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Biomedical subjects

G L Mancardi

Publications and source records attributed to G L Mancardi.

At least 19 recordsLinked to original sources

Prevalence of oedema of the lower limbs in multiple sclerosis patients: a vascular and lymphoscintigraphic study.

The aim of the study was to evaluate the frequency of oedema of the lower limbs in multiple sclerosis (MS) patients utilizing a multidisciplinary approach. A total of 205 patients with definite MS were included in the study. Seventy-five were male and 130 female, with a mean age of 50.53, mean Expanded Disability Status Scale (EDSS) score of 5.27 and mean disease duration of 16.6 years. Seventy-one patients had a relapsing-remitting (RR) disease course, 85 were secondary progressive (SP) and 49 were primary progressive (PP). Ninety-three patients (45%) showed oedema at the examination. EDSS, disease duration and disease course, but not gender, were statistically different between oedema and non-oedema patients. Out of 93 patients with oedema, 69 agreed to undergo a vascular examination. Of 69 patients, 45 (65.2%) had a CEAP score (specific rating scale for oedema) of 3 (presence of oedema) and 24 (34.8%) had a score of 4 (presence of a trophic disorder). Out of 69 subjects, 33 agreed to undergo a lymphoscintigraphy, which was normal in only 29 extremities out of 66. Lower limb oedema is common in MS patients, especially in those with reduced mobility. Early screening is advised in patients with an elevated EDSS.

Adult↗

The prevalence of multiple sclerosis in the north-west Italian province of Genoa.

UNLABELLED: The objective of this study was to assess the prevalence of multiple sclerosis (MS), calculated as point prevalence on 31 December 1997, in the province of Genoa, North-western Italy. METHODS: The province of Genoa is located in North-western Italy, an area of 1,835 km(2). On the point prevalence day the population consisted of 913,218 inhabitants. MS cases were identified by analysing archives of the hospitals with neurological or rehabilitation wards, neurologists serving the community, files of local chapters of the Italian MS society, all requests for oligoclonal bands analysis on CSF in the studied area. Patients included in the study were MS cases diagnosed before 31 December 1997 according to the Poser criteria resident in the province under study. RESULTS: A total of 857 subjects were alive and residing in the province of Genoa on the prevalence day. The overall crude prevalence rate was 94 per 100,000 (95% CI 88-100); 291 were males (34%) with a crude prevalence of 67 per 100,000 (95 % CI 60-76) and 566 were females (66%) with a prevalence of 118 per 100,000 (95% CI 108-128). The female/male ratio was 1.9. When age and sex were adjusted to the Italian standard population of 1991 prevalence was 85 per 100,000. Five hundred and thirty two out of the 857 patients agreed to be interviewed. The interviewed sample was representative of the prevalence sample: sex and gender distributions were identical in the two samples. The overall mean age was 48 (+/-13) years (48 +/-12 years in males; 48+/-14 years in females). Mean disease duration was 15 (+/-10) years for males and 16 (+/-11) years for females. Two hundred and ninety one (55 %) subjects had a relapsing remitting (RR) clinical course, 150 (28%) were secondary progressive (SP) and 91 (17%) were primary progressive (PP). Mean EDSS score was 5 (+/- 2; median 5). The mean age at time of onset was 33 (+/-10) years for males and 32 (+/- 11) years for females. The disease onset was monosymptomatic in 76% (n=407) patients and polysymptomatic in 24% (n=125). The mean length of time between clinical onset and diagnosis was 5 (+/- 6) years. CONCLUSION: We confirmed that the province of Genoa is a very high risk area for MS. We found a high rate of patients with a PP course; also the proportion of patients with high disability scores is greater compared to previous studies.

Adult↗

Antiepileptic medications in multiple sclerosis: adverse effects in a three-year follow-up study.

Neuropathic pain and paroxysmal symptoms are common in multiple sclerosis (MS) patients, although no double-blind clinical trial has been conducted to support antiepileptic medications (AED) use in MS. The aim of the study was to evaluate the frequency of AED utilisation and reported adverse events, in a cohort of MS patients. For a period of 3 years the rationale for prescribing AED, adverse effects, treatment duration and reasons for discontinuation were recorded in a database. Carbamazepine (CBZ) was prescribed in 36 patients, with adverse effects reported in 20 cases, of which 12 mimicked a relapse. Gabapentin (GBP) was prescribed in 94 patients, with adverse effects reported in 16 cases and in one case mimicked a relapse. Lamotrigine (LMT) was prescribed in 22 patients, with adverse effects reported in 4 cases, none mimicking a relapse. The present study found a significantly higher incidence of adverse effects in patients treated with CBZ, with a high rate of discontinuation at low dosages and episodes of evident worsening of neurological functioning compared to GBP or LMT.

Adult↗

Neurological research in Italy in 2003 and 2004.

We quantified Italian researchers' share of the scientific papers published in peer-reviewed medical Journals in the field of neurology in 2003 and 2004. The findings show that Italian researchers' gained an overall 7% share of peer-reviewed articles. This percentage places Italy in fourth place immediately after the United States, Great Britain and Germany.

Animals↗

Intense immunosuppression followed by autologous stem cell transplantation in severe multiple sclerosis.

Aggressive forms of multiple sclerosis (MS) represent a limited group of demyelinating diseases that rapidly progress to severe disability. Currently available therapies are poorly effective against these clinical entities. Recently, it has been demonstrated that intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT) can affect the clinical course of individuals with severe MS and completely abrogate the inflammatory activity detected by MRI. We report the result of the Italian phase 2 GITMO study, a multicentre study in which 21 MS patients, who were rapidly deteriorating and not responding to the usual therapeutic strategies, were treated with this procedure. The clinical effect of the treatment is long lasting, with a striking abrogation of inflammation detected by MRI findings. These results support a role for intense immunosuppression followed by ASCT as treatment in rapidly evolving MS cases unresponsive to conventional therapies.

Adult↗

The prevalence of pain in multiple sclerosis: a multicenter cross-sectional study.

In a multicenter cross-sectional study, the authors assessed pain in patients with multiple sclerosis (MS) using a symptom-oriented approach. Out of 2,077 questionnaires, we used 1,672 for data analysis. Pain and frequencies included trigeminal neuralgia 2%, Lhermitte's sign 9%, dysesthetic pain 18.1%, back pain 16.4%, and painful tonic spasms 11%. Comparison between different groups showed significant differences for age, Expanded Disability Status Scale, disease duration, and disease course, but not for sex. This study underlines the relevance of pain in the clinical history of MS.

Adolescent↗

Italian version of the Chicago multiscale depression inventory: translation, adaptation and testing in people with multiple sclerosis.

Depression is the commonest psychiatric disturbance in people with multiple sclerosis (MS), with prevalence higher than in the general population and other chronic diseases. However, accurate assessment of depressive symptoms can be biased by somatic symptoms which are part of both MS and depression. We translated and adapted into Italian the Chicago multiscale depression inventory (CMDI) and assessed its acceptability, internal consistency and test-retest reliability in 213 MS outpatients and 213 individually matched healthy controls. The questionnaire was also tested in 32 people with major depression. Acceptability, internal consistency, and test-retest reliability were good overall. We found greater odds for depressive symptoms in people with MS than healthy controls, with highest odds ratio for somatic symptoms (vegetative subscale). The Italian CMDI is characterized by good acceptability, internal consistency, and test-retest reliability. These findings support the use of the CMDI in Italian subjects with MS to screen for and follow depressive symptoms.

Adolescent↗

Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease: facts and uncertainties underlying the causal link between animal and human diseases.

Following an outbreak of bovine spongiform encephalopathy (BSE) in dairy cows in the United Kingdom (UK), 153 definite and probable human cases of new variant Creutzfeldt-Jakob disease (nvCJD) have been reported, almost exclusively in the UK. Although exposure to the BSE agent is the most plausible interpretation for the occurrence of nvCJD, the causal link between the BSE prion and nvCJD is still debated. This review discusses the pros and cons of nvCJD as a separate nosographic entity, the scientific basis for a correlation between BSE and nvCJD, the validity of the current diagnostic criteria for CJD and nvCJD, the contribution of epidemiology to the detection of a causal relation between BSE and nvCJD, and the present and future directions of the epidemiological research on BSE, CJD and nvCJD.

Animals↗

Marburg type and Balò's concentric sclerosis: rare and acute variants of multiple sclerosis.

Marburg type and Balò's concentric sclerosis are considered particular variants of multiple sclerosis, clinically characterized by a severe, rapidly evolving clinical course, and by unusual neuropathological changes, often large tumor-like demyelinating plaques in Marburg type and concentric layers of partial demyelination alternating with demyelinating bands in Balò's concentric sclerosis. These forms now can be diagnosed in vivo, with complete clinical and laboratory examination and MRI follow up. Although in some patients a favourable clinical course has been described, the poor prognosis of the majority of these cases justifies a treatment with intense immunosuppression.

Brain↗

The 14-3-3 protein in multiple sclerosis: a marker of disease severity.

CONTEXT: In multiple sclerosis (MS) axonal damage is an early event and is probably to be considered the most relevant cause of permanent and progressive disability. OBJECTIVES: To investigate the value of the increase of 14-3-3 and tau proteins in the cerebrospinal fluid (CSF) as peripheral markers of axonal pathology and predictors of disease evolution. PATIENTS AND METHODS: In the CSF samples obtained from 63 patients with demyelinating diseases (DD), including 20 clinically isolated syndromes (CIS) and 43 clinically defined MS, as well as from 56 controls, we analysed the presence of 14-3-3 reactivity by immunoblot analysis along with the concentration of tau protein by sandwich ELISA. RESULTS: The percentage of DD subjects showing a positive 14-3-3 protein CSF reactivity (38%) was significantly higher than the one previously detected, and was correlated in the MS patients with a more severe clinical phenotype in terms of degree of disability and rate of disease progression, during a 10-month mean clinical follow-up. On the contrary, the levels of the CSF-tau protein were highly variable in DD and control subjects, and the mean CSF-tau concentration was similar in both groups. CONCLUSIONS: The immunoblot analysis of 14-3-3 protein in the CSF could be a useful marker to identify a subgroup of DD patients with high risk of developing severe disability.

14-3-3 Proteins↗

Brain tissue loss occurs after suppression of enhancement in patients with multiple sclerosis treated with autologous haematopoietic stem cell transplantation.

To assess whether brain tissue loss occurs after profound and sustained suppression of magnetic resonance imaging (MRI) enhancement, we measured brain volume changes from 10 patients with rapidly evolving secondary progressive multiple sclerosis (MS) treated with autologous haematopoietic stem cell transplantation and followed up for 24 months. An average yearly decrease of brain volume of about 1.9% was observed despite only five enhancing lesions seen on triple dose follow up scans of two patients. This indicates that, in MS, progressive loss of tissue can occur independently of concomitant MRI-visible inflammation.

Artifacts↗

Symptomatic medication use in multiple sclerosis.

Multiple sclerosis (MS) is one of the most studied neurological diseases, although scarce attention has been placed on symptomatic therapy. The aim of the study was to evaluate the frequency of medication prescription for the major symptoms related to MS in order to better understand the needs of patients. The study was conducted during an epidemiological survey in the province of Genoa, Italy. Out of 856 patients with MS in the study area, 665 agreed to participate in a structured interview. Two hundred and forty-nine (37%) subjects, with a mean age of 53 years and a mean Expanded Disability Status Scale (EDSS) score of 5.2, were taking at least one symptomatic medication. Four hundred and sixteen (63%) subjects, with a mean age of 49 years and a mean EDSS score of 4.5, were not using symptomatic therapy. The most commonly treated symptoms were pain (28%), spasticity (27%) and mood disorder (16%), while bladder dysfunction (8%) and fatigue (3%) were less frequently treated with medication. Seventy-seven patients (12%) were taking medications for reasons not directly related to MS. This cross-sectional study underlines the frequency of medication prescription for symptoms such as spasticity and pain, while other common symptoms, such as bladder dysfunction and fatigue, may perhaps be undertreated. The present findings also underline the need for clinical trials on symptomatic therapies.

Adult↗

EAE in the common marmoset Callithrix jacchus.

The common marmoset Callithrix jacchus is a primate phylogenetically close to humans which, when immunized with myelin proteins, is susceptible to a form of experimental autoimmune encephalomyelitis (EAE) that resembles multiple sclerosis (MS). Neuropathological features of marmoset EAE, including inflammation, demyelination and axonal injury, are strikingly similar to findings in the human disease and are the final result of a joint autoimmune attack by myelin-specific T and B cells. The molecular and functional similarity of the marmoset immune system, together with the availability of diagnostic tools that can be used in humans (such as magnetic resonance imaging), makes the marmoset EAE a unique model with which to evaluate the safety and efficacy of therapeutic strategies for the treatment of MS.

Animals↗

Pain and MS.

Pain is frequently evident in the course of multiple sclerosis (MS) and is estimated to occur in approximately 50% of patients. The incidence of pain has no apparent correlation to disease severity. Moreover, a comprehensive definition of pain has not been established, thus making the evaluation of this chronic, evolving symptom difficult. On the basis of its pathophysiology, pain can occur as a consequence of neurological impairment and disability, somatic pain or because of neurological damage. Although there are few randomized trials for pain in MS, new therapeutic strategies are now available and interest in the symptomatic treatment of MS is growing.

Humans↗

Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS.

BACKGROUND: Autologous hematopoietic stem cell transplantation (ASCT) has been recently utilized with encouraging results in patients with poorly controlled MS. OBJECTIVE: To determine in severe cases of MS the effect of ASCT on gadolinium (Gd)-enhanced MRI and to obtain information on clinical course and safety. METHODS: In a cooperative study, 10 patients with rapidly evolving secondary progressive MS were transplanted, after BEAM conditioning regimen (carmustine, etoposide, cytosine-arabinoside, and melphalan), with unmanipulated autologous peripheral blood SC mobilized with high-dose cyclophosphamide (CY; 4 g/m2) and granulocyte-colony-stimulating factor. Triple-dose Gd-enhanced scans were performed monthly for a pretreatment period of 3 months and compared with serial monthly Gd-enhanced MRI for the following 6 months and then once every 3 months. RESULTS: The median follow-up is now 15 months (range 4 to 30 months). The number of Gd-enhancing lesions decreased immediately after mobilization with CY and finally dropped to zero in all cases after the conditioning regimen. The number of new T2-weighted positive lesions paralleled data obtained for Gd-enhanced MRI. Clinically, patients improved slightly or remained stable. CONCLUSION: These results demonstrate that the therapeutic sequence CY-BEAM-ASCT has the capacity to completely suppress MR-enhancing activity, an effect that is sustained with time. The final impact of this procedure on disease course remains to be established.

Adult↗

Insulin treatment enhances expression of IGF-I in sural nerves of diabetic patients.

We studied the expression of insulin-like growth factor I (IGF-I) and its receptor in sural nerves from 8 diabetic patients divided into insulin-treated (IT) and non-insulin-treated (NIT) groups, compared with 5 patients with axonal neuropathies and 4 control patients (undergoing biopsies for diagnostic purposes). Insulin-like growth factor I mRNA levels did not differ in diabetic cases compared with control subjects. In sural nerves from IT patients and axonal neuropathies, IGF-I expression was higher than in NIT subjects and diagnostic controls. Changes in IGF-I receptor mRNA levels paralleled those of the ligand. Insulin-like growth factor I immunoreactivity was higher in nerves undergoing axonal degeneration and higher in IT than NIT diabetic patients and diagnostic controls. These findings suggest that insulin treatment increases IGF-I expression in diabetic nerves. Our data do not support the hypothesis of an absolute IGF-I deficiency in human diabetic neuropathy. A Schwann cell's incapacity to increase IGF-I expression after severe nerve damage, as happens in axonal neuropathies, may be a cofactor in the pathogenesis of diabetic neuropathy.

Adult↗

The D355V mutation decreases EGR2 binding to an element within the Cx32 promoter.

Mutations in the early growth response 2 (EGR2) gene are associated with some forms of Charcot--Marie--Tooth disease (CMT) and other demyelinating neuropathies. These mutations modify the EGR2 binding to specific DNA sequences suggesting a role in the transcriptional control of myelination-specific genes. Here we show that the D355V mutation, associated with a CMT case combining axonal and demyelinating abnormalities, reduces three times the affinity of EGR2 to its consensus sequence and ten times its affinity to a sequence in the human Cx32 promoter. These findings could indicate that this EGR2 mutation leads to the development of CMT1 through the transcriptional deregulation of Cx32 gene.

Adolescent↗