the peripheral nerves, and therapeutic potential along with a new highly sensitive technology that can be used to monitor disease progression.
Highlighting the importance of the influence of inflammation on neurological disorders, the overarching theme of this this year’s congress was ‘Neuroinflammation – Science. Synergies. Solutions.’. Many sessions on offer at the congress touched on the potential involvement of neuroinflammation in diseases such as epilepsy, stroke, metabolic encephalopathy, Parkinson’s disease, migraine, and more. This theme depicts thinking outside of the box by exploring pathways that were previously believed to not be involved, setting a precedent for the rest of the congress.
One of the most important aspects of congresses like EAN is the opportunity to discuss and debate controversial topics within the field. A perfect example of such communication was presented in the form of controversy sessions, in which the cases for and against the existence of chronic lyme disease, overuse of headache medication, pathogenesis of fibromyalgia, plus more, were disputed, all in an attempt to clarify discrepancies in each topic. In one’s daily schedule, such valuable opportunities are few; therefore, by critically overviewing the current status and most recent advances, and allowing opinions to be formed, these EAN sessions further our understanding of science and clinical care immensely.
Complementary to these controversial sessions was a special session entitled ‘Cannabinoids: between neuroinflammation and neurodegeneration’. Not only did this session educate audience members of the main characteristics of the endocannabinoid system, but also how the important mediators have fundamental functions within neuroinflammation and neurodegeneration. Special mention was given to the therapeutic potential cannabinoids possess for the reduction of seizure frequency and intensity in epileptic patients. Balancing the apparently positive benefits surrounding the use of cannabidiol, the possibility of abuse was also discussed.
EAN 2019 proved, once again, to be a congress where thought-provoking discussions take place, so much so that we are already looking forward to EAN 2020, which will be held in the beautiful city of Paris, France. Until then, we hope you enjoy reading our review of this year’s congress highlights.
Multiple Sclerosis Incidence Linked to Cancer Susceptibility
MULTIPLE sclerosis (MS) is a chronic condition that severely affects the brain, spinal cord, and optic nerves, and is one the most common neurological conditions to manifest in young adults; however, there has been little research conducted into determining cancer risk in this demographic. Emerging results from a 65-year follow-up analysis of approximately 7,000 Norwegian MS patients has shown that a higher cancer susceptibility exists in this patient population, especially malignancies of the central nervous system, respiratory system, and urinary tract. These findings were presented as part of a press release at this year’s EAN Congress in Oslo, Norway.
Included within the study were 6,883 MS patients born between 1930 and 1979 who were registered with numerous Norwegian cancer and MS registries and prevalence studies. For control purposes, 8,918 siblings without MS were studied, as well as 37,919 non-MS individuals. In the MS cohort, increases in cancer prevalence were apparent: respiratory cancer (66% increase), central nervous system cancer (52% increase), urinary cancer (51% increase), and overall cancer (14% increase). Additionally, the unaffected sibling group displayed increased propensity for haematological cancers compared to their MS-afflicted siblings and the general population.
Dr Nina Grytten, lead researcher of the study from Haukeland University Hospital, Bergen, Norway, commented on the link between MS patients and their un-affected siblings saying that “the risk assessment between these two groups is extremely interesting because they share the same genetics and environmental conditions.”
Whilst a significant association has been revealed in this study, the authors emphasise the need for further research to uncover the precise mechanisms by which this association presents. Developing a better understanding could lead to quicker cancer diagnoses for these patients and positively impact on clinical outcomes and survival.
One in Ten People Report Having had ‘Near-Death’ Experiences
FINDINGS have emerged from this year’s EAN Congress attesting that mystical near-death experiences (NDE), in which people claim experiencing spiritual and physical symptoms such as out-of-body sensations and time distortion, affect an estimated 10% of the general population. These events occur to an equal degree in people who are not in imminent danger as to those who are, for instance in car crashes or combat situations.
In the study of 1,034 subjects from across 35 countries recruited through an online crowdsourcing platform, those who answered ‘yes’ to the question to whether having or not experienced an NDE proceeded to describe the perceptions they had using an assessment tool called the Greyson Near-Death Experience Scale. These included abnormal time perception (87%), enhanced speed of thought (65%), vivid senses (63%), and feeling separated from one’s body (53%).
Of the 289 people who reported experiencing an NDE, 106 reached a threshold of 7 on the Greyson NDE Scale and thus confirmed having had a true NDE. Of the subjects who claimed experiencing an NDE, the majority (73%) perceived their experience as being unpleasant; however, when these figures are adjusted for Greyson threshold the degree of enjoyment actually increased (53% when a threshold of 7 was reached).
An additional association was made between NDE occurrence and rapid eye movement (REM) sleep intrusion into wakefulness. The latter, characterised by symptoms such as visual and auditory hallucinations and sleep paralysis, was more common in people with scores ≥7 (47%) compared to those with scores ≤6 (26%).
“Although association is not causality, identifying the physiological mechanisms behind REM sleep intrusion into wakefulness might advance our understanding of near-death experiences,” explained lead researcher Dr Daniel Kondziella form the University of Copenhagen, Denmark.
Finding the Time and Space to Combat Alzheimer’s
SPACE and time mechanisms in the brain require greater levels of understanding to successfully combat Alzheimer’s disease, according to Prof Edvard Moser, Kavli Institute for Systems Neuroscience, Trondheim, Norway, during EAN 2019. The Nobel Laureate explained how the inability to keep track of time, recall memories, and finding one’s way serve as the first indications of Alzheimer’s development.
“The neural networks that generate space and time are the very first cells that start to die, perhaps decades before we notice clear symptoms of Alzheimer’s disease,” commented Prof Moser. “The discoveries of how the brain encodes space, time, and memory is crucial to understanding how higher mental function is generated and of great importance to clinical neuroscience and the global efforts to fight brain disease.”
Prof Moser was joint recipient of the Nobel prize for Physiology or Medicine in 2014 for the breakthrough discovery of a positioning system in the brain. At EAN 2019, he outlined the importance of establishing the existence of grid cells in 2005, which led to this award; these cells cover a person’s spatial environment by generating regular hexagonal patterns, providing information on distances and directions.
Other research has revealed the presence of several types of navigation cells in the brain, each with their own distinct function, enabling an alternative way for people to find their way, for example in the hippocampus and medial entorhinal cortex regions. There are also so-called ‘speedometer’ cells, which gauge the speed of travel as well as head direction cells, alerting someone when they are close to the edge of something by setting off neural alarms.
Ultimately, it is building upon current insights into time-tracking and space-mapping neural systems that hold the key to tackling Alzheimer’s disease, according to Prof Moser. He added: “The brain has specialised neural systems for encoding space, time, and memory that we are now starting to uncover. The next exciting steps are to understand how hundreds, or thousands of neurons interact, in order to create the sense of space or time.”
Study Reveals the Impact of the Holocaust on Brain Structure
HOLOCAUST survivors are afflicted with life-long effects on their brain function, with significantly lower volumes of grey matter in their brains compared with the general population, a study presented at EAN 2019 has shown. The authors displayed early evidence that the brain structures of the survivors’ children and grandchildren are also negatively impacted. The findings are expected to spark greater efforts into learning how severe trauma impacts brain function in the long term, helping the creation of therapy strategies to support such people.
Prof Ivan Rektor, Masaryk University, Brno, Czech Republic, commented: “After more than 70 years, the impact of surviving the Holocaust on brain function is significant. We revealed substantial differences in the brain structures involved in the processing of emotion, memory, and social cognition, in higher levels of stress but also of post-traumatic growth between Holocaust survivors and controls. Early results show this is also the case in children of survivors too.”
In the study, the volume of grey matter in areas of the brain responsible for stress response, memory, motivation, emotion, learning, and behaviour in 28 Holocaust survivors were revealed by MRI scanning to be significantly lower than that of 28 controls who do not have a personal or family history of the Holocaust. The average age of the participants was 79–80 years.
The team then compared the scan results of survivors above and below the age of 12 years in 1945. The younger survivors had significantly more expressed grey matter reduction, indicative of how a brain still developing in childhood is particularly vulnerable to a stressful environment. They also discovered there was a reduced volume of grey matter in parts of the brain associated with post-traumatic stress disorder (PTSD) in combat veterans and people who had experienced early life stress, aligning with earlier studies. However, grey matter reductions in other areas of the brain in the Holocaust survivors was far higher than observed in people with PTSD.
Prof Rektor added: “Our hope is that these findings and our ongoing research will allow us to understand more about the effect of these experiences in order to focus therapy to support survivors’ and their descendants’ resilience and growth. We may also reveal strategies that Holocaust survivors used to cope with trauma during their later lives and to pass on their experience to further generations.”
Earlier Intervention is Pivotal for the Successful Treatment of Alzheimer’s Disease
ILLUMINATING aspects of the mechanism of Alzheimer’s disease, hereditary forms and results from failed clinical trials can progress our understanding of this perplexing disease. During the prestigious ‘Brain Prize Lecture’ at EAN 2019, Prof Bart De Strooper, Director of the UK Dementia Research Institute, London, UK, and Group Leader at the VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium, presented data from decades of Alzheimer’s and genetic studies, outlining the need for early intervention to protect people against Alzheimer’s symptoms later in life.
Prof De Strooper has contributed significantly to the characterisation of the pathogenesis of Alzheimer’s disease. Notably, the discovery that abnormal amyloid plaques in the brains of Alzheimer’s patients can be a result of mutations in presenilin: a section of the y-secretase enzyme that breaks down β-amyloid chains. The production of these amyloid-β plaques is thought to initiate a neurodegenerative process, thus understanding how these mutations drive Alzheimer’s will help the development of new treatments.
Despite this knowledge, attempts to target the pathway with therapeutics have been unsuccessful. Acknowledging the possibility that current interventions are given at the latter stages of the disease, when symptoms are already present, Prof De Strooper commented: “scientists need to shift their focus to the earlier stage of the disease and think about the cellular environment in which the disease develops…”. He added: “treating amyloid at a very early stage could protect against symptoms later on and we must target these processes if we want to make the most effective treatments.”
Furthermore, Prof De Strooper argued that potential therapeutics have been tested in patients with a too advanced disease stage, therefore it is difficult to alter the disease progression. Looking to the future, intervening in the earlier stages of disease and altering the progression of disease seems to be a potential therapeutic option in treating Alzheimer’s disease.
Reducing Mortality and Stroke Risk with Statins in Dementia Patients
THE IMPORTANCE of investigating stroke in dementia patients is highlighted by the fact that the risk of stroke is three times higher in patients with mild dementia and seven times more likely in patients with severe dementia. With an expectation that those affected by dementia in Europe to double to 20 million by 2030, research into mortality in dementia patients needs to be investigated. Results from a large cohort study into statins and the risk of stroke were presented at EAN 2019, Oslo, Norway, on the 1st July.
The study included 44,920 dementia patients from the Swedish Dementia Registry between 2008 and 2015. Results identified that patients who used statins had a 22% lower risk of all-cause death and a 23% lower risk of stroke. A protective effect on survival with statins was observed: a reduction in mortality rate was seen in those <75 years of age (27%) and in older patients (20%). Interestingly, differences in mortality with statin use were seen between men and women, with reductions observed in 26% and 17% of patients, respectively.
“Survival in patients in dementia is variable, and previous studies have identified many factors associated with survival and risk of stroke in these patients,” commented first author Dr Bojana Petek from the University Medical Center Ljubljana, Ljubljana, Slovenia, and the Karolinska Institutet, Solna, Sweden. “However, the effect of statins on these two outcomes is not clear. The aim of this study was to analyse the association between the use of statins on the risk of death and stroke in patients diagnosed with dementia.”
The authors explained that because the study is a cohort study and does not have a structure similar to clinical trials, only associations between statins can mortality could be identified, of which could not be definitively proved. Despite this, the results are encouraging and could provide the rationale for including statins in the treatment plan of dementia patients.
Norway Introduces First European Brain Health Strategy
BRAIN disease strategies for prevention and management were presented at EAN, on the 1st July 2019 in Oslo, Norway. The Norwegian Brain Health Strategy 2018–2024 was presented by Prof Anne Hege Aamodt, President of the Norwegian Neurological Association at the congress, outlining Norway’s approach to brain diseases and their health strategy.
The initiative has four aims: 1) to provide good, lifelong brain health along with prevention and better quality of life; 2) to provide user-centred care and relative support; 3) to offer holistic care from a range of multi-disciplinary teams; and 4) to ensure adequate knowledge is available through more research and innovation.
Brain disease accounts for roughly 10% of the global disease burden, with one of the most common, dementia, affecting 50 million people across the world. This number is increasing; by 2030 the number of people living with dementia is expected to rise to 82 million, and by 2050, this could reach 152 million. Prof Aamodt said: “Brain diseases affect a wide range of people in all stages of life and, as people are living for longer, greater numbers now live with a range of brain diseases.”
“Prevention of brain diseases, the provision of equal treatment, follow-up, and rehabilitation, as well as increased research and expertise, is absolutely vital in providing patients with optimal outcomes. This strategy will help to facilitate this for a number of brain diseases, including dementia, multiple sclerosis, Parkinson’s, and stroke-related conditions,” continued Prof Aamodt.
The initiatives outlined are underway, including a €20 million investment from a National Clinical Research Centre to work towards a clinical treatment of brain diseases, including multiple sclerosis, dementia, and amyotrophic lateral sclerosis. The Norwegian Research Council are also set to receive €5 million for the improvement of research and innovation across neurological conditions.
Prof Aamodt concluded: “We believe that this national strategy should be replicated and implemented across Europe, tailored for each country. The continent will undergo major societal transformations, such as the ageing population, that will impact on brain diseases and health services must adapt to these changes.”
Infant Language Impairment Associated with Epilepsy Drugs in Pregnancy
EPILEPSY medication taken during pregnancy could increase the risk of language impairment in children aged 5 and 8 years. The research, presented at EAN on the 2nd July 2019 in Oslo, Norway, included an investigation into sodium valproate and carbamazepine. Results also showed that folic acid supplements taken during pregnancy had a protective nature against language impairment for children.
The study looked at two antiepileptic drugs (AED): sodium valproate, an AED that is used only in situations where there is no alternative for pregnant patients as there are known risks for unborn babies associated with the drug; and carbamazepine, which had been considered a safer alternative.
Children of mothers both with and without epilepsy, who had enrolled in the Norwegian Mother and Child cohort study from 1999–2008 were studied. Information was provided including epilepsy diagnosis, AED used in pregnancy, and the child’s verbal ability at 5 and 8 years of age. Questionnaires were used to gather the information and validated using language screening tools. The concentration of AED in the blood was measured using blood samples taken at Weeks 17–19 of gestation and umbilical cord samples following birth.
AED-exposed children were found to have language impairment adjusted odds ratios of 1.6 at 5 years of age and 2.0 at 8 years of age when compared with children with non-epileptic mothers. Exposure to carbamazepine monotherapy showed a significantly increased risk of language delay in children when compared with the control group at 8 years. There was a correlation between higher maternal plasma valproate levels and language delay at 5 years. Mothers who took periconceptual folic acid as a supplement during pregnancy had children who were at lower risk of AED-associated impairment in both age groups.
Lead research, Dr Elisabeth Synnøve Nilsen Husebye, University of Bergen, Bergen, Norway, discussed the findings: “The main findings of the research are that fetal antiepileptic drug exposure is associated with an increased risk of language impairment in children of mothers with epilepsy, at age 5 and 8 years, especially after exposure to carbamazepine and valproate.” She recognised the need for further research on new AED, such as lamotrigine, levetiracetam, and tompiramate.