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Maria Laura Stromillo,
Antonio Giorgio,
Francesca Rossi,
Marco Battaglini,
Bahia Hakiki,
Gianmichele Malentacchi,
Mario Santangelo,
Claudio Gasperini, Maria Letizia Bartolozzi,
Emilio Portaccio,
Maria Pia Amato,
Nicola De Stefano
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ABSTRACT: BACKGROUND: The MRI incidental finding in asymptomatic subjects of brain white matter (WM) changes meeting the Barkhof criteria for the diagnosis of multiple sclerosis (MS) has been recently characterized as the radiologically isolated syndrome (RIS). This entity needs to be more specifically defined to allow risk stratification of these subjects. We used brain proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to assess metabolic changes in an RIS population. METHODS: Twenty-three RIS subjects who were classified according to the Okuda Criteria underwent (1)H-MRSI examination with a central brain (CB) volume of interest (VOI) to measure levels of N-acetylaspartate (NAA) and choline (Cho) normalized to creatine (Cr) in the whole CB-VOI, in lesional/perilesional and normal-appearing WM regions, and in the cortical gray matter (CGM). The (1)H-MRSI data were compared with those of 20 demographically matched healthy controls (HC). RESULTS: NAA/Cr levels were significantly lower in RIS than in HC in all regions (p < 0.005 for all). No differences in Cho/Cr levels were found in either brain region. A single-subject analysis showed that NAA/Cr levels were at least 2 SDs below the HC mean in the 44% of RIS in the normal-appearing WM and in the 61% of RIS in the CGM. CONCLUSION: Decreased brain NAA/Cr levels in a group of RIS subjects indicates that brain metabolic abnormalities suggestive of axonal damage can be significant even at this early disease stage. This information could be useful for stratifying RIS individuals with a high risk of progression to MS.
Neurology 05/2013; · 8.31 Impact Factor
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ABSTRACT: OBJECTIVE.: This project aims to investigate the role of alcoholic drinks (ADs) as triggers for primary headaches. METHODS.: Patients followed in the Headache Centre and presenting with migraine without aura, migraine with aura (MA), chronic migraine (CM), and tension-type headache (TH) were asked if their headache was precipitated by AD and also about their alcohol habits. Individual characteristics and drink habits were evaluated within two binary logistic models. RESULTS.: About one half (49.7%) of patients were abstainers, 17.6% were habitual consumers, and 32.5% were occasional consumers. Out of 448 patients, only 22 (4.9%), all with migraine, reported AD as a trigger factor. None of 44 patients with MA and none of 47 patients with TH reported AD as a trigger factor. Among those patients with migraine who consume AD, only 8% reported that AD can precipitate their headache. Multivariate analyses showed that AD use, both occasional and habitual, is unrelated to TH. Moreover, analysis performed among migraine patients, points out that occasional and habitual drinkers have a lower risk of presenting with CM than abstainers, although statistical significance occurred only among occasional drinkers. Only 3% of migraine patients who abstain from AD reported that they do not consume alcohol because it triggers their headache. CONCLUSION.: Our study shows that AD acts as headache triggers in a small percentage of migraine patients. Differing from some prior studies, our data suggest that AD do not trigger MA and TH attacks. Moreover, the percentage of abstainers in our sample is higher compared with that reported in general population surveys.
Pain Medicine 04/2013; · 2.35 Impact Factor
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ABSTRACT: Alcoholic drinks are a migraine trigger in about one third of patients with migraine in retrospective studies on trigger factors. Many population studies show that patients with migraine consume alcohol in a smaller percentage than the general population. Moreover, research has shown a decreased prevalence of headache with increasing number of alcohol units consumed. The classification criteria of alcohol-related headaches remain problematic. We discuss the role and mechanism of action of alcohol or other components of alcoholic drinks in relation to alcohol-induced headache. In accordance with data from a recent prospective study, we believe that reports overestimate the role of alcohol, as well as other foods, in the triggering of migraine. If a relationship between the intake of alcohol and the migraine attack is not clear, a small dose of alcohol is not contraindicated either for enjoyment or its protective effect on cardiovascular disease.
Current Pain and Headache Reports 02/2011; 15(3):177-84. · 1.66 Impact Factor
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Nicola De Stefano,
Maria Laura Stromillo,
Francesca Rossi,
Marco Battaglini,
Antonio Giorgio,
Emilio Portaccio,
Bahia Hakiki,
Gianmichele Malentacchi,
Claudio Gasperini,
Mario Santangelo, Maria Letizia Bartolozzi,
Maria Pia Sormani,
Antonio Federico,
Maria Pia Amato
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ABSTRACT: To improve the characterization of asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities highly suggestive of multiple sclerosis (MS), a condition named as "radiologically isolated syndrome" (RIS).
Quantitative MRI metrics such as brain volumes and magnetization transfer (MT) were assessed in 19 subjects previously classified as RIS, 20 demographically-matched relapsing-remitting MS (RRMS) patients and 20 healthy controls (HC). Specific measures were: white matter (WM) lesion volumes (LV), total and regional brain volumes, and MT ratio (MTr) in lesions, normal-appearing WM (NAWM) and cortex.
LV was similar in RIS and RRMS, without differences in distribution and frequency at lesion mapping. Brain volumes were similarly lower in RRMS and RIS than in HC (p<0.001). Lesional-MTr was lower in RRMS than in RIS (p = 0.048); NAWM-MTr and cortical-MTr were similar in RIS and HC and lower (p<0.01) in RRMS. These values were particularly lower in RRMS than in RIS in the sensorimotor and memory networks. A multivariate logistic regression analysis showed that 13/19 RIS had ≥70% probability of being classified as RRMS on the basis of their brain volume and lesional-MTr values.
Macroscopic brain damage was similar in RIS and RRMS. However, the subtle tissue damage detected by MTr was milder in RIS than in RRMS in clinically relevant brain regions, suggesting an explanation for the lack of clinical manifestations of subjects with RIS. This new approach could be useful for narrowing down the RIS individuals with a high risk of progression to MS.
PLoS ONE 01/2011; 6(4):e19452. · 4.09 Impact Factor
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Antonio Giorgio,
Emilio Portaccio,
Maria Laura Stromillo,
Silvia Marino,
Valentina Zipoli,
Marco Battaglini,
Anita Blandino, Maria Letizia Bartolozzi,
Gianfranco Siracusa,
Maria Pia Amato,
Nicola De Stefano
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ABSTRACT: Patients with multiple sclerosis (MS) who have a favourable clinical status several years after disease onset are classified as 'benign'. In many cases brain tissue damage does not differ between benign MS and the 'classical' MS forms.
To assess whether the favourable clinical course in benign MS could be explained by the presence of an efficient functional cortical reorganization.
Twenty-five right-handed patients with benign MS (defined as having Expanded Disability Status Scale ≤ 3 and disease duration >15 years) underwent functional MRI during a simple motor task (right-hand tapping) to assess movement-associated brain activation. This was compared with that of 10 patients with relapsing-remitting MS and 10 normal controls. Benign MS patients also underwent conventional brain MRI and magnetization transfer imaging, which was compared with an identical examination obtained 1 year before. Quantitative structural magnetic resonance measures were baseline and changes over time in T2-lesion volume, magnetization transfer ratio in T2 lesions and normal-appearing brain and total brain volume.
Movement-related activation was greater in patients with benign MS than in those with relapsing-remitting MS or normal controls, extensively involving bilateral regions of the sensorimotor network as well as basal ganglia, insula and cerebellum. Greater activation correlated with lower T2-lesion magnetization transfer ratio, and with decreasing brain volume and increasing T2 lesion volume.
The results suggest that bilateral brain networks, beyond those normally engaged in motor tasks, are recruited during a simple hand movement in patients with benign MS. This increased activation is probably the expression of an extensive, compensatory and tissue-damage related functional cortical reorganization. This can explain, at least in part, the favourable clinical expression of patients with benign MS.
Multiple Sclerosis 11/2010; 16(11):1326-34. · 4.26 Impact Factor
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ABSTRACT: We investigated the prevalence and the clinical association of high titer of antibodies against glutamic acid decarboxylase (hGADAb) among unselected patients with inflammatory/autoimmune disorders of the nervous system. By indirect immunofluorescence examination of samples from 1435 patients, we identified 7 cases (0.48%) with hGADAb. Although stiff-person plus syndrome was the commonest clinical accompaniment, most of the patients presented with a combination of different symptoms, including psychiatric disturbances and intestinal motility disorders. Diagnosis delay and chronic evolution were common findings. In two cases persistently high values of hGADAb over the years were observed. The rarity and the phenotype heterogeneity of hGADAb clinical association should not discourage clinicians from antibody screening, at least in selected cases, as an early immunotherapy can change the otherwise chronic progression of this complex disorder spectrum.
Journal of neuroimmunology 10/2010; 227(1-2):175-7. · 2.84 Impact Factor
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Emilio Portaccio,
Benedetta Goretti,
Valentina Zipoli,
Benedetta Nacmias,
Maria Laura Stromillo, Maria Letizia Bartolozzi,
Gianfranco Siracusa,
Leonello Guidi,
Antonio Federico,
Sandro Sorbi,
Nicola De Stefano,
Maria Pia Amato
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ABSTRACT: The objective of this article was to assess the association between apolipoprotein E (APOE)-epsilon4 and cognitive impairment (CI) in relapsing-remitting multiple sclerosis (RRMS). The APOE genotype was assessed in 85 RRMS cases (58 females, mean age 43 +/- 8.4 years, mean disease duration 15.8 +/- 9.6 years, mean Expanded Disability Status Scale (EDSS) 1.7 +/- 1.0). Cognitive functioning was evaluated in the whole sample using Rao's Brief Repeatable Battery (BRB). Performance on each test was assessed by applying the normative values for the Italian population. In a subgroup of 50 patients, a brain magnetic resonance (MR) study was performed including measurement of T2 lesion volumes (T2LV), neocortical volume (NCV) and normalized brain volume (NBV). The relationship between APOE genotype, CI and MR variables was assessed through univariate and multivariate logistic regression models. CI, most commonly involving complex attention and verbal memory tasks, was found in 28 cases (33%). We identified a total of 19 epsilon4carriers (22.4%), who did not differ from non-carriers regarding clinical and demographic characteristics. The presence of the epsilon4 genotype was associated with neither CI (p = 0.28) nor impairment on each neuropsychological test (p > 0.32; corrected for age, gender, disease duration, EDSS, depression and fatigue). The APOE genotype and CI were also not related in the subgroup of younger patients (age < 45 years; p > 0.9). Moreover, CI was related to higher T2LV (p = 0.008) and lower NCV (p = 0.006). In conclusion, in our sample CI was associated with higher subcortical damage and cortical atrophy but not with APOE-epsilon4 genotype. The role of APOE-epsilon4 as a possible biomarker in multiple sclerosis is still questionable.
Multiple Sclerosis 11/2009; 15(12):1489-94. · 4.26 Impact Factor
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Maria Pia Amato,
Emilio Portaccio,
Benedetta Goretti,
Valentina Zipoli,
Marco Battaglini, Maria Letizia Bartolozzi,
Maria Laura Stromillo,
Leonello Guidi,
Gianfranco Siracusa,
Sandro Sorbi,
Antonio Federico,
Nicola De Stefano
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ABSTRACT: We previously reported selective decreases of neocortical volumes in patients with early relapsing-remitting (RR) multiple sclerosis (MS) with mild cognitive impairment, with a good correlation between cortical volumes and cognitive measures.
To assess the relevance of gray matter changes over time to changes in cognition in RRMS.
A longitudinal survey after 2.5 years. Each patient underwent a magnetic resonance imaging (MRI) protocol identical to that performed at baseline; cognitive performance was reassessed with the Rao Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis.
Two university MS clinics.
Of 41 patients with RRMS who participated in the original cross-sectional study, 28 were available for the follow-up evaluation (18 women; mean +/- SD age, 37.1 +/- 8.9 years; mean +/- SD MS duration, 7.3 +/- 2.9 years; mean +/- SD Expanded Disability Status Scale score, 1.8 +/- 1.5).
We measured the percentage of brain volume changes, normalized cortical volume (NCV) changes, and normalized deep gray matter volume changes on conventional T1-weighted MRIs and changes in lesion load on T2-weighted MRIs. The number of tests failed on the Rao Brief Repeatable Battery were used to classify the patients as cognitively deteriorating or stable or improving.
We identified 12 of 28 cognitively deteriorating and 16 of 28 stable or improving patients. These subgroups did not differ in the mean +/- SD percentage of brain volume changes (-2.1% +/- 1.2% vs -1.3% +/- 1.3%; P = .11), normalized deep gray matter volume changes (-2.1 +/- 2.8 mL vs -0.6 +/- 3.1 mL; P = .60), and changes in lesion load on T2-weighted MRIs (1.9 +/- 2.6 mL vs 1.6 +/- 2.3 mL; P = .73). However, NCV changes were significantly higher in deteriorating than in stable or improving patients (-43.0 +/- 18.9 mL vs -17.8 +/- 26.6 mL; P = .007). In deteriorating patients, NCV changes were correlated with performance in a verbal fluency test (r = 0.73; P < .001). In a regression model, only NCV changes were significantly associated with deteriorating cognitive performance (odds ratio, 0.8; 95% confidence interval, 0.7-0.9).
Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.
Archives of Neurology 08/2007; 64(8):1157-61. · 7.58 Impact Factor
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ABSTRACT: The aim of the study was to assess neocortical changes and their relevance to cognitive impairment in early relapsing-remitting multiple sclerosis (RRMS). Conventional magnetic resonance was acquired in 41 RRMS patients and 16 demographically matched normal controls (NC). An automated analysis tool was used to obtain measures of cortical brain volumes normalized for head size. Neuropsychological performance of MS patients was assessed through the Rao's Brief Repeatable Battery. We identified 18 cognitively preserved (MS-cp) and 23 cognitively impaired (MS-ci) MS patients. Values of normalized cortical volumes (NCV) in the whole MS sample were lower than those in the NC group (p=0.01). MS-ci patients showed NCV values lower (p=0.02) than did both MS-cp patients and NC. Moreover, we found a positive correlation between NCV values and measures of verbal memory (r=0.51, p=0.02), verbal fluency (r=0.51, p=0.01) and attention/concentration (r=0.65, p<0.001) in MS-ci patients. Furthermore, NCV values were significantly decreased in patients who scored lower on a greater number of tests (r=-0.58, p<0.01) in the MS-ci group. Only MS-ci patients had cortical atrophy significantly correlated with a poorer neuropsychological performance. Grey matter pathology may contribute to the development of cognitive impairment in MS from the earliest stages of the disease.
Journal of the Neurological Sciences 06/2006; 245(1-2):195-9. · 2.35 Impact Factor
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Maria Pia Amato,
Jerome Grimaud,
Iuliana Achiti, Maria Letizia Bartolozzi,
Patrice Adeleine,
Hans-Peter Hartung,
Ludwig Kappos,
Alan Thompson,
Maria Trojano,
Sandra Vukusic,
Christian Confavreux
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ABSTRACT: The EDMUS system is a clinical database specifically tailored to the description of multiple sclerosis (MS). The EVALUED (Evaluation of the EDMUS system) study is an European project with two objectives: 1) to assess the inter-examiner reliability of the whole EDMUS system; 2) to validate the EDMUS-Grading Scale (EGS),which is a simplified version of the Kurtzke Disability Status Scale (DSS).
The protocol included 12 neurologists working in pairs within six European centres (Bari, Basel, Florence, London, Lyon, Würzburg). They assessed independently 30 MS patients in their centre, filling in the EDMUS forms. The reliability of the system was assessed on selected key items in the history of the MS onset, the clinical course and the disease course classification. The clinical examination of the patients permitted an assessment of the Kurtzke Expanded Disability Status Scale (EDSS) and the EGS. Level of agreement was measured in terms of kappa and weighted kappa indexes whenever appropriate.
The study included 180 patients with definite or probable MS of whom 37% were males. Age was 35.8+/-9.6 years (mean +/- SD), disease duration 7.8+/-5.7 years, and mean EDSS score 4.1+/-2.2. The disease course was relapsing-remitting in 67%, secondary progressive in 22%, and progressive from disease onset in 11%. For key items of the history, the inter-examiner reliability level ranged from moderate to excellent. Concerning the disability scales, perfect agreement was reached in 59 % for EDSS and 78% for EGS. The close correlation and linear association (r=0.94, p<0.0001) between both scales demonstrated EGS's construct validity.
The EDMUS system allows a consistent clinical description of MS using a common language. This standardized follow-up of MS patients is valuable especially in studies requiring a critical mass of informative patients.
Journal of Neurology 12/2004; 251(12):1472-80. · 3.47 Impact Factor
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ABSTRACT: Recent clinical and imaging studies have raised the hypothesis that patients with multiple sclerosis (MS) and the apolipoprotein E (ApoE) epsilon4 allele may have a more severe disease course than those without the ApoE epsilon4 allele. This seems to be related to more extensive tissue destruction and less efficient neuronal maintenance and repair in ApoE epsilon4 carriers.
To evaluate the influence of different ApoE genotypes on brain tissue integrity in patients with relapsing-remitting MS (RRMS).
We determined the ApoE genotype in 76 RRMS patients. Conventional T1-, T2-, and proton density-weighted magnetic resonance (MR) images were obtained for each patient and in a group of demographically matched healthy control subjects. On conventional T1-weighted MR images, an automated analysis tool was used to obtain total brain volumes normalized for head size (NBVs). Total brain lesion load was estimated on proton density- and T2-weighted MR images.
From the whole group of RRMS patients, we identified 18 with and 58 without the epsilon4 allele. Both patient groups were not significantly different in age, age of disease onset, clinical disability, and disease duration. Carriers of the epsilon4 allele showed significantly (P =.01) lower NBVs than controls and non-epsilon4 allele carriers. When a similar analysis was performed on only those patients with both very short disease duration and absence of clinical disability, NBV values were still significantly lower in RRMS patients with the epsilon4 allele than in those without it (P =.02) and in controls (P =.007). In contrast, RRMS patients with different ApoE genotypes did not show significant differences in values of total brain T2-weighted lesion volumes.
The presence of significant NBV decreases only in the group of RRMS patients with the ApoE epsilon4 genotype provides new evidence that links ApoE epsilon4-related impaired mechanisms of cell repair and severe tissue destruction in MS. Results of the present study suggest that this negative influence of the ApoE epsilon4 genotype might be active from the earliest disease stages.
Archives of Neurology 05/2004; 61(4):536-40. · 7.58 Impact Factor
