Conference Report (42nd Annual Meeting of the Italian Society of Neurology, 22-25 October 2011, Turin, Italy)

Stephen D. Skaper

doi:10.2174/187152712799960718

Abstract

The Italian Society of Neurology (SIN), founded in 1907, held its 42nd national meeting in Turin, Italy during October 2011. The Society, currently numbering more than 3000 members, represents the largest gathering of clinical-oriented neurological sciences in Italy. This SIN meeting coincided with the 150th anniversary of the Unity of Italy, in a city that once served as the country's capital.

The meeting offered a number of workshops, courses, and translational science opportunities, together with plenary lectures given by internationally-recognized opinion leaders. In addition, the national meeting continues to place increasing emphasis on allowing young investigators and students to communicate their research findings. Although space does not permit, a few highlights are briefly discussed below.

Four symposia were dedicated to multiple sclerosis (MS). MS is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. It is estimated that there are about 2 million MS patients worldwide: it constitutes the most common non-traumatic neurological disorder among young adults. MS takes several forms, with new symptoms occurring either in discrete attacks (relapsing forms) or slowly accumulating over time (progressive forms). Although there is no known cure for MS, magnetic resonance imaging now allows for the quantification of tissue damage caused by macroscopic lesions as well as apparently normal tissue. Quantitative magnetic resonance imaging is capable of providing information also on the biochemical nature of structural alterations (e.g. demyelination and axonal damage), and as such is playing an increasingly important role in monitoring experimental therapies for MS. One such application had been in the recently completed clinical trial of Fingolimod, which showed a clear reduction in the risk of developing a second attack and with marked reduction in the number of new lesions.

Fingolimod is the lead molecule in a new class of drugs acting on the immune system by modulating the sphingosine-1-phosphate receptor (impeding lymphocyte migration into the central nervous system), and is the first oral treatment approved by the US Food and Drug Administration for MS. Considered as one of the top 10 innovations in medicine for 2011 (Cleveland Clinic). Recently completed clinical trials with Fingolimod indicate that this drug may be superior to interferon beta 1a in its ability to reduce inflammatory activity disability progression.

MS is frequently accompanied by motor disability, which affects the most socially and work-active population (young adults). Voltagedependent potassium channels, present on the axonal membrane and exposed (activated) following demyelinating damage of MS, are thought to be involved in such neuromotor problems. Blocking these channels (e.g. with the recently approved drugs such as Fampridine - chemical name 4-aminopyridine) improves visual function and motor skills and relieves fatigue in patients with MS, and is most effective with the chronic progressive form of MS. Fampridine has recently been approved both in the U.S. and Europe.

Three symposia were directed to Parkinson's disease (PD). PD is the most common chronic progressive neurodegenerative movement disorder, and is characterized by a profound and selective loss of nigrostriatal dopaminergic neurons. There are about 250 cases of PD for every 100,000 inhabitants. The current therapeutic ‘kit’ for PD includes, apart from the traditional L-DOPA, direct dopamine agonists and inhibitors of monoamine oxidase and catechol-O-methyl transferase. Unfortunately these drugs with time loose their efficacy, and are unable to control disease symptoms in the advanced stages. Moreover, the non-motor symptoms of PD do not respond to current therapies. Electrostimulation has proven of utility in a very limited number of patients to date. Unlike previous surgeries for PD, deep brain stimulation (DBS) does not damage healthy brain tissue by destroying nerve cells. Instead the procedure blocks electrical signals from targeted areas in the brain. Thus, if newer, more promising treatments develop in the future, the DBS procedure can be reversed. Although most patients still need to take medication after undergoing DBS, many experience considerable reduction of their PD symptoms and are able to greatly reduce their medications. The reduction in dose of medication leads to a significant improvement in side effects such as dyskinesias. In some cases, the stimulation itself can suppress dyskinesias without a reduction in medication. In the U.S., the National Institute of Neurological Disorders and Stroke is currently supporting research on DBS to determine its safety, reliability, and effectiveness, and to determine the site(s) in the brain where DBS surgery will be most effective in reducing PD symptoms.

New studies show that the utilization of sensory information and observing alterations in motor control and learning (e.g. by means of video clips) in patients with extrapyramidal disorders (PD, essential tremor, dystonia) can be used to improve walking capability.

Neuroinflammation is an area of vigorous research within the neuroscience community, at both the clinical and preclinical levels. Appropriately, a symposium dealing with the pharmacological modulation of microglia in neurodegenerative pathologies and neuroinflammation was held. Chronic neuropathic (or neurogenic) pain differs from other types of pain because it is not caused by physical injury. Unlike inflammatory or nociceptive pain, neuropathic pain represents a maladaptive response to a lesion or dysfunction that directly involves the somato-sensory system and manifests itself as hyperalgesia, allodynia and spontaneous pain. While neuropathic pain can arise as a consequence of a noxious event in the periphery, e.g. at the tissue or endoneural level, it can also occur as a result of noxae that are: primarily spinal, generally of a traumatic or degenerative nature; supraspinal (central) noxae of a traumatic, dysmetabolic or degenerative nature. A good example of this is the neuropathic pain not infrequently experienced by MS patients. Interactions between the nervous (neurons) and immune (non-neuronal cells) systems are now viewed as representing a key element in pain, including neuropathic, as well as in neurodegenerative diseases. Mast cells resident in innervated tissues and the endoneural compartment, and microglia at the spinal and supraspinal level â € “ together with their potential for crosstalk â € “ constitute highly promising targets for therapeutic intervention. In the case of microglia, the processes which modify their phenotype and determine a neuroinflammatory and/or neuroprotective direction remain to be fully understood. Pharmacological approaches have included antibiotics like minocycline to inhibit microglia proliferation, drugs aimed to specific targets such as chemokine receptors (e.g. fractakine) and, better still, agents capable of shifting cellular phenotype to an antiinflammtory and neuroprotective ‘form’. The classical cannabinoids and so-called endocannabinoids, while efficacious, are often handicapped by issues of tolerability/side effects. There is a growing appreciation that endogenous endocannabinoid-like molecules, the fatty acid amides of ethanolamine and, in particular palmitoylethanolamide (PEA), are capable of a modulatory inhibition of spinal and supraspinal microglia and peripherally located mast cells. Interestingly, microglia can synthesize and degrade PEA, suggesting an autocrine/paracrine mode of action. However, in a disease setting endogenous mechanisms may be inadequate, in which case exogenous administration of PEA may provide an innovative therapeutic approach oriented to the moderation of neuroinflammatory phenomena connected with these non-neuronal cells, in both chronic pain states and degeneration.

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