Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register.

BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

Brain MRI white matter lesions in migraine patients: is there a relationship with antiphospholipid antibodies and coagulation parameters?

Brain magnetic resonance imaging (MRI) studies in migraine patients have demonstrated lesions consisting of focal regions of increased signal intensity within the white matter. Antiphospholipid antibodies are known to have a role in many diseases including migraine. The aim of the present study was to ascertain the relationship between MRI-visualized cerebral focal hyperintense lesions and serum antiphospholipid antibody levels, as well as blood coagulation parameters in migraine patients. One hundred and two (77 females, 25 males, mean age 33.8 +/- 11.1) consecutive migraine patients and a control group of 94 (70 females, 24 males, mean age 33.2 +/- 10.8) healthy subjects were enrolled. All individuals underwent brain MRI. Complete blood examinations, autoantibodies, antiphospholipids antibodies including anticardiolipin and lupus anticoagulant (aCL, LAC), antithrombin III, Protein C and S serum levels were ascertained in the subjects who presented white matter lesions on MRI. Twenty-seven (26.4%) migraine patients and six (6.3%) healthy subjects in the control group showed focal regions of increased intensity signal within cerebral white matter (odds ratio 5.3, 95% CI: 1.98-16.36). In migraine patients with white matter lesions, antiphospholipid antibodies were not detected and serum levels of antithrombin III, and proteins C and S were normal. White matter lesions in migraine patients are fairly common. This finding is not associated with antiphospholipid antibodies or abnormal coagulation parameters. The significance of such lesions at present remains unclear.

Occurrence of factor V Leiden mutation (Arg506Gln) and anticardiolipin antibodies in migraine patients.

The occurrences of factor V Leiden mutation (Arg506Gln) and antiphospholipid antibodies (APA) in migraine patients have been reported, but the findings are controversial. We investigated the presence of factor V Leiden and the serum level of anticardiolipin antibodies (aCL) in a consecutive series of 70 migraine patients (47 women; mean age, 34.1 years). Of these, 40 patients had migraine with aura. A matched sample of 70 healthy people was considered as the control group. Heterozygous genotype for factor V Leiden mutation was detected in 4 (5.7%) migraine patients (of which 2 had migraine with aura) and in 2 (2.8%) subjects of the control group. Although proportionally more migraine patients harbored the factor V Leiden mutation, this difference was not statistically significant, perhaps due to the small number of patients involved. We found normal serum levels of aCL in all migraine patients. Further studies and a long-term follow-up are warranted to determine the significance of this genetic abnormality in migraine.

Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency.

Two brothers with myopathic coenzyme Q10 (CoQ10) deficiency responded dramatically to CoQ10 supplementation. Muscle biopsies before therapy showed ragged-red fibers, lipid storage, and complex I + III and II + III deficiency. Approximately 30% of myofibers had multiple features of apoptosis. After 8 months of treatment, excessive lipid storage resolved, CoQ10 level normalized, mitochondrial enzymes increased, and proportion of fibers with TUNEL-positive nuclei decreased to 10%. The authors conclude that muscle CoQ10 deficiency can be corrected by supplementation of CoQ10, which appears to stimulate mitochondrial proliferation and to prevent apoptosis.

[Granulomatous idiopathic myositis at pediatric onset. Description of a case and a review of literature]. / Miosite granulomatosa idiopatica in età pediatrica. Descrizione di un caso e revisione della letteratura.

The authors report a case of granulomatous myositis in a child (the cases in literature begin between 13 and 72 years). Our case is peculiar because the histological report of granulomatous myositis was accompanied by an important rise in serum CPK level without any symptoms of muscular disease. The serum CPK level, for 18 months, fluctuated between 4.190 and 22.960 UI/L while no symptom occurred. The authors complete the article with a review of the literature about the granulomatous myositis.

[Sampling study on practitioners' attitude to the prevention of infectious endocarditis]. / Indagine campionaria sull'orientamento dei medici di base nella prevenzione dell'endocardite infettiva.

UNLABELLED: BACKGROUNDS AND METHODS: The opinions and the experience of Veneto practitioners about prevention of infective endocarditis were detected through a sample survey among the 386 practitioners of Health and Social Unit Nr 16, 17, and 36 of Veneto Region. The interview was carried out through a questionnaire, sent by mail, asking for: 1) general information on the practitioner's profession; 2) information about the previous experience in diagnosis and care of heart diseases, particularly of infective endocarditis, of atrial septal defect ostium secundum type without pulmonary hypertension, of unstable angina, and moderate mitral stenosis; 4) attitudes in the prevention of infective endocarditis. Of 386 practitioners surveyed, 186 (48.2%) responded. More than 60% of the responders held a diploma of specialization and 7% were cardiologists, half of the responders had worked in public hospitals. The 63.8% of the practitioners had patients over sixty in a percentage of 15-44%. In 1990 only 5.9% of the practitioners observed new cases of infective endocarditis, while half of them stated that some of their patients had suffered from this disease in the past. RESULTS: The assessment of the level of severity for every heart disease is ranged between 0 (the minimum) and 10 (the maximum). The statistical analysis showed that the minimum arithmetic mean (+/- SD) is given for atrial septal defect without pulmonary hypertension with 4.6 +/- 2. Then for moderate mitral stenosis with 7.1 +/- 1.6, unstable angina pectoris with 7.4 +/- 2 and the maximum mean is given for infectious endocarditis with 8 +/- 1.7. ANOVA statistical analysis applied on the four paired series of assessment of severity carried out a high significant difference (F of Snedecor = 328.2; P < 0.001) among assessments, and among practitioners (F = 1.71; P < 0.01). High significant linear correlation (at least P < 0.01) is observed among the severity of the four heart diseases. Vice versa not significant association is showed between severity for every heart diseases and the experience of the interviewed. CONCLUSIONS: Most practitioners would prescribed prophylaxis for infective endocarditis to patients with rheumatic valve disease (91% of the responders), with previous episodes of infective endocarditis (90.4%), with prosthetic valve (67.6%) or with degenerative valve disease (57.3%). On the contrary most practitioners would not prescribe the prevention for infective endocarditis to patients with coronary heart disease (84.9%), with coronary bypass (71.4%), with mitral valve prolapse without insufficiency (60.6%), with dilatative cardiomyopathy (67%) or with obstructive cardiomyopathy (57.8%). A prevailing trend in case of congenital heart disease and mitral valve prolapse with insufficiency was not observed. The 86.6% of practitioners would prescribe the prophylaxis for infective endocarditis in case of dental extraction, but only the 64.4% would prescribe it in case of any potentially haemorrhagic oral or dental procedure. The 61.7% of the responders would not prescribe the prevention for infective endocarditis to patients receiving the prophylaxis for rheumatic fever. The practitioners would use in the following order: amoxicillin (77.3%), erythromycin (76.9%), penicillin V (76.3%) and ampicillin-gentamycin (61.3%). On the contrary, most responders would prescribe neither tetracycline (73%) nor spiramycin (69.8%). There is no prevailing trend to the employ of oral cephalosporins. The 90.3% of the practitioners think that infective endocarditis can be a quite interesting and useful subject for an up-to-date course.

Aging is associated with a diffuse impairment of forebrain cholinergic neurons.

The study evaluates whether any degenerative changes affect forebrain cholinergic systems during natural aging. The medial septal nucleus, the nuclei of the diagonal band, the neostriatum, and the basal nucleus were studied in adult and aged Wistar rats. Butcher's technique for acetylcholinesterase allowed us to identify neurons located in these forebrain nuclei, which stained intensely or moderately for the enzyme and were putatively cholinergic. The size of forebrain regions containing stained neurons, and the number and size of stained perikarya located therein, were measured. In aged rats, the size of forebrain cholinergic nuclei was reduced by an average of 26%. The density of neurons located in these regions was also significantly lower in aged rats than in controls; intensely stained neurons displayed a mean reduction of 27.81%, while intensely and moderately stained perikarya together were reduced by 25.43%. Cross-sectional area of the stained perikarya was also reduced in aged rats by 32.87%. These data show that the number of forebrain acetylcholinesterase-containing neurons is reduced in aged rats. They are consistent with the hypothesis that natural aging brings about a diffuse and homogeneous depletion of forebrain cholinergic perikarya. Neurons which are viable, and can be selectively stained, show morphological alterations, which are likely to be related to a degenerative process.

Age-dependent loss of cholinergic neurones in basal ganglia of rats.

A morphometric study of the striatal complex has been performed in adult and aged rats, by means of Butcher's acetylcholinesterase (AChE) staining. The size of neostriatum, and the number of putatively cholinergic AChE-positive perikarya, are significantly reduced in two-year-old rats. Consequently, mean cell density is decreased in the striatal complex by 15.58%; age-dependent loss is more pronounced: (1) in the dorsal and lateral parts of neostriatum, which in adults have a higher neural density; and (2) in the ventromedial part, which in the aged becomes almost void of neurones. It is concluded that depletion of cholinergic perikarya is a specific feature of natural ageing, which affects diffusely the neostriatum, and particularly its ventromedial territories.

[Idiopathic orthostatic hypotension (Shy-Drager syndrome). Clinical and hemodynamic studies of a case]. / Ipotensione ortostatica idiopatica (sindrome di Shy-Drager). Osservazioni cliniche ed emodinamiche in un caso.

A case of idiopathic orthostatic hypotension (Shy-Drager syndrome) in a 50-year-old man is reported. The diagnosis was made after other possible causes of orthostatic hypotension had been excluded. The Authors emphasize the need for a correct diagnosis in order to adopt an adequate symptomatic therapy, and to avoid useless and often harmful treatments.