The Impact of Methylprednisolone Pulses during Relapses of Multiple Sclerosis on the Kinetics of Anti-Interferon-Beta Antibodies.

BACKGROUND/AIMS: We assessed the, hitherto unknown, impact of intravenous methylprednisolone (ivMP) pulses during relapses of multiple sclerosis (MS) on the kinetics of anti-interferon-beta neutralizing antibodies (Nabs) and binding antibodies (Babs). METHODS: Babs (ELISA) and Nabs (antiviral cytopathic effect assay) titers were evaluated before, immediately after and at 1 month following ivMP in 60 MS patients. RESULTS: ivMP reduces Nabs and Babs titers for at least 1 month. Baseline titers determine Nabs and Babs seronegativity at the end of ivMP. Clinical response to ivMP tends to be better in Nabs(+) patients. CONCLUSION: Sampling for Nabs/Babs should be avoided during or shortly after ivMP to avoid transient positive or negative results that may obscure the decision to switch treatment.

Effectiveness of a new modified intraluminal suture for temporary middle cerebral artery occlusion in rats of various weight.

Intraluminal temporary middle cerebral artery occlusion (MCAO) is a common model of ischemic stroke in the rat with significant, suture and weight-dependent variability along with increased risk of subarachnoid haemorrhage (SAH). Our purpose was to increase reproducibility and decrease SAH using a modification of the Koizumi suture. We compared a Koizumi 5/0 Ethilon poly-l-lysine-coated suture (s-2, group B) to an identical, uncoated one (s-1, group A) and the Belayev's 3/0 suture (s-3, group C), in the 2-h MCAO model in Wistar rats of varying weight (310-527 g). Assessment included successful infarction rates, the modified neurological stroke scale (mNSS), a modified Bederson's scale (mBS), the grid-walking test (GWT), infarction volume (with rostrocaudal subanalysis and analysis of cortical/striatal involvement) and hemispheric edema. The s-2 suture increased the successful MCAO from 61.1% and 66.6% (groups A and C) to 97.5% in group B and induced a more severe clinical stroke (P<0.05) irrespective of animal's weight, with no incidence of SAH. Infarction volume and ipsilateral hemispheric edema significantly (P<0.05) increased and well correlated with the mNSS (P

Evaluation of the stability of blood flow over time in the dominant hemisphere: a functional transcranial Doppler study.

Functional transcranial Doppler (fTCD) has been used for the identification of cerebral hemispheric dominance in various cognitive tasks. In our study, we have used fTCD with the aim to compare blood flow patterns in the hemispheres not only during the task activation periods but also in the post-stimulus phase. Normal volunteers, 25 right and 25 left-handed, were included. Mean flow velocities (FVs) in the bilateral middle cerebral arteries were recorded during the performance of six cognitive tasks and during the intervals between tasks. The lateralization index (LI) was calculated separately for each test (LI1-6), on the basis of the percent change of blood FV from baseline. To estimate flow fluctuations, a novel index, the LI-variability, was also calculated using a formula constituted by the minimum and maximum mean values recorded at specific time intervals during the entire procedure. Laterization indices, LI-3 and LI-4, corresponding to word generation and reading aloud tasks, produced the highest degree of activation. A perfect agreement (Cohen's kappa=1.000, P<0.001) was observed among LI-3, LI-4, and LI-V. The repetition of recordings gave excellent test-retest reliability in 10 randomly selected participants. Our results suggest that the hemisphere that is characterized as dominant by fTCD maintains a more stable flow pattern during the performance of successive cognitive tasks. Although it could not be considered as a clinically useful tool as yet, this observation introduces a novel parameter such as the stability of blood flow over time, which could potentially provide insight in the study of cerebral functions.

Neuroinflammation in multiple sclerosis: evidence for autoimmune dysregulation, not simple autoimmune reaction.

Both inflammatory and neurodegenerative components may contribute to the clinical profile of multiple sclerosis (MS) leading to irreversible deficits when they exceed the threshold of compensation. The mechanisms leading to tissue injury in MS are complex. Inflammation appears to be caused by overactive pro-inflammatory T-helper 1 cells, initiating an inflammatory cascade with several cellular and molecular immune components participating in the pathogenetic mechanism. Current treatments are most effective in the inflammatory phase of the disease since they may interfere with various stages of the immune cascade. Recent evidence has emerged that inflammation may not only be destructive, but may also play a part in tissue repair. This has opened up a new aspect of our knowledge of the role of the inflammatory process in MS. Data regarding the role of regulatory cells in particular, imply that specific immunomodulatory strategies that support the function of these particular cellular subpopulations may participate in the downregulation of autoimmune responses in MS.

Animal models of central nervous system immune-mediated diseases: therapeutic interventions with bioactive peptides and mimetics.

Experimental allergic encephalomyelitis (EAE) is a T helper 1 (Th1) mediated autoimmune disease and the principal animal model for multiple sclerosis (MS). Like MS, EAE is characterized by a coordinated inflammatory attack on the myelin sheath in the central nervous system (CNS), with damage to axons. No matter whether the ideal animal model is not yet available, much knowledge concerning the pathogenesis of MS has been achieved through studies on EAE. Dissecting the underlying immune mechanisms provided recognition of several myelin antigens that are vulnerable in autoimmune attack. The beneficial effect and the mechanism of action of a number of the currently used immunomodulating agents in MS therapy were first indicated in EAE. Altered peptide ligands (APL) can modulate T-cell responses to native peptide antigens implicated in the pathogenesis of autoimmune diseases such as MS and EAE. However, peptide therapy is hindered due to the sensitivity of peptides to proteolytic enzymes as well as due to some immune-mediated side effects. A number of cyclic myelin peptide analogs seem to be potential candidates in maintaining the biological function of the original peptide and effective in controlling inflammation in EAE. Additional data regarding the immunomodulating and neuroprotective effect of these much promising agents is required. Based on the data from studies on EAE models, clinical trials should also be designed in order to elucidate the impact of such APL-induced immune responses in MS disease activity. These clinical trials should carefully incorporate monitoring of both clinical, neuroimaging and immunological parameters.

[Findings from molecular imaging with SPET camera and 123I-ioflupane in the differential diagnosis of Parkinsonism and essential tremor].

The aim of the present study was to evaluate the use of the radiopharmaceutical 123I-ioflupane in the diagnosis and differential diagnosis of Parkinsonism (P) and essential tremor (ET). Forty-three consecutive patients, aged 35-72 years, presenting symptoms and signs compatible with P, plus 11 normal volunteers, aged 40-60 years, were enrolled for the study. The radiopharmaceutical was injected iv in a dose of 185 MBq and tomographic acquisition in a single-headed Pegasys gamma-camera (ADAC, USA), 3-4 hours post injection was performed in order to evaluate the activity of the presynaptic nigro-striatal dopaminergic transporter. After reconstruction and reorientation, semiquantitative analysis was performed evaluating counts/pixel: a) in the striatum and its parts (caudate nucleus and putamen) of both hemispheres and b) in the visual cortex representing non specific binding. According to our results, all 21 individuals with ET were correctly evaluated with this method, whilst 21/22 patients were diagnosed as having P. No statistical difference concerning the binding of the radioligand to the striatum and its parts was found between normal volunteers and patients with ET. Based on the present results in 21 of our patients, the diagnosis and treatment procedure were changed, while in the remaining 22 patients diagnosis and treatment were confirmed. According to our data, as well as to the data from others, molecular imaging (SPET) with 123I-ioflupane can properly differentiate individuals with ET from those having P, in order to avoid an unnecessary use of drugs that may even cause side effects. All our patients were re-examined after eight months. At that time the above results and the treatment that was given to them meanwhile, were positively evaluated.

Axonal damage in multiple sclerosis: a complex issue in a complex disease.

Multiple sclerosis is no longer considered to simply be an autoimmune demyelinating disease. Axonal destruction is another central pathological feature and a contributor to the accumulating disability of disease progression. The mechanism underlying axonal pathology has not been fully clarified but does not appear to be a simple one. The relationship between axonal damage and other components of the pathological features such as demyelination, inflammation and remyelination are under intense investigation. Experimental data suggest that therapeutic interventions such as the induction of rapid remyelination may lead to the protection of axons. In addition to immunomodulation, future strategies for neuroprotection may be of great importance.

20th meeting of the European neurological society, 19-23 june 2010, berlin, Germany.

More than 3000 neurologists attended the 20th Meeting of the European Neurological Society (ENS) and participated in the exciting and highly scientific programme. Eighty per cent of the submitted abstracts, which covered all aspects of neurology, were accepted. One major symposium, 16 oral presentations and 112 posters on multiple sclerosis (MS) were included in the programme. Additionally, there were three teaching courses and one interactive case presentation on MS.

19th meeting of the European Neurological Society 20 to 24 June 2009.

Around 3000 delegates took part in the 19th Meeting of the European Neuroligical Society (ENS) and all sessions were well attended. All aspects of Neurology were covered in the comprehensive programme which included one presidential symposium on stroke, three main symposia on epilepsy, muscle disorders and multiple sclerosis (MS), 140 oral presentations, 654 posters, 23 workshops and 23 teaching courses. Multiple Sclerosis was well represented with one symposium, 20 oral presentations, 103 posters, two teaching courses and two workshops. Overall 23 percent of the submitted abstracts were rejected.

Transplanted neural precursor cells reduce brain inflammation to attenuate chronic experimental autoimmune encephalomyelitis.

Stem cell transplantation was introduced as a mean of cell replacement therapy, but the mechanism by which it confers clinical improvement in experimental models of neurological diseases is not clear. Here, we transplanted neural precursor cells (NPCs) into the ventricles of mice at day 6 after induction of chronic experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Transplanted cells migrated into white matter tracts and attenuated the clinical course of disease. NPC transplantation down-regulated the inflammatory brain process at the acute phase of disease, as indicated by a reduction in the number of perivascular infiltrates and of brain CD3+ T cells, an increase in the number and proportion of regulatory T cells and a reduction in the expression of ICAM-1 and LFA-1 in the brain. Demyelination and acute axonal injury in this model are considered to result mainly from the acute inflammatory process and correlate well with the chronic neurological residua. In consequence to inhibition of brain inflammation, precursor cell transplantation attenuated the primary demyelinating process and reduced the acute axonal injury. As a result, the size of demyelinated areas and extent of chronic axonal pathology were reduced in the transplanted brains. We suggest that the beneficial effect of transplanted NPCs in chronic EAE is mediated, in part, by decreasing brain inflammation and reducing tissue injury.

Epidemiological data of multiple sclerosis in the province of Evros, Greece.

The frequency of multiple sclerosis (MS) in Greece is still debated. Our previous epidemiological field survey with a cross-check study of MS on March 31, 1984, in the province of Evros in north-eastern Greece showed a prevalence rate of 10.1/100,000. In 1990, Milonas et al. recorded a prevalence rate of 29.5/100,000 in northern Greece. So Greece is classified in the medium-frequency zone according to Kurtzke. This study was performed to estimate the prevalence of MS in the province of Evros and the annual incidence rates from 1974 to 1999. Patients were identified from several sources. A clinical follow-up was performed in 95% of the cases, and, if clinically indicated, new paraclinical examinations were performed and cases classified by Poser's criteria. The prevalence rate of the definite MS cases on December 31, 1999, was 38.9/100,000 and places the area in the high-risk zone. The mean annual incidence measured in 5-year intervals increased from 0.66/100,000 in 1974-1978 to 2.36/100,000 in 1994-1999 (p < 0.01). The increase in prevalence can be attributed to other causes than etiological changes, but the increase in the annual incidence rate indicates the possibility of a variation in risk factors of the disease.