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Biomedical subjects

L La Mantia

Publications and source records attributed to L La Mantia.

At least 19 recordsLinked to original sources

Tolosa-Hunt syndrome: critical literature review based on IHS 2004 criteria.

In 2004, the International Headache Society (IHS) re-defined the diagnostic criteria of Tolosa-Hunt syndrome (THS) specifying that granuloma, demonstrated by magnetic resonance imaging (MRI) or biopsy, is required for diagnosis. We reviewed the literature on THS published from 1988 (year of publication of first IHS criteria) to 2002, analysing individual cases in relation to the new IHS criteria. One hundred and twenty-four cases were identified. As far as it was possible to discern, clinical presentation was similar in all, but 44 (35%) were reported to have inflammation on MRI or bioptic evidence of granuloma, 41/124 (33%) had normal neuroimaging findings and 39 (31%) had a specific lesion, so the THS was secondary. These data confirm that clinical criteria for THS are common to several conditions and their application alone does not guarantee a correct diagnosis. The requirement for inflammation on MRI will result in better classification of painful ophthalmoplegias; nevertheless, an MRI protocol that best defines inflammation should be specified. The status of cases which fulfil the clinical criteria but have normal MRI remains to be clarified.

Clinical Trials as Topic↗

Interferon treatment may trigger primary headaches in multiple sclerosis patients.

Recent data have suggested that interferon-beta (IFN-beta) may aggravate headaches in multiple sclerosis (MS) patients. The aim of this study was to investigate the life-time prevalence of primary headaches in MS patients treated with interferons in comparison with patients treated with other disease-modifying agents. Attention was focused on the onset of headache and the changes in pre-existing headaches in relation to the onset of therapy. The study was open-labelled and not randomized. We studied 150 consecutive MS patients treated with IFN-beta (109 patients: 54 with 1b, 55 with 1a) and with other drugs (41 patients: 14 with glatiramer acetate, 27 with azathioprine). All patients underwent a semi-structured interview to diagnose headache type, according to the International Headache Society criteria. The frequency of primary headaches was higher in the interferon-group (72%) compared to patients in the other group (54%) (P=0.03). Worsening of pre-existing headaches or development of de novo headache occurred only in the interferon-group (41 and 48%, respectively) and not in the other group (P<0.001). These results show that headache should be considered among the side-effects of interferon in MS patients.

Adjuvants, Immunologic↗

Painful ophthalmoplegia: an unresolved clinical problem.

Painful ophthalmoplegia (PO) is an important presenting problem to ophthalmologists and neurologists. The etiological differential diagnosis is extensive, including different syndromes and causes (vascular, neoplastic, infectivous, inflammatory). Current neuroimaging techniques allow visualisation of the area of the suspected pathology. Some rare causes of PO, such as Tolosa Hunt syndrome with negative neuroimaging findings or ophthalmoplegic migraine remain till now of uncertain classification. Correct approach to the patient requires correlation to clinical data and careful monitoring, to avoid diagnostic mistakes, as the "history" of Tolosa-Hunt syndrome has underlined.

Diagnosis, Differential↗

A post-marketing study on immunomodulating treatments for relapsing-remitting multiple sclerosis in Lombardia: preliminary results.

The preliminary results of a post-marketing study on relapsing-remitting multiple sclerosis patients treated with immunomodulating agents attending the Lombardia Region's Multiple Sclerosis Centers are presented. A total of 294 patients treated with Betaferon (67), Avonex (115), Rebif 22 (45), Rebif 44 (18) and Copaxone (49) were included. Relapse frequency consistently decreases at 1 year and continues to decrease after 5 years of treatment, without differences between therapeutic groups. Eighty-seven out of 294 patients (29.6%) discontinued treatment for different reasons. Forty-eight of them shifted to a second therapeutic agent. A different trend, to lower or higher doses of interferon or immunosuppression, according to reasons of discontinuation, was observed.

Adjuvants, Immunologic↗

Headache and inflammatory disorders of the central nervous system.

The subcommittee of the International Headache Society for headache classification (ICHD-II) has recently recognised that secondary headaches may occur in patients affected by inflammatory diseases (ID) of the central nervous system (CNS), classifying them among the headaches attributed to non-vascular intracranial disorders. The aim of the study was to verify the association between headache and inflammatory non-infectious diseases of the CNS, by a review of the literature data on the topic, integrated by personal cases and data. Secondary headaches may occur in four main disorders: neurosarcoidosis (sec 7.3.1), aseptic (non-infectious) meningitis (7.3.2), other non-infectious ID (7.3.3) and lymphocytic hypophysitis (7.3.4). Headache and/or primary headaches are frequently reported in patients with neurosarcoidosis (30%), Behcet's syndrome (BS) (55%) and acute disseminated encephalomyelitis (45-58%). Recent data show a high incidence of headache also in multiple sclerosis (MS) (58%) (not mentioned in ICHD-II). The association between headache and inflammatory dysimmune diseases of the CNS, in particular BS and MS, might suggest a pathogenetic relationship.

Adult↗

Prevalence of primary headaches in people with multiple sclerosis.

The aim was to investigate the lifetime prevalence of headache and primary headache (diagnoses according to International Headache Society criteria) in multiple sclerosis (MS). The relationships between headache and clinical features of MS and MS therapy were also investigated. We studied 137 patients with clinically definite MS; 88 reported headache, 21 of whom developed headache after the initiation of interferon. The prevalence of all headaches in the remaining 116 patients was 57.7%. Migraine was found in 25.0%, tension-type headache in 31.9%, and cluster headache in one patient. A significant correlation (P = 0.007, Fisher's exact test) between migraine and relapsing-remitting MS was found. Primary headaches are common in MS patients. Further studies are needed to clarify the mechanisms underlying this association, particularly the association between migraine and relapsing-remitting MS, and the role of interferon in the development of new headache.

Adult↗

A post-marketing study on interferon beta 1b and 1a treatment in relapsing-remitting multiple sclerosis: different response in drop-outs and treated patients.

BACKGROUND: Interferon beta 1b (Betaferon) and 1a (Avonex) were licensed in Italy for treating relapsing-remitting multiple sclerosis in February 1996 and August 1997, respectively. OBJECTIVES: To evaluate the effectiveness of these agents on the basis of clinical experience in northern Italian multiple sclerosis centres. DESIGN: Clinical data on patients with relapsing-remitting multiple sclerosis were collected on an appropriate form from 65 centres in northern Italy. Intention to treat analysis was not possible, so patients who discontinued treatment (drop-outs) and who continued treatment (treated) were analysed separately. The main outcome measures were annual relapse frequency, number of relapse-free patients, mean change in extended disability status scale score (EDSS), and number of patients who worsened. RESULTS: 1481 patients were included; 834 were treated with Betaferon and 647 with Avonex for mean periods of 21.4 and 12.0 months, respectively. Basal EDSS was 2.37 and 2.17, respectively, and relapse frequency was 1.62 and 1.45. The annual relapse rate decreased by more than 60% with Betaferon and 55% with Avonex. The proportions of relapse-free, improved, and worsened patients were similar in the two groups. More patients interrupted treatment with Betaferon (41.1%) than with Avonex (15.3%); such patients showed more active disease at baseline and during treatment. The incidence of side effects was higher in Betaferon treated patients. CONCLUSIONS: The effectiveness of Betaferon and Avonex is confirmed. There was a more marked effect than expected from the experimental trial results. This might reflect differences in inclusion criteria, or, more likely, loss of drop-outs, favouring selective retention of responders.

Adjuvants, Immunologic↗

Cyclophosphamide for multiple sclerosis.

BACKGROUND: Multiple sclerosis is a presumed cell-mediated autoimmune disease of the central nervous system. Cyclophosphamide (CFX) is a cytotoxic and immunosuppressive agent, used in systemic autoimmune diseases. Controversial results have been reported on its efficacy in MS. We conducted a systematic review of all relevant trials, evaluating the CFX efficacy in patients with progressive MS. OBJECTIVES: The main objectives were to determine whether CFX slows the disease progression. SEARCH STRATEGY: Electronic databases (including MEDLINE, EMBASE, Cochrane Controlled Trials Register) were systematically searched. References list of retrieved studies and conference abstracts on the main meetings on Multiple Sclerosis were handsearched. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating the clinical effect of CFX treatment in patients affected by clinically definite progressive MS. CFX had to be administered alone or in combination with ACTH or steroids. The comparison group had to be placebo or no treatment or the same co intervention (ACTH or steroids) The main outcome criteria were : progression of disability (defined as an increase of 0.5 point in Kurtzke Extended Disability Status Scale (EDSS) for patients with baseline EDSS > or = 6 and 1 for EDSS < or = 5.5), differences of disability between treatment-control groups and the number of patients with side effects. DATA COLLECTION AND ANALYSIS: The identified references were reviewed by two reviewers who independently decided the eligibility of the study, extracted and summarized data and assessed the trial's quality. The statistical analysis was performed using the Cochrane RevMan software and analyzed using Cochrane MetaView. MAIN RESULTS: Of the 326 identified references, 80 were selected for full review, only four RCTs were selected for the final analysis. Intensive immunosuppression with CFX (alone or associated with ACTH or prednisone) in patients with progressive MS compared to placebo or no-treatment (152 participants) did not prevent the long -term (12-18-24 months) risk to evolution to a next step of EDSS. However, the mean change in disability (final disability subtracted from the baseline) significantly favoured the treated group at 12 (effect size - 0.21; C. I. - 0.24, - 0.17) and 18 months (- 0.19; C. I. - 0.24, - 0.14). We were not able to verify the efficacy of other schedules. Five patients died; sepsis and amenorrhea frequently occurred in treated patients (descriptive analysis). REVIEWER'S CONCLUSIONS: Only limited objectives were reached. This review shows a role of CFX in the treatment of progressive MS, but less toxic schedules must be considered, before its use in the clinical practice.

Cyclophosphamide↗

Transmigration of PBMNCs from beta-IFN-1b-treated MS patients: a one-year longitudinal study.

To evaluate the effects of in vivo beta-IFN-1b treatment on transmigration of mononuclear cells, we monitored for one year in vitro mononuclear cells trafficking through HUVECs monolayers stratified over a collagen gel during beta-IFN-1b treatment of 7 RR MS patients. The number of transmigrated cells was analysed before treatment (T0) and after 3 (T3), 6 (T6) and 12 months (T12); at the same time, levels of serum MMP-9 were quantified. The number of transmigrated cells decreased during treatment compared to pre-treatment values: the lowest number of transmigrated cells was detected at T3, and, although transmigration was still lower at T12, there was a trend to a return to pre-treatment levels over time. The amount of MMP-9 also decreased during therapy, although we could not find an absolute correlation between transmigration and levels of MMP-9, nor between either parameter and the clinical course of patients.

Adult↗

Magnetic resonance imaging, magnetisation transfer imaging, and diffusion weighted imaging correlates of optic nerve, brain, and cervical cord damage in Leber's hereditary optic neuropathy.

OBJECTIVES: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease leading to bilateral loss of central vision and severe optic nerve atrophy. A subtype of LHON presents additional clinical and MRI aspects indistinguishable from those of multiple sclerosis (MS) (LHON-MS). In patients with LHON or LHON-MS, an assessment was made of (a) the severity of optic nerve damage, using MRI and magnetisation transfer imaging (MTI), and (b) the presence and extent of macroscopic and microscopic pathology in the brain and cervical cord, using MRI and MT ratio (MTR) and mean diffusivity (D) histogram analysis. METHODS: Ten patients with LHON, four with LHON-MS, and 20 age and sex matched healthy controls were studied. For the optic nerve and the brain, dual-echo turbo spin echo (TSE), T1 weighted spin echo, and MT images were obtained. For the brain, fast fluid attenuated inversion recovery (fast FLAIR) and diffusion weighted images were also obtained. For the cervical cord, fast short tau inversion recovery (STIR) and MT images were obtained. The volume and the average MTR value of both the optic nerves were measured. MTR and histograms of the normal appearing brain tissue (NABT) and MTR histograms of the whole cervical cord tissue were created. RESULTS: The mean values of optic nerve volumes and MTR were significantly lower in patients with LHON than in healthy controls. Mean NABT-MTR histogram peak height was significantly lower in patients with LHON than in controls, whereas no significant difference was found for any of the cervical cord MTR histogram derived measures. Average diffusivity (D) was higher in patients with LHON than in controls. Optic nerve volume and MTR value and mean NABT-MTR were lower in patients with LHON-MS than in those with LHON. CONCLUSIONS: The severity of optic nerve pathology in LHON is measurable in vivo using MRI and MTI. MTR and histogram analysis suggests that microscopic brain damage occurs in LHON and that it is more severe in the MS-like form of the disease.

Adult↗

Long-term immunological changes in azathioprine-treated MS patients.

The long-term immunological effects of azathioprine treatment have been investigated in 8 multiple sclerosis patients with different course of disease, chronic progressive (CP) or relapsing progressive (RP). We studied fluctuations in peripheral blood mononuclear cell subsets, IgG, IgM and soluble vascular cell adhesion molecule-1 (sVCAM-1), before and after 2 (T24) and 3 (T36) years of therapy. We observed a significant decrease in CD8+ cells over time and a trend to lower percentage of CD3-CD56+ cells at T24 and T36. CD4+CD45RA+ cells in MS patients were lower than in healthy controls before therapy and reached values similar to those of healthy controls at T24 and T36. The remaining immunological parameters did not show any significant fluctuations.

Adult↗

Meta-analysis of clinical trials with copolymer 1 in multiple sclerosis.

Glatiramer acetate (copolymer 1) was licensed in the USA in 1996 for the treatment of relapsing-remitting multiple sclerosis. In order to assess its efficacy, a meta-analysis of all randomized controlled trials was performed. Two double-blind studies, accounting for a total number of 299 patients, contribute to this analysis. Patients undergoing the treatment have decreased probability of relapse at 12 months (OR 0.17, 95% CI 0.05-0.51, p = 0.002) and of unsustained progression of disability at 24 and 35 months (OR 0.57, 95% CI 0. 34-0.95, p = 0.031, and OR 0.50, 95% CI 0.28-0.90, p = 0.019). These data suggest that glatiramer acetate represents an alternative to interferon treatment in relapsing-remitting multiple sclerosis. However, further evidence of efficacy is required to justify its use in clinical practice.

Disease Progression↗

Role of microvascular decompression in trigeminal neuralgia and multiple sclerosis.

An excellent outcome after microvascular decompression for medically intractable trigeminal neuralgia in patients with multiple sclerosis is reported in seven of 15 cases. A dual cause could be hypothesised in some patients with multiple sclerosis and trigeminal neuralgia, and that microvascular decompression can be a therapeutic option.

Adult↗

Physical rehabilitation has a positive effect on disability in multiple sclerosis patients.

BACKGROUND: Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established. OBJECTIVE: We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial. METHODS: Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician. RESULTS: No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001). CONCLUSIONS: Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks.

Activities of Daily Living↗

Immunological effects of in vivo interferon-beta1b treatment in ten patients with multiple sclerosis: a 1-year follow-up.

Ten patients with multiple sclerosis and treated with interferon-beta1b (IFN-beta1b) were followed-up for 1 year with quantitation of serum VCAM-1 and ICAM-1 levels, mean fluorescence intensity of HLA-DR, VLA-4, CD11a, and CD18 on peripheral blood monocytes and lymphocytes, and adhesion of peripheral blood monocytes and CD45+ cells on endothelial cell monolayers. Adhesion molecule expression and adhesion of peripheral blood monocytes to endothelium were also monitored in healthy controls. No differences in adhesion were detected between MS patients before treatment and healthy controls, while after 1 year a marked decrease in the number of monocytes and mononuclear cells adhering to human umbilical vein endothelial cell monolayers was observed in patients treated with IFN-beta1b. After 1 year of treatment a significant increase in HLA-DR on peripheral blood monocytes was also detected. Our findings regarding lowered adhesion add information to available evidence of the mechanisms of action of IFN-beta1b in MS.

Adjuvants, Immunologic↗

Interferon beta treatment in relapsing-remitting multiple sclerosis: a post-marketing study in Lombardia, Italy. Multiple Sclerosis Centers of Lombardia, Italy.

The aim of the study was to evaluate the efficacy of interferon beta-1a (IFN-beta-1a) and beta-1b (IFN-beta-1b) in clinical practice for the treatment of relapsing-remitting multiple sclerosis (RR MS). Patients were selected and prospectively monitored according to a predefined protocol. An appropriate form was prepared to collect clinical data of multiple sclerosis patients attending the MS Centers of Lombardia, Italy. On 30 June 1998, 317 patients were treated with IFN-beta-1b and 156 with IFN-beta-1a. Basal expanded disability status scale (EDSS) and relapse frequency were similar in both groups of patients. The annual relapse rate consistently decreased from 1.76 to 0.63 at 1 year and to 0.51 at 2 years for the IFN-beta-1b group and from 1.6 to 1.0 at 1 year for the IFN-beta-1a group. Disability remained stable in most patients. Dropouts (20.5%) were affected by more active disease compared to patients who continued to be treated. This study confirms the efficacy of both treatments, showing a more marked effect than expected from the clinical trials' results, probably due to differences in selection criteria and exclusion of dropouts.

Adjuvants, Immunologic↗