Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68%; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93%; the proportion of patients free from combined clinical activity was 65%; the proportion of patients free from MRI activity was 77%; and the proportion of patients free from any disease activity was 53%. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.

Triptans: over the migraine.

Migraine is a chronic, recurrent, disabling condition that affects millions of people worldwide. Proper acute care treatment for migraineurs is based on triptans, a class of specific medications approved over 20 years ago. Triptans are serotonin (5-HT1B/1D) receptor agonists that are generally effective, well tolerated and safe. Seven triptans are available worldwide, although not all are available in every country, with multiple routes of administration, giving to doctors and patients a wide choice. Despite the similarities of the available triptans, pharmacological heterogeneity offers slightly different efficacy profiles. Triptans are not pain medications, they are abortive migraine medications which cannot prevent migraines. In addition to migraine attacks, triptans are also helpful for cluster headaches. If they are useful in other primary headaches rather than migraine and cluster headache it is yet to be addressed. In the literature there are only limited controlled clinical data to support a migraine-selective activity for triptans. Reports are available about efficacy of triptans to stop attacks of other types of primary headache, such as tension type headache, hypnic headache and other rare forms of primary headaches. On the other hand, sumatriptan failed to treat the indomethacin-responsive primary headache disorders like chronic paroxysmal hemicrania and hemicrania continua, nor was it effective in the myofascial temporal muscle pain or in atypical facial pain. Why triptans are effective in so different types of primary headaches remain unclear. Up to date, it is not clear whether the antimigrainous activity of the triptans involves an action only in the periphery or in the CNS as well. Probably we should consider triptans as "pain killers" and not only as "migraine killers". We clearly need additional studies on triptans as putative analgesics in well-accepted animal and clinical models of acute and chronic somatic pain.

Migraine and movement disorders.

A large series of clinical and experimental observations on the interactions between migraine and the extrapyramidal system are available. Some previous studies reported high frequency of migraine in some basal ganglia (BG) disorders, such as essential tremor (ET), Tourette's syndrome (TS), Sydenham's chorea and more recently restless legs syndrome (RLS). For example, the frequency of migraine headache in a clinic sample of TS patients was found nearly fourfold more than that reported in the general population. To the best of our knowledge, no controlled studies have been conducted to determine a real association. ET and migraine headache have been considered comorbid diseases on the basis of uncontrolled studies for many years. In a recent Italian study, this comorbid association has been excluded, reporting no significant differences in the frequency of lifetime and current migraine between patients with ET and controls. Among mostly common movement disorders, RLS has been recently considered as possibly comorbid with migraine. Studies in selected patient groups strongly suggest that RLS is more common in migraine patients than in control populations, although no population-based study of the coincidence of migraine and RLS has yet been identified. The exact mechanisms and contributing factors for a positive association between migraine and RLS remain unclear. A number of possible explanations have been offered for the association of RLS and primary headache, but the three most attractive ones are a hypothetical dopaminergic dysfunction and dysfunctional brain iron metabolism, a possible genetic linkage and a sleep disturbance. More recently, the role of BG in pain processing has been confirmed by functional imaging data in the caudate, putamen and pallidum in migraine patients. A critical appraisal of all these clinical and experimental data suggests that the extrapyramidal system is somehow related to migraine. Although the primary involvement of extrapyramidal system in the pathophysiology of migraine cannot as yet be proven, a more general role in the processing of nociceptive information and/or maybe part of the complex behavioral adaptive response that characterizes migraine may be suggested.

Personality and endogenous/major depression: an empirical approach to typus melancholicus. 1. Theoretical issues.

The concept of typus melancholicus (TM) was shaped by Tellenbach by means of phenomenological analysis in order to describe the premorbid and intermorbid personality of endogenous depressives. In this paper, the authors delineate the core properties of TM-i.e. orderliness, conscientiousness, norm orientation and intolerance of ambiguity-as a point of departure for empirical-statistical research. Qualitative and quantitative studies inquiring the characteristics of TM are reviewed in order to point out its well-established personality dimensions. Alternating methodological steps are proposed, combining phenomenological hypotheses with empirical-statistical tests (hermeneutic complementarity) in order to validate and differentiate the TM concept. The question whether TM should be considered as a personality disorder and the ethical attitude of subsiding appreciation of the TM in different generations of psychiatrists are discussed. It is emphasized that the TM concept brings otherwise unsystematized observations of depressives' intermorbid personality features into a coherent theoretical framework.

The management of temperature during cardiopulmonary bypass: effect on neuropsychological outcome.

Laboratory studies demonstrate that mild degrees of brain cooling (2 degrees C to 5 degrees C) confer substantial protection from ischemic brain injury, and that mild elevation of brain temperature can be markedly deleterious. During hypothermic cardiopulmonary bypass (CPB) patients are made hypothermic and then rewarmed at a time when they are exposed to neurological insults. Our studies show that during rewarming, peak brain temperatures near 39 degrees C often are achieved inadvertently. We hypothesize that maintaining brain temperature < or = 34 degrees C during and after CPB will reduce the incidence of postoperative neuropsychological deficits. We present safety data from a study of 30 patients assigned either to conventional hypothermic CPB with rewarming or a protocol where brain temperature is raised only to 34 degrees C at the time of separation from CPB. There was no difference in bleeding, cardiac morbidity, or time to extubation between groups. We designed a neuropsychological test battery to detect postoperative neuropsychological deficits and tested its usefulness in a preliminary sample of 15 patients undergoing hypothermic CPB. We found patient acceptability and compliance were good. Sensitivity also seemed adequate in that 30% of patients were identified as having deteriorated at 1 week postoperatively compared to preoperatively, a result similar to that reported by others. Clinical trials of the efficacy of mild hypothermia in modulating brain injury in humans are needed before techniques of CPB can be designed to optimize neuroprotection.