MRI-based analysis of the natalizumab therapeutic window in multiple sclerosis.

The recommended natalizumab dosage is 300 mg every 4 weeks. We evaluated radiological activity at various times from the last natalizumab infusion by examining 386 magnetic resonance imaging (MRI) scans from 166 natalizumab-treated patients with relapsing-remitting MS. Of 113 scans performed >4 weeks after last natalizumab infusion, 26 were active (i.e. had ≥1 contrast-enhancing lesions). Risk of radiological activity increased by 1.34 fold for each week of delay with respect to the recommended 4-week dosing interval, compared with schedule-adherent patients (p<0.0001). Our data suggest that an increased MRI activity ≥7 weeks from the last infusion of natalizumab should be considered in cases of therapy discontinuation.

High prevalence and fast rising incidence of multiple sclerosis in Caltanissetta, Sicily, southern Italy.

BACKGROUND: Epidemiological studies conducted in Sicily and Sardinia, the two major Mediterranean islands, showed elevated incidence and prevalence of multiple sclerosis (MS)and a recent increase in disease frequency. OBJECTIVE: To confirm the central highlands of Sicily as areas of increasing MS prevalence and elevated incidence, we performed a follow-up study based on the town of Caltanissetta (Sicily), southern Italy. METHODS: We made a formal diagnostic reappraisal of all living patients found in the previous study performed in 1981. All possible information sources were used to search for patients affected by MS diagnosed according to the Poser criteria. We calculated prevalence ratios, for patients affected by MS who were living and resident in the study area on December 31, 2002. Crude and age- and sex-specific incidence ratios were computed for the period from January 1, 1993, to December 31, 2002. RESULTS: The prevalence of definite MS rose in 20 years from 69.2 (retrospective prevalence rate) to 165.8/100,000 population. We calculated the incidence of definite MS for the period 1970-2000. These rates calculated for 5-year periods increased from 2.3 to 9.2/100,000/year. CONCLUSION: This survey shows the highest prevalence and incidence figures of MS in the Mediterranean area and confirms central Sicily as a very-high-risk area for MS.

Modulatory effects of low- and high-frequency repetitive transcranial magnetic stimulation on visual cortex of healthy subjects undergoing light deprivation.

The aim of the present study was to explore further the effects of light deprivation (LD) on visual cortex excitability. Healthy subjects reporting reliable induction of phosphenes by occipital transcranial magnetic stimulation (TMS) underwent 60 min of complete LD. Phosphene threshold (PT) was measured before (T0), after 45 min (T1) and 60 min (T2) of LD, and then every 10 min after light re-exposure until recovery to T0 values. Repetitive TMS (rTMS) (at 1 or 10 Hz) was applied in separate sessions during the last 15 min of LD. PTs significantly decreased after 45 min of LD. rTMS differentially modified the effects of 60 min LD on PTs depending on stimulation frequency. One hertz rTMS did not change the decreasing of PT values as observed in baseline condition, but significantly prolonged the time to recover T0 PT values after light re-exposure. By contrast, 10 Hz rTMS significantly increased PT and the time to recover T0 PT values after light re-exposure was shortened. The results of this study show that the modulatory effects of different rTMS frequencies on visual cortex critically depend on the pre-existing excitability state of inhibitory and facilitatory circuits, and provide novel insights into the neurophysiological changes that take place in the visual cortex following functional visual deafferentation.

rTMS of the prefrontal cortex in the treatment of chronic migraine: a pilot study.

A recent fMRI study showed that dorsolateral prefrontal cortex (DLPFC) exerts an inhibitory control on pain pathways in humans. We investigated whether high-frequency rTMS over left DLPFC could ameliorate chronic migraine. Treatment consisted of 12 rTMS sessions, delivered in alternate days over left DLPFC. Sham rTMS was used as placebo. Eleven patients were randomly assigned to the rTMS (n=6) or to the placebo (n=5) treatment. Measures of attack frequency, headache index, number of abortive medications (outcome measures) were recorded in the month before, during and in the month after treatment. Subjects treated by rTMS showed a significant reduction of the outcome measures during and in the month after the treatment as compared to the month before treatment. No significant differences in the outcome measures were observed in the placebo group. High-frequency rTMS over left DLPFC was able to ameliorate chronic migraine. This is in agreement with the suggested role of DLPFC in pain control.

The serum level of free testosterone is reduced in amyotrophic lateral sclerosis.

Sporadic amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motoneurons. There is an approximately 2:1 higher incidence of ALS in men compared to women, and this has raised the hypothesis of an involvement of sex hormones in the etiopathogenesis of the disorder. In this work, the serum levels of dehydroepiandrosterone sulphate (DHEAS), 17-betaestradiol, free and total testosterone were measured in 35 patients with defined or probable ALS, according to the El-Escorial/WFN revisited criteria, and compared to those obtained from 57 disease controls, matched for age and gender to the ALS group. We found no differences between ALS cases and disease controls in the serum levels of DHEAS, 17-betaestradiol and total testosterone. Conversely, free testosterone was significantly decreased in the ALS group. Given that testosterone crosses the blood-brain barrier only as unbound form, we suggest a possible involvement of this sex hormone in the pathophysiology of this severe motor neuron disease.