Originally due to take place in Paris, France, the 6^th Congress of the European Academy of Neurology (EAN) was held virtually - for the first time in its history - as a result of the COVID-19 pandemic.

Professor Claudio Bassetti, Acting President of the EAN

Multiple Sclerosis

Practical Guidelines to Assess MRI Lesions that are Typical or Atypical for MS

The goal of this case-based workshop was to reinforce the correct recognition of MS lesions included in 2017 McDonald diagnostic criteria, focusing on both typical magnetic resonance imaging (MRI) features and “red flags” suggestive of an alternative diagnosis.

Typical MS lesions were reviewed by Celine Louapre, Paris, France, who used two clinical case studies and multiple MRI images to illustrate the characteristic periventricular, cortical/juxtacortical, infratentorial and spinal cord lesions associated with MS. She reminded delegates that MS enacts multifocal and chronic neurological damage which is typified by both dissemination in space (DIS) and dissemination in time (DIT). MRI remains ‘the’ tool for diagnosing MS, said Dr Loupare, and offers excellent sensitivity assuming clinicians have the experience to recognise MS-type lesions correctly. Sensitivity can be boosted by increasing the resolution (to 3T or 7T) or improving the sequences, for example, using short T1 inversion recovery (STIR) for imaging the spinal cord and double inversion recovery (DIR) for cortical lesions. 

Key changes to the 2017 McDonald criteria for DIS and DIT

Using clinical cases as examples, Christian Enzinger, Graz, Austria, outlined practical guidelines for the assessment of typical and atypical MS lesions, including how to distinguish MS from other key demyelinating disorders. 

Dr Enzinger emphasised that MRI scans must always be interpreted in the appropriate clinical context and grounded in the basic knowledge of what constitutes a lesion. The integration of history, examination, MRI and laboratory evidence by a clinician with MS-related expertise remains fundamental to the reliable diagnosis of MS or alternative conditions. In cases with lingering uncertainty, the threshold for carrying out additional tests should be low, said Dr Enzinger, and should include spinal cord MRI and/or cerebrospinal fluid (CSF) examination.

Cristina Granziera, Basel, Switzerland, gave a masterclass on how to decipher “red flags” suggestive of central nervous system (CNS) vasculitis and other inflammatory disorders. Dr Granziera highlighted the MIMICS algorithm as a key tool for identifying atypical MS lesions in everyday clinical practice. The central vein sign and iron rims can also provide potentially valuable clues in the differential diagnosis of MS, particularly in distinguishing from other CNS inflammatory vasculopathies.

DIS, dissemination in space; NMOSD, neuromyelitis optica spectrum disorder

Differential diagnosis of MS using the MIMICS algorithm

Promoting Structural Repair and Functional Recovery in MS

Promoting CNS remyelination and neuroprotection are critical to the prevention of disability progression in MS. This symposium explored underlying mechanisms of myelin repair and evolving therapeutic strategies aimed at stimulating remyelination/neuroprotection. 

The pathophysiological basis of functional recovery was discussed by Diego Centonze, Rome, Italy, who summarised existing data supporting the role of synaptic plasticity changes in the clinical compensation for structural damage in MS. He explained that clinical disability in MS appears when the long-term potentiation (LTP) reserve of surviving neurons is exhausted, and that rehabilitation exerts its clinical benefits by preserving or boosting these reserves. LTP requires the activation of a range of substances - N-methyl-D-aspartate, cannabinoids, dopamine and neurotrophins - raising the possibility that pharmacological interventions which stimulate these target receptors could enhance the effects of rehabilitation by favouring synaptic plasticity. LTP can also be impaired by acute inflammation which may further explain the beneficial impact of disease-modifying drug (DMDs) therapy in MS.

DWI, diffusion-weighted imaging; DW-MRS, diffusion-weighted magnetic resonance spectroscopy; NAA-HMRS, N-acetylaspartate H-magnetic resonance spectroscopy; MRI, magnetic resonance imaging.

Advantages and disadvantages of neuroimaging techniques

Ongoing and future therapeutic strategies

Gianvito Martino, Milan, Italy, delivered a cutting-edge talk on the use of neural stem cell therapy in MS. Dr Martino explained how transplanted stem cells work through a combination of both direct cell replacement and the bystander effect. They exert their neuroprotective effects by secreting trophic factors and immunomodulatory molecules that foster endogenous precursors to promote remyelination and to rescue damaged axons and neurons. Depending on the tissue microenvironment, transplanted neural precursor cells (NPCs) appear able to recapitulate the ‘physiological’ non-neurogenic homeostatic and neurogenic functions produced by endogenous NPCs. The bench-to-bedside translation of NPC transplants has already begun in MS, revealed Dr Martino, and appears safe in the first nine patients to have completed 2 years of follow-up, with no reported side-effects. Importantly, the bystander effect was measurable in the CSF as early as 3 months post-transplantation.  

Multiple sclerosis, differential diagnosis
Neuro-Ophthalmological Mimickers

This case-based workshop was designed to support knowledge and practice in the differential diagnosis and management of three neuro-ophthalmological conditions that commonly present to the neurologist such as MS-related acute optic neuritis.

Mimickers of MS-related acute optic neuritis were addressed by João Lemos, Coimbra, Portugal. Dr Lemos reviewed six real-world case studies, highlighting important “red flag” signs and symptoms suggestive of alternative diagnoses. Dr Lemos cautioned clinicians not to suspect MS-related optic neuritis if a patient’s history includes preceding febrile illness, absence of periocular pain, the presence of photopsias or metamorphopsia, bilateral simultaneous presentation, no improvement or severe visual loss after 3 weeks, or steroid dependency. He also highlighted key clinical clues to be alert for during examination and work-up of the patient.

Atypical features observed in an examination of MS-related optic neuritis

Atypical features observed in an examination of MS-related optic neuritis

• Extensive optic nerve enhancement or a severe loss of nerve fibre layer on optical coherence tomography (OCT), particularly if this doesn’t fit the pattern of temporal loss in MS
• The presence of subretinal fluid
• Retinal pigment epithelium disruption 

All of these features should make you think of an alternative diagnosis, Dr Lemos concluded. 

Multiple sclerosis
Pregnancy in Neurological Disorders

This teaching course addressed the myriad questions and issues that can arise when pregnancy occurs or becomes desirable in women with neurological disorders. Letizia Leocani, Milan, Italy, spoke about pregnancy in MS, a particularly pertinent topic given that the disease predominantly affects women of child-bearing age. Dr Leocani insisted that an MS diagnosis does not preclude pregnancy and that pregnancy should not be discouraged a priori.
However, it is important to discuss family planning early in the clinical journey and have a clear action plan for each step in advance - from pre-conception, through pregnancy and into the postpartum period. For patients with active disease already receiving DMD treatment, alemtuzumab or cladribine can be considered before pregnancy or natalizumab given during pregnancy (up to 30 weeks gestation). For the treatment of relapses during pregnancy, methylprednisolone IV is recommended and any neuroimaging should always be carried out without gadolinium. Glatiramer acetate, interferon-β and natalizumab are all suitable options for use during breastfeeding, said Dr Leocani.

When should natalizumab be stopped and restarted in patients with MS planning pregnancy?

How to Handle Safety Issues in MS Treatment

The dual issues of infections and vaccinations were tackled by Lucia Moiola, Milan, Italy. Dr Moiola underscored the importance of prevention versus treatment, both for reducing infectious morbidity and mortality and avoiding interruptions to DMD therapy. Clinicians should also be equipped with an in-depth knowledge of drugs’ mode/duration of action to facilitate recognition of key infection-related adverse events and practice active pharmacovigilance. Strategies for prevention include: infection identity cards, vaccine cards and treatment of active infections. Dr Moiola stressed that vaccination is essential in MS and the timing and schedule should be tailored on an individual basis according to specific risk factors such as travel, sexual habits and employment. 

Autonomic Nervous System Dysfunction In MS
Highlight Session

This symposium on the final day of EAN 2020 shone a spotlight on key developments and state of-the-art developments in the field of autonomic disorders.

Mario Habek, Zagreb, Croatia, explored the clinical implications of autonomic nervous system (ANS) dysfunction in MS, with a focus on the MS prodrome, ANS symptoms and ANS testing in MS. Dr Habek described the specific pattern of autonomic abnormalities in MS, where disease activity measured by relapses or new T2 lesions affects sympathetic parts of the ANS. In contrast, disease progression, which is the consequence of neurodegeneration, is connected to abnormalities in the parasympathetic nervous system. Dr Habek also outlined how ANS dysfunction evolves over the time course of the disease, with initial ANS symptoms appearing up to 10 years prior to MS diagnosis and accumulating increasingly as the disease advances. T2 lesion load, in particular, appears to be a key predictor of worsening composite autonomic severity score. 

ANS symptoms in the MS prodrome

ANS symptoms in the MS prodrome

Director of the German Aerospace Centre - Jens Jordan, Cologne, Germany - gave an intriguing presentation on the relevance of autonomic space medicine to daily clinical neurology, applying lessons learnt in astronauts to patients on earth. One of the key insights gained from studying astronauts is how the ANS adapts in order to maintain physiology. Orthostatic symptoms result from the interaction of the nervous system and other mechanisms, with volume regulation proving particularly important. The ability to stand and maintain blood pressure can also be lost; ‘use it or lose it’, Dr Jordan warned. 

Gregor Wenning, Innsbruck, Austria, discussed developments in DMDs for multiple systematrophy (MSA), a progressive neurological disorder which has some overlapping clinical signs and symptoms with MS. Dr Wenning gave an overview of the large number of DMD candidates currently in the clinical pipeline. Broadly speaking, there are two key targets for DMDs in MSA: reduction of α-synuclein deposits and inhibition of neuroinflammation/microglial activation. Although a number of Phase 3 therapeutic trials have already beencompleted with agents such as rifampicin, riluzole (indicated for amyotrophic lateralsclerosis) and minocycline, results were predominantly negative. Looking ahead, Dr Wenning highlighted the iron chelator PBT434 and the α-synuclein oligomerisation inhibitoranle138b as the most promising of the current early-stage drugs while, among the moreclinically advanced candidates, positive results have been attained with mesenchymal stemcells and epigallocatechin gallate.

Alzheimer’s Disease and Dementia

Neuroimaging in Dementia: News and Perspectives

Structural and functional neuroimaging biomarkers play a key role in the clinical diagnosis of diseases that cause cognitive impairment. This focused workshop session explored new approaches - based on the stalwarts of MRI and PET - which are being explored for the neuroimaging of dementing disorders.

Massimo Filippi, Milan, Italy, reviewed new and established MRI tools in cognitive disorders, looking at what is consolidated, nearly consolidated and new in the field. 

What is consolidated and new in MRI?

What is consolidated and new in neuroimaging in patients with dementia?

Structural MRI is mandatory to exclude the presence of secondary causes and also helps clinicians visualise the topography of atrophy, which can shed light on the underlying neurodegenerative aetiology. Dr Filippi stressed that MRI is ‘more than hippocampal volume’, with strong utility in the differential diagnosis of Alzheimer’s disease (AD) versus non-AD dementia and also a useful prognostic indicator in mild cognitive impairment (MCI). Advanced techniques are already able to measure white matter and resting state functional MRI (fMRI) changes. Looking to the future, higher resolution imaging such as 7T will allow for increasingly detailed, cortical layer-specific analysis of microcircuits implicated in the earliest stages of disease. 

The impact of amyloid and tau PET in the diagnosis and prognosis of neurodegenerative diseases was examined by Alexander Drzezga, Cologne, Germany. Amyloid PET is a clinically available method that may facilitate the very early diagnosis of amyloid pathology (although time to conversion in healthy participants without cognitive symptoms remains unclear), with additional prognostic value in MCI and subjective cognitive decline. Its differential diagnostic power covers detection of atypical AD and exclusion of pseudo-AD, but it is not yet a reliable tool for staging. Tau-PET - although still experimental - also offers a window into early diagnosis at the start of neurodegeneration, albeit with less sensitivity in the preclinical stages of disease. Diagnostically, it can discriminate between tau-negative versus tau-positive forms of dementia, with the deposition pattern a key delineating factor, and also shows value as a tool for staging and follow-up. Dr Drzezga advised that the ultimate choice between amyloid or tau-PET should depend on the diagnostic question, with a combination of the two biomarkers likely to prove most helpful with regards to ATN classification framework (A stands for β-amyloid [Aβ] pathology, T for tau pathology and N for other non-specific biomarkers of neurodegeneration).

Fluid and Structural Disease Biomarkers to Predict Neurodegenerative Diseases

This workshop session focused on the benefits of integrated translational and clinical research, showcasing a series of biomarkers that may enable the prediction of disease onset and preventive therapeutic intervention in neurodegenerative diseases. 

Mathias Junker, Tubingen, Germany, explored the possibility of bridging the translational gap using murine models of neurodegenerative diseases, which he described as ‘wonderful tools’ for predicting and understanding fluid changes in the clinical setting. Thanks to these murine studies, we now know that both CSF tau (and p-tau) levels are tightly correlated to Aβ aggregation, said Dr Junker. Neurofilament light (NFL) levels in both the CSF and blood also afford a reliable marker for neurodegeneration associated with proteopathic lesions in the brain. Remarkably, the rate of change in NFL levels has been shown to predict cortical thinning and cognitive changes up to 16 years before the expected onset of typical AD symptoms. 
 

CSF and blood-based disease, treatment response biomarkers in AD and other neurodegenerative disorders were discussed by Charlotte Teunissen, Amsterdam, the Netherlands. She noted that biomarker panels are vital for the differential diagnosis of different dementias and there is an urgent need to develop new biomarkers, particularly for microglia and astrocytic activity. Ongoing research efforts in the biomarker arena include bPRIDE, a Europe-wide initiative using different multi-marker blood proteins panels for the early discrimination of dementias. Dr Teunissen explained that plasma panels of amyloid, p tau, NFL and glial fibrillary acidic protein can be robustly analysed using ultrasensitive technologies and are likely to be used across AD prescreening, diagnosis and therapy response monitoring in the near future. 

Federica Agosta, Milan, Italy, gave a talk covering structural and functional markers of neurodegeneration with applicability across both preclinical and clinical disease stages. She outlined the biomarker-based framework for AD which classifies imaging markers as either diagnostic or progression. In AD, imaging is very powerful for detecting progression markers of neuronal injury using tools such as fluorodeoxyglucose (FDG) PET, MRI and CSF t-tau, alongside newer modalities like diffusion tensor imaging (DTI) and resting-state fMRI. Moving forward, it may even prove possible to predict the network-dependent spread of pathology in neurodegenerative diseases, said Dr Agosta, with several studies now underway in this exciting area. 

Huntington's Disease

Differential Diagnosis and Therapy of Movement Disorders for General Neurologists

This teaching course set out to refresh neurologists’ knowledge of hyperkinetic movement disorders encountered in general practice such as Huntington’s disease, and bring neurologists up to speed with recent developments in the field.

Huntington’s disease currently ranks as the third most common inherited neurological disease

EAN President Prof Bassetti has pledged his hope for this meeting to return in physical form next year, with the 7^th Congress of the EAN scheduled to take place in Vienna from the June 19–22, 2021. However, with a commitment to continued innovation and a reduction in carbon footprint, key elements from this first ever virtual congress will be retained in 2021, including online presentations and livestream sessions providing accessibility to delegates from across the globe.

©Springer Healthcare 2020. This content has been independently selected and developed by Springer Healthcare and licensed by Roche for Medically. The topics covered are based on therapeutic areas specified by Roche. Inclusion or exclusion of any product does not imply its use is either advocated or rejected. Use of trade names is for product identification only and does not imply endorsement. Opinions expressed do not reflect the views of Springer Healthcare. Springer Healthcare assumes no responsibility for any injury or damage to persons or property arising out of, or related to, any use of the material or to any errors or omissions. Please consult the latest prescribing information from the manufacturer for any products mentioned in this material.