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Graziella Filippini

Publications and source records attributed to Graziella Filippini.

14 recordsLinked to original sources

Accuracy of magnetic resonance imaging for the diagnosis of multiple sclerosis: systematic review.

OBJECTIVE: To determine the accuracy of magnetic resonance imaging criteria for the early diagnosis of multiple sclerosis in patients with suspected disease. DESIGN: Systematic review. DATA SOURCES: 12 electronic databases, citation searches, and reference lists of included studies. Review methods Studies on accuracy of diagnosis that compared magnetic resonance imaging, or diagnostic criteria incorporating such imaging, to a reference standard for the diagnosis of multiple sclerosis. RESULTS: 29 studies (18 cohort studies, 11 other designs) were included. On average, studies of other designs (mainly diagnostic case-control studies) produced higher estimated diagnostic odds ratios than did cohort studies. Among 15 studies of higher methodological quality (cohort design, clinical follow-up as reference standard), those with longer follow-up produced higher estimates of specificity and lower estimates of sensitivity. Only two such studies followed patients for more than 10 years. Even in the presence of many lesions (> 10 or > 8), magnetic resonance imaging could not accurately rule multiple sclerosis in (likelihood ratio of a positive test result 3.0 and 2.0, respectively). Similarly, the absence of lesions was of limited utility in ruling out a diagnosis of multiple sclerosis (likelihood ratio of a negative test result 0.1 and 0.5). CONCLUSIONS: Many evaluations of the accuracy of magnetic resonance imaging for the early detection of multiple sclerosis have produced inflated estimates of test performance owing to methodological weaknesses. Use of magnetic resonance imaging to confirm multiple sclerosis on the basis of a single attack of neurological dysfunction may lead to over-diagnosis and over-treatment.

Case-Control Studies↗

Maternal medication use and the risk of brain tumors in the offspring: the SEARCH international case-control study.

N-nitroso compounds (NOC) have been associated with carcinogenesis in a wide range of species, including humans. There is strong experimental data showing that nitrosamides (R(1)NNO.COR(2)), a type of NOC, are potent neuro-carcinogens when administered transplacentally. Some medications are a concentrated source of amides or amines, which in the presence of nitrites under normal acidic conditions of the stomach can form NOC. Therefore, these compounds, when ingested by women during pregnancy, may be important risk factors for tumors of the central nervous system in the offspring. The aim of the present study was to test the association between maternal use of medications that contain nitrosatable amines or amides and risk of primary childhood brain tumors (CBT). A case-control study was conducted, which included 1,218 cases and 2,223 population controls, recruited from 9 centers across North America, Europe and Australia. Analysis was conducted for all participants combined, by tumor type (astroglial, primitive neuroectodermal tumors and other glioma), and by age at diagnosis (< or =5 years; >5 years). There were no significant associations between maternal intake of medication containing nitrosatable amines or amides and CBT, for all participants combined and after stratification by age at diagnosis and histological subtype. This is the largest case-control study of CBT and maternal medications to date. Our data provide little support for an association between maternal use of medications that may form NOC and subsequent development of CBT in the offspring.

Adolescent↗

Sporadic Creutzfeldt-Jakob disease: the extent of microglia activation is dependent on the biochemical type of PrPSc.

In prion-related encephalopathies, microglial activation occurs early and is dependent on accumulation of disease-specific forms of the prion protein (PrPSc) and may play a role in nerve cell death. Previously, we found that different types of PrPSc (i.e. type 1 and type 2) coexisted in approximately 25% of patients with sporadic Creutzfeldt-Jakob disease (CJD); and a close relationship was detected between PrPSc type, the pattern of PrP immunoreactivity, and extent of spongiform degeneration. To investigate whether microglial reaction is related to the biochemical type and deposition pattern of PrPSc, we carried out a neuropathologic and biochemical study on 26 patients with sporadic CJD, including all possible genotypes at codon 129 of the prion protein gene. By quantitative analysis, we demonstrated that strong microglial activation was associated with type 1 PrPSc and diffuse PrP immunoreactivity, whereas type 2 PrPSc and focal PrP deposits were accompanied by mild microglia reaction. These findings support the view that the phenotypic heterogeneity of sporadic CJD is largely determined by the physicochemical properties of distinct PrPSc conformers.

Adult↗

Household water source and the risk of childhood brain tumours: results of the SEARCH International Brain Tumor Study.

BACKGROUND: The period in utero is a time of increased vulnerability. Offspring of pregnant women exposed to carcinogenic substances in drinking water may be more likely to develop cancer. We examined whether household water source and the presence of nitrates or nitrites in residential water were associated with increased risks of childhood brain tumours (CBT). METHODS: We used data from a multicentre, case-control study with maternal information on residential water source, and nitrate/nitrite levels of tap water measured by dipstick. Subjects included 836 CBT cases and 1485 controls from five countries. RESULTS: The risks of CBT associated with reliance on well water (versus public water) during pregnancy varied widely, with significantly increased risks noted in two (of seven) regions and a decreased risk observed in one region. CBT risk did not increase with increasing nitrate levels. However, our results based on tap water tested in the pregnancy residences suggest the risk of astrocytoma may be associated with increasing levels of nitrite (odds ratio [OR] = 4.3, 95% CI: 1.4, 12.6 for nitrite levels of 1-<5 mg/l nitrite ion; OR = 5.7, 95% CI: 1.2, 27.2 of nitrite > or =5 mg/l). CONCLUSIONS: These results should be interpreted with caution because women's recollection of water sources may have contained inaccuracies, and nitrate and nitrite measurements, available for only a portion of subjects, were often obtained years after the pregnancies occurred. However, our results suggest a need for closer evaluation of well water content in some regions and the possibility that a nitrite-related water exposure may be associated with CBT.

Astrocytoma↗

Meningiomas invading the superior sagittal sinus: surgical experience in 108 cases.

OBJECTIVE: Radical resection of meningiomas invading the superior sagittal sinus (SSS) presents several hazards. Some surgeons consider SSS invasion a contraindication for complete resection, and others advocate total resection with venous reconstruction. There is a lack of published large series to provide definitive guidelines for the surgical treatment of these complex cases. We report our 15-year experience with surgery of parasagittal meningiomas invading the SSS. METHODS: Between 1986 and 2001, 108 patients (73 women, 35 men; age range, 22-83 yr; mean age, 56.2 yr) underwent surgery at the Neurological Institute "C. Besta" of Milan for tumors invading the SSS. Parasagittal meningiomas not invading the SSS were excluded from this series. RESULTS: Simpson Grade I to II removal was achieved in 100 patients. Thirty patients with meningiomas totally occluding the SSS had complete resection of the encased portion of the sinus. Histological examination revealed 86 benign (79.6%), 16 atypical (14.8%), and 4 malignant (3.7%) meningiomas along with 2 hemangiopericytomas. There were two perioperative deaths. Serious complications included brain swelling (nine patients; 8.3%) and postoperative hematoma (two patients; 1.85%). Follow-up ranged from 19 to 223 months (mean, 79.5 mo). One patient was lost to follow-up. Tumors recurred in 15 patients (13.9%). After multivariate analysis, histological type, tumor size, and Simpson grade were confirmed as significant independent prognostic factors for recurrence. CONCLUSION: On the basis of our results, we conclude that if the sinus is partially invaded, it can be opened to obtain as complete a resection as possible and to attempt to preserve the patency of the sinus. If the sinus is obstructed, the portion of the sinus involved can be resected completely. In both situations, extreme care is vital to preservation of cortical veins, which may offer important collateral drainage. With our approach, good results are achieved and it is not necessary to reconstruct the sinus.

Adult↗

Survival of 793 patients with amyotrophic lateral sclerosis diagnosed over a 28-year period.

We reviewed retrospectively 793 consecutive patients discharged with ALS diagnosis between 1971 and 1998 to identify survival predictors. Vital status in July 2001 was known for all patients. Mean age at onset was 56 (SD 11.7) years and mean age at diagnosis was 57.4 (SD 11.5) years. Onset symptoms were bulbar in 20.8% of patients. The median survival time from symptoms onset was 2.9 years (95% CI 2.7-3.1). Survival from onset was 93% after one, 48% after three and 24% after five years. Median survival was shorter in patients with time between onset and diagnosis <12 months than in those diagnosed> 23 months; (2.1 years vs. 5.9 years; P<0.001). Patients with onset after age 65 had a 4.2 times greater risk of death than patients less than 40 years. Bulbar onset was associated with 1.4 times greater risk of death than spinal onset. Patients diagnosed after 1990 had longer median survival (3.3 years) than those diagnosed in 1971-1979 (2.4 years) (P<0.001). As expected, age, bulbar onset and short time from onset to diagnosis were independent predictors of survival. We also found a significant increase in survival over time, probably due to improved comprehensive treatment of ALS patients in Italy.

Adult↗

Interferons in relapsing remitting multiple sclerosis: a systematic review.

BACKGROUND: Recombinant interferons have been approved by many national regulatory agencies for treatment of relapsing remitting multiple sclerosis, but widespread discussion continues about their true effectiveness, benefits, side-effects, and costs. METHODS: With the Cochrane Collaboration methodology, we reviewed all published, randomised, placebo-controlled trials of recombinant interferons undertaken in patients with relapsing remitting multiple sclerosis between 1993 and 2002. Our primary aim was to find out whether recombinant interferons reduced the number of patients who had clinical exacerbations and disease progression, compared with placebo. FINDINGS: The seven trials that met our criteria included 1215 randomised patients: data from 667 (55%) were available for analysis at 1 year's and from 919 (76%) at 2 years' follow-up. Interferon seemed to reduce the number of patients who had exacerbations during the first year of treatment (relative risk 0.73, 95% CI 0.54-0.99), but results at 2 years' follow-up were not robust and were difficult to interpret because of the many dropouts. Although the number of patients who had exacerbations (0.81, 0.74-0.89) or progressed (0.70, 0.55-0.88) during the first 2 years fell significantly in the protocol analysis, results were inconclusive after sensitivity analyses for exacerbations (1.11, 0.73-1.68) and disease progression (1.31, 0.60-2.89). Data were insufficient to establish whether steroid use and admissions to hospital were reduced in the interferon group. Similarly, MRI outcome data could not be analysed quantitatively. Side-effects were common, and acute toxic effects adversely affected quality of life. INTERPRETATION: Recombinant interferons slightly reduce the number of patients who have exacerbations during first year of treatment. Their clinical effect beyond 1 year is uncertain and new trials are needed to assess their long-term effectiveness and side-effects.

Adult↗

Relation of childhood brain tumors to exposure of parents and children to tobacco smoke: the SEARCH international case-control study. Surveillance of Environmental Aspects Related to Cancer in Humans.

The etiology of childhood brain tumors (CBTs) remains unknown. Tobacco smoke contains several known carcinogens and can induce DNA adducts in human placenta and hemoglobin adducts in fetuses. We present the results of an international case-control study to evaluate the association between CBTs and exposure of parents and children to cigarette smoke. The study was undertaken as part of the SEARCH program of the IARC. Nine centers in 7 countries were involved. The studies mainly covered the 1980s and early 1990s. Cases (1,218, ages 0-19 years) were children newly diagnosed with a primary brain tumor; there were 2,223 population-based controls. Most mothers who agreed to participate were interviewed in person at home. Odds ratios (ORs) were calculated by unconditional logistic regression, adjusted for age, sex and center, for all types of CBT combined, 4 CBT histotypes, 5 age groups and each center. There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life. These results did not change considering the child's age at diagnosis, the histologic type of tumor or center.

Adolescent↗

Accuracy of death certificates for amyotrophic lateral sclerosis varies significantly from north to south of Italy: implications for mortality studies.

OBJECTIVE: To evaluate the accuracy of death certificates (DCs) for amyotrophic lateral sclerosis (ALS) in different parts of Italy. Studies based on DC diagnosis for ALS have shown a reduced mortality comparing northern with southern Italy. These data are in contrast with results from other surveys on the incidence of ALS performed in Italy and other countries. METHODS: Archives of neurological clinics from northern (Milano, Monza, Pavia, and Bologna) and southern Italy including islands (Napoli, Sassari, Palermo, and Messina) were searched for patients discharged with a diagnosis of ALS in the period 1970-1995. Subjects affected by definite/probable ALS according to the Scottish Motor Neuron Disease Research Group diagnostic criteria were included. DCs were obtained from the vital statistic bureau. True positive rates (TPRs) and 95% confidence intervals (CIs) for proportions were calculated for northern and southern Italy separately. Multiple logistic regression analysis was performed according to gender, age at onset, age and year of death, and interval between onset and death. RESULTS: We found 651 patients affected by definite/probable ALS; 573 of them had died by December 31, 1996. DCs were available for 566 subjects (411 from northern Italy and 155 from southern Italy). TPR was 66.7% (95% CI 61.9-71.2) for northern Italy and 51.6% (95% CI 43.5-59.7) for southern Italy (chi(2) = 10.9, p = 0.001). Logistic regression analysis showed an association between a lower accuracy of DCs and the interval between onset of symptoms and death. TPR calculations considering different death periods (1970-1982 and 1983-1996) showed comparable rates of accuracy over time. CONCLUSIONS: Mortality statistics based on official death records do not accurately reflect interregional mortality for ALS in Italy.

Adult↗