Plenary Sessions

Monday, November 2, 2015

Plenary Lecture 4 - Yahr Award Lecture , 08:30-09:00, Hall A​
New Concepts in Headache​, Jes Olesen, DK
Headache is, compared to its prevalence and socio-economic costs, the least funded of all neurological subjects. Nevertheless, impressive advances have been made over the last decade. The diagnosis has been improved by the advent of the second and the third edition of the International Classification of Headache Disorders. Diagnoses are now uniformly made throughout the world. The genetics of headache disorders is an advancing field. So far three genes have been identified in which mutations cause the rare monogenic familial hemiplegic migraine and in a huge meta-analysis using GWAS 38 independent loci have been associated with migraine without aura and migraine with typical aura. Environmental factors have been more difficult to document but low education, low socioeconomic status and hard physical exercise have been identified. The pathophysiology involves important messenger molecules such as nitric oxide, calcitonin gene-related peptide, pituitary adenylate cyclase activating peptide and, interestingly, hypoxia as encountered in high altitude . All provoke  migraine. New therapies have changed the field. Candesartan has appeared as a drug of choice for migraine prophylaxis and phase 2 studies have proven efficacy of antibodies against calcitonin gene-related peptide in migraine prophylaxis. Small molecule CGRP receptor antagonists have proven efficacious in acute attack treatment but none is currently in clinical development, possibly due to lever toxicity. Botulinum Toxin A has been registered as a prophylactic agent in chronic migraine.​Finally, an  international  definition  of  tertiary academic headache referral centers has been developed and such centers have proven their value in even the most difficult chronic headache patients.

Presidential Symposium, 09:00-10:45, Hall A​
DNA Aβ 42 Vaccination as Therapy to Prevent Alzheimer's Disease, Roger Rosenberg, US​​
DNA Aβ42 vaccination in which DNA encoding the Aβ42 peptide is injected is presented as  potential therapy to delay or prevent Alzheimer's disease. The injected DNA is translated in the immunized individual to produce Aβ peptide which then triggers  immune responses against the Aβ42 peptide. We are the first to show that DNA Abeta42 vaccination administered with the gene gun is highly effective to reduce Aβ42 levels in brain by 41% and the Aβ42-containing plaques by 50% in Alzheimer transgenic mouse models (Qu et al., 2004; 2006, 2007) which was confirmed later in studies by others. The immune response is Th2 ( IgG1) in the Alzheimer transgenic mouse and  IgG and IgA in New Zealand white rabbits. DNA Aβ42 vaccination  is non-inflammatory,  as  it induces a Th2 immune response (IgG1) and does not produce the pro-inflammatory factors: γ interferon and  Il-17 and does not induce proliferation of cytotoxic CD8 cells, all of which are induced in Aβ42 peptide vaccination, resulting in the stopping of a clinical trial. Our research describes the effectiveness, safety and potential therapeutic value of DNA Aβ42 vaccination in persons at risk for Alzheimer's disease (Rosenberg and Lambracht-Washington, 2015).​

Neurexins and Company: Towards a Molecular Logic of Neural Circuits, Thomas C. Südhof, US
Neurexins are presynaptic cell-adhesion molecules that bind to postsynaptic ligands to form trans-synaptic cell-adhesion complexes. Neurexins bind to multiple ligands, including neuroligins, LRRTMs, and the complex of cerebellins with GluRd2. The interactions of presynaptic neurexins with their postsynaptic ligands primarily function as signaling complexes that are essential for synapse function, and that shape the properties of synapses such as short- and long-term plasticity. Neurexins are encoded by three extraordinarily large genes, each of which generates longer a- and shorter b-isoforms that are in turn diversified into thousands of alternatively spliced transcripts. The various splice variants of neurexins and the various isoforms of their ligands exhibit strikingly different functional activities and binding affinities; their interactions are likely competitive, and contribute to determining the properties and nature of synapses. Although accumulating evidence demonstrates that neurexins and their ligands perform central functions in the assembly and function of neural circuits, but their precise roles and mechanisms of action are only now beginning to emerge. Moreover, although many mutations in neurexin and their ligands have been associated with autism, schizophrenia and other neuropsychiatric disorders, the mechanisms by which such mutations predispose to these devastating disorders are not understood. In my talk, I will describe our recent studies on how neurexins and their ligands shape synapse properties, and how dysfunction of neurexins and their ligands might predispose to neuropsychiatric disorders such as schizophrenia.

Tuesday, November 3, 2015

Plenary Lecture 6, 08:00-08:30, Hall A​
Cell therapy for CNS Disorders, Neil Scolding, UK
Multiple sclerosis (MS) is an incurable neurodegenerative disease representing a major cause of neurological disability, particularly affecting young adults. It is characterised by patches of damage throughout the brain and spinal cord, with loss of myelin and of myelinating cells (oligodendrocytes), and damage also to neurones and axons. Efforts to develop cell therapy for MS originally were built on the principle of directly implanting cells to replace oligodendrocytes and so regenerate myelin. Such efforts did not reach the stage of significant clinical translation; indeed, recent progress in our understanding of the complexity of MS disease processes introduces new and serious challenges to successful cell therapy, emphasising that it must achieve substantially more than 'just' the replacement of myelinating cells and remyelination. Cell implantation appears unlikely to be of value. The reasons include the observation that spontaneous myelin repair is far more widespread and successful than hitherto believed; the question of axon and neuronal loss, which correlates far more closely with progressive disability than does myelin loss; and the fact that damage occurs diffusely throughout the CNS and not just in discrete, isolated patches or lesions.  Meanwhile, however, parallel advances in dissecting the many and varied reparative properties of certain types of stem cell – including neuroprotective properties, interactions with resident/tissue-based stem cells, cell fusion and neurotrophin elaboration – offer renewed hope for developing cell-based treatments for MS. Significantly, these potentially beneficial properties may be of value not just in MS, but in other neurodegenerative diseases also: the advances outlined may well therefore suggest avenues for translating this approach not only to MS but also for other common (but equally incurable) neurological and neurodegenerative diseases.

Plenary Lecture 7, 08:30-09:00, Hall A​
Functional Disorders in Neurology: Changing a Negative to a Positive, Jon Stone, UK
Functional symptoms and disorders (also called psychogenic, non-organic and conversion disorders) are a common cause of distress and disability in the neurology clinic. In the last 10-15 advances in understanding, diagnosis and treatment of patients with functional disorders have changed the clinical landscape. These are turning traditionally negative views in to a more positive approach which brings these disorders back within standard neurological practice.​ In this lecture I will discuss: 1) The importance of making the diagnosis, not on psychosocial grounds or as a diagnosis of exclusion, but using positive diagnostic clinical signs, such as Hoover's sign of functional leg weakness or the entrainment test of functional tremor; 2) The central role of the neurologist in providing explanation, information, and triage of treatment (with some practical examples); 3) Increasing recognition of the evidence base for physiotherapy as well as psychological therapy; 4) Changes in the model that we use to think about the mechanism and aetiology of these problems which now incorporate biological as well as psychological factors.​

Wednesday, November 4, 2015
Plenary Lecture 8 - Victor & Clara Soriano Award Lecture​, 08:00-08:30, Hall A
The Physiology of Will, Mark Hallett, US
Free will is the perception that people have that they choose to make (most of) their movements.  This perception includes both a sense of willing the movement and self-agency that their act of willing was responsible for the movement that was made.  The physiology of free will is of interests to neurologists not only for its own sake but also because of the abnormalities of will often encountered in clinical practice.  For example, the movements in functional movement disorders look voluntary, but the patients experience them as involuntary.  Experiments show that even normal voluntary movements arise subconsciously and the perceptions of willing and agency arise after the fact.  There remains some controversy as to whether the sense of willing itself is a driving force for movement, but there do not need be any paradoxes if it is properly understood that the mind is a product of the brain.  ​

Thursday, November 5, 2015

Plenary Lecture 10 - Bharucha Award Lecture​, 08:00-08:30, Hall A
Guillain-Barré Syndrome and CIDP: One Disease or Many?, Richard Hughes, UK
This lecture honours the late Professor Eddie Bharucha, former President of the Indian Neurological Society, and Dr Piloo Bharucha, his wife and founder of the paediatric department at KEM Hospital. Guillain-Barré Syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) form a fascinating spectrum of diseases of varying severity, time course, anatomical distribution, pathology and system involvement. Painstakingly constructed, but arbitrary, diagnostic criteria have served the research community for epidemiological studies and recruitment into randomised trials. Astute clinical observations have added Fisher syndrome and multifocal motor neuropathy to the clinical spectrum. Within GBS, detailed pathological studies, characteristic antibodies and animal experiments have largely explained the pathogenesis of acute motor axonal neuropathy and distinguished it from acute inflammatory demyelinating polyradiculoneuropathy.  Other characteristic antibodies distinguish and explain Fisher syndrome.  Work continues to identify biomarkers and explain the pathogenesis of the rest of the GBS and CIDP spectrum. Paraprotein associated chronic inflammatory neuropathies with antibodies to minor myelin proteins or gangliosides inform this research.  Differences in treatment response of different members of the spectrum, most notably to corticosteroids, indicate different underlying mechanisms and complicate treatment of these, often very disabling, diseases.​

Plenary Lecture 11, 08:30-09:00, Hall A​
Can MRI Replace Clinical Neuro-Ophthalmology?, Christopher Kennard, UK

​Historically clinical neuro-ophthalmology was an area of neurology, par excellence, where the history and the clinical examination, which required a detailed knowledge of neuroanatomy, would usually provide the localization of the site of the pathological lesion and some indication of its underlying aetiology.  In many cases MRI can, often with even more accuracy, do as good a job of localization and pathological diagnosis.  But there is far more to being a clinical neuro-ophthalmologist than merely ordering an MRI scan. Firstly, clinical assessment needs to precede scanning to ensure that the appropriate scan is requested.  Secondly, there are many patients with neuro-ophthalmological disorders in whom the imaging is normal, who require a full history and detailed examination to enable the patient to be directed to other more timely and appropriate investigations. Thirdly, the neuro-ophthalmologist is essential to correctly interpret for the patient the relevance of non-specific or benign findings, which are often reported on MRI.  Finally, whatever the MRI scan may reveal a well trained neuro-ophthalmologist is then required to direct the patient to the most appropriate therapeutic procedure, be it a neurosurgical intervention, some pharmacological agent or masterly inactivity. Using a variety of neuro-ophthalmological patient histories the case will be made that despite the advent of MRI the clinical neuro-ophthalmologist is still essential for the provision of safe patient care and rapid diagnosis.​​

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