Abstract
The 21st Meeting of the European Neurological Society (ENS) was held on 28–31 May 2011 in Lisbon, Portugal. Over 3400 participants attained the meeting. The ENS meeting is an international event, which offers an exclusive opportunity for excellent continuous education, as well as an update of cutting-edge research in all fields of neurology. Among the key themes of this year’s conference, the contribution of magnetic resonance-based techniques to unravel the physiopathology of neurological diseases and improve our knowledge of the way they progress was highlighted in several sessions. This article summarizes the major neuroimaging findings of the 21st ENS Meeting.
In May 2011, the 21st Meeting of the European Neurological Society (ENS), chaired by José M Ferro (Hospital of Santa Maria, Lisbon, Portugal), was held in Lisbon (Portugal). The ENS meetings offer an exclusive opportunity for excellent continuous education in all fields of neurology, both for practising neurologists and for young neurologists in training. ENS meetings also represent an international stage where people devoted to clinical or translational research can present and discuss the results of their work in an open and friendly, but testing environment. ENS congresses are held every year (the next one is planned to be held in Prague from 9 to 12 June 2012). In Lisbon, the ENS meeting attained the highest number of participants ever recorded at an Annual Meeting of the Society. Neurology experts (3428) from around the world discussed the latest developments in all areas of neurology. The scientific program included five symposia, 18 teaching courses, nine workshops, several interactive case presentations and practical sessions in clinical neurophysiology, together with oral communications and several hundred posters.
Among the key themes of this year’s conference, the contribution of magnetic resonance (MR)-based techniques to unravel the physiopathology of neurological diseases and improve our knowledge of their evolution was been highlighted. The exciting opportunities that MRI techniques offer clinical neurology were elegantly illustrated by the speakers of the Teaching Course organized by Massimo Filippi (University of Milan, Milan, Italy) and cochaired by Jean-Claude Baron (University of Cambridge, Cambridge, UK), entitled ‘MRI for early diagnosis and identification of predictors of early clinical evolution’.
This article summarizes the major neuroimaging findings related to different neurological diseases, including multiple sclerosis (MS), headache and neurodegenerative diseases, presented in several sessions of the 21st ENS Meeting.
Multiple sclerosis
From its first introduction in the clinical arena, MRI appeared as a valuable tool to investigate MS. This is mainly owing to its high sensitivity for detecting focal abnormalities in the CNS of these patients, as well as to its ability to assess the presence of damage to the so-called ‘normal-appearing’ brain tissues. Several speakers outlined that MR measures could contribute to characterizing the heterogeneous clinical phenotypes of MS and to help define their pathophysiology Citation[1]. For instance, it has been shown that, compared with patients with relapsing MS, those with a progressive disease phenotype have different patterns of microglia activation in T1 hypointense lesions (termed black holes). New analysis methods are allowing regional disease-related changes to be tracked and are resulting in an increased correlation between MRI and clinical deficits. In relapsing–remitting (RR) MS patients, diffusion tensor (DT) MRI, which interrogates the microstructure of the brain white matter (WM) in vivo by measuring directional changes in water diffusivity, is allowing the intrinsic damage to specific WM tracts to be characterized, as well as the relationship of this damage with physical disability and cognitive impairment. WM microstructural abnormalities, although occurring in virtually all MS patients, have different topographical patterns in the various disease phenotypes. Interestingly, while the supratentorial brain harbors abnormalities in all the disease groups, the involvement of the infratentorial regions differs markedly among the clinical phenotypes, being spared in primary progressive MS and benign MS and heterogeneously damaged in RRMS and secondary progressive MS. In addition, RRMS patients showed a prominent involvement of anterior gray matter (GM) regions and posterior WM areas, thus suggesting distinct patterns of GM and WM regional damage distribution in these patients. Finally, using cervical cord functional MRI, an over-recruitment of the cervical cord during a tactile stimulation was found in patients with progressive MS, which is greater in secondary progressive MS than in primary progressive MS.
The effort spent during the past three decades to explore the many potentialities of neuroimaging techniques in MS patients has led to the identification of MRI markers to monitor the evolution of the disease, both in clinical practice and in the context of disease-modifying treatment trials. An intriguing finding presented at the meeting is that the longitudinal change of spinal cord volume, which has been previously shown to be an important indicator for disease evolution and treatment response, can now be readily measured using a new semiautomatic segmentation method Citation[2]. The demonstration of stability of such a measure among different centers Citation[3] supports its use as a surrogate marker to monitor disease progression in multicenter trials.
Headache & migraine
Several metabolic Citation[4,5] and functional imaging studies Citation[6] have indicated that a primary hypothalamic dysfunction might be involved in the pathogenesis of cluster headache. However, there are data supporting a more global CNS dysfunction in cluster headache patients, similar to what has been described in migraine patients Citation[7] and in patients suffering from chronic pain conditions Citation[8]. A study in the session on ‘Neuropathic pain and primary headache’ investigated the pattern of regional brain abnormalities in patients with cluster headache and showed that these patients experience tissue loss of GM regions that are part of the antinociceptive system, which is shared with other chronic pain conditions. Longitudinal studies are now warranted to define whether these GM abnormalities vary in the different stages of the disease (e.g., acute vs chronic phase) and whether they reverse after the institution of treatment. A second study used functional MRI and visual optokinetic stimulation in a group of vestibular migraine patients, which is the second most frequent form of central vertigo syndromes, and demonstrated that patients with vestibular migraine have a dysfunctional intracortical inhibition.
Neurodegenerative diseases
The clinical and pathological heterogeneity of neurodegenerative disorders poses a significant diagnostic challenge and the in vivo phenotypic characterization of these patients can be improved by supplementing the clinical evaluation with imaging biomarkers Citation[9–12], as highlighted by several reports at this meeting. A widespread pattern of cortical thinning is present in patients with amyotrophic lateral sclerosis (ALS). In particular, a regional atrophy analysis revealed a subtle GM tissue loss in regions located in the frontal, temporal and parietal lobes in these patients, thus suggesting that measuring cortical thickness is a very promising venue to gain additional insights into disease-related pathological changes of ALS, especially those associated with cognitive deficits. Another study investigated whether a specific pattern of GM tissue loss is associated with freezing of gait (FOG) in patients with Parkinson’s disease (PD). GM frontal and parietal atrophy occurs in PD patients with FOG, thus suggesting that FOG in PD seems to share a common pattern of structural damage to the frontal and parietal cortices with executive dysfunction and perception deficits.
Another intriguing finding was the demonstration that WM alterations are among the major pathological features of normal aging Citation[13] and neurodegenerative conditions, including Alzheimer’s disease and allied conditions Citation[14], frontotemporal lobar degeneration spectrum disorders Citation[15] and PD Citation[16]. Importantly, age-related decline in memory performance was shown to be mediated by changes in fornix microstructure. A combined structural and DT MRI tractography approach was used to assess the long-range ventral and dorsal WM pathways in patients with posterior cortical atrophy, showing that the patterns of WM abnormalities in these patients closely mirror the clinical and cognitive phenotypes of this syndrome. Patients with the behavioral variant frontotemporal dementia showed widespread DT MRI abnormalities affecting most of the WM, bilaterally. In primary progressive aphasia patients, WM damage was more focal and varied across the three variants: left fronto–temporo–parietal in nonfluent; left frontotemporal in semantic; and left frontoparietal in logopenic patients. In each frontotemporal lobar degeneration syndrome, strong and anatomically congruent correlations between WM changes and regional GM atrophy were found. However, DT MRI alterations were also identified in WM that were not directly linked to atrophied GM regions. In addition, WM tract degeneration turned out to be associated with neuropsychological deficits in ALS patients. In PD patients, microstructural damage to cerebral WM tracts occur with increasing disease severity, and the involvement of WM tracts was found to be related to the accumulation of both motor and cognitive deficits. Furthermore, a study showed that mild cognitive impairment in PD patients is associated with an intrinsic structural damage to the major WM interhemispheric and cortico–cortical pathways. Taken together, all of these findings suggest that DT MRI has the potential to provide reliable antemortem markers of tissue damage in neurodegenerative disorders and may contribute to improving our understanding of the development of cognitive and motor dysfunctions in these conditions.
Conclusion
We believe that the findings presented at the ENS meeting in Lisbon and briefly summarized here provide critical pieces of information that are likely to improve our in vivo understanding of the pathological mechanisms associated with the major CNS demyelinating and degenerative diseases, with the potential to radically modify the way we approach and treat individuals with neurological diseases. Abstracts of the meeting are published in the society’s journal, Journal of Neurology.
Financial & competing interests disclosure
Federica Agosta has received funding for travel from Teva Pharmaceutical Industries Ltd, and has received speaker honoraria from Bayer Schering Pharma, Sanofi Aventis and Serono Symposia International Foundation.
Massimo Filippi serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd and Genmab A/S; has received funding for travel from Bayer Schering Pharma, Biogen-Dompè, Genmab A/S, Merck Serono and Teva Pharmaceutical Industries Ltd; serves as a consultant to Bayer Schering Pharma, Biogen-Dompè, Genmab A/S, Merck Serono, Pepgen Corporation and Teva Pharmaceutical Industries Ltd; serves on speakers’ bureaus for Bayer Schering Pharma, Biogen-Dompè, Genmab A/S, Merck Serono and Teva Pharmaceutical Industries Ltd; receives research support from Bayer Schering Pharma, Biogen-Dompè, Genmab A/S, Merck Serono, Teva Pharmaceutical Industries Ltd and Fondazione Italiana Sclerosi Multipla; and serves on editorial boards of the American Journal of Neuroradiology, BMC Musculoskeletal Disorders, Clinical Neurology and Neurosurgery, Erciyes Medical Journal, Journal of Neuroimaging, Journal of Neurovirology, Magnetic Resonance Imaging, Multiple Sclerosis, Neurological Sciences and Lancet Neurology.
Federica Agosta received partial reimbursement for attendance at the meeting from the ENS and the Serono Symposia International Foundation. Professor Filippi is a member of the ENS Executive Board and Teaching Course Director. He received reimbursement for attendance at the meeting. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
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