Maria Letizia Bartolozzi

San Giuseppe Hospital, Ареццо, Tuscany, Italy

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Publications (36)164.57 Total impact

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    ABSTRACT: The accrual of brain focal pathology is considered a good substrate of disability in relapsing-remitting multiple sclerosis (RRMS). However, knowledge on long-term lesion evolution and its relationship with disability progression is poor. The objective of this paper is to evaluate in RRMS the long-term clinical relevance of brain lesion evolution. In 58 RRMS patients we acquired, using the same scanner and protocol, brain magnetic resonance imaging (MRI) at baseline and 10±0.5 years later. MRI data were correlated with disability changes as measured by the Expanded Disability Status Scale (EDSS). The annualized 10-year lesion volume (LV) growth was +0.25±0.5 cm(3) (+6.7±8.7%) for T2-weighted (T2-W) lesions and +0.20±0.31 cm(3) (+11.5±12.3%) for T1-weighted (T1-W) lesions. The univariate analysis showed moderate correlations between baseline MRI measures and EDSS at 10 years (p < 0.001). Also, 10-year EDSS worsening correlated with LV growth and the number of new/enlarging lesions measured over the same period (p < 0.005). In the stepwise multiple regression analysis, EDSS worsening over 10 years was best correlated with the combination of baseline T1-W lesion count and increasing T1-W LV (R = 0.61, p < 0.001). In RRMS patients, long-term brain lesion accrual is associated with worsening in clinical disability. This is particularly true for hypointense, destructive lesions.
    Multiple Sclerosis 07/2013; · 4.47 Impact Factor
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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; · 8.25 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; · 2.46 Impact Factor
  • A Panconesi, M L Bartolozzi, S Mugnai, L Guidi
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    ABSTRACT: Alcoholic drinks (AD) have been known as migraine triggers in about one-third of migraine patients in retrospective studies. We have reviewed the studies concerning the role of AD in triggering the various types of primary headaches published after the International Headache Society classification of 1988. There are many studies showing that AD are triggers of migraine without aura (MO), migraine with aura (MA), cluster headache (CH) and tension-type headache (TH). About one-third of MO and half of CH patients reported AD as trigger factors. Some studies show that AD are triggers in MA and TH in a similar percentage to that found in MO, but there are also discordant findings. There are sparse reports that AD are also triggers of less frequent types of primary headache such as familial hemiplegic migraine, hemicrania continua and paroxysmal hemicrania. The mechanism of alcohol-provoking headache is debated and should be compatible with the principal pathogenetic theories of primary headaches. If AD are capable of triggering practically all primary headaches, they should act at a common pathogenetic level. Vasodilatation is unlikely to be compatible as common mechanism. An action at cortical or more likely at subcortical level is plausible.
    Neurological Sciences 05/2012; 33 Suppl 1:S203-5. · 1.41 Impact Factor
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    ABSTRACT: To evaluate cognitive changes in a cohort of radiologically isolated syndromes (RIS) suggestive of multiple sclerosis (MS) and to assess their relationship with quantitative magnetic resonance (MR) measures such as white matter (WM), lesion loads, and cerebral atrophy. We assessed the cognitive performance in a group of 29 subjects with RIS recruited from 5 Italian MS centers and in a group of 26 patients with relapsing-remitting MS (RRMS). A subgroup of 19 subjects with RIS, 26 patients with RRMS, and 21 healthy control (HC) subjects also underwent quantitative MR assessments, which included WM T1 and T2 lesion volumes and global and cortical brain volumes. Cognitive impairment of the same profile as that of RRMS was found in 27.6% of our subjects with RIS. On MR scans, we found comparable levels of lesion loads and brain atrophy in subjects with RIS and well-established RRMS. In subjects with RIS, high T1 lesion volume (ρ = 0.526, p = 0.025) and low cortical volume (ρ = -0.481, p = 0.043) were associated with worse cognitive performance. These findings emphasize the importance of including accurate neuropsychological testing and quantitative MR metrics in subjects with RIS suggestive of MS. They can provide a better characterization of these asymptomatic subjects, potentially useful for diagnostic and therapeutic decisions.
    Neurology 01/2012; 78(5):309-14. · 8.25 Impact Factor
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    ABSTRACT: OBJECTIVES: To evaluate the incidence and dose-dependency of mitoxantrone (MTX)-associated acute myelocytic leukemia (AML) in the network of Italian multiple sclerosis (MS) clinics. METHODS: We performed a multicenter retrospective cohort study of patients treated with MTX in MS centers under the Italian national health care system between 1998 and 2008. Demographic, disease, treatment, and follow-up information were collected using hospital records. RESULTS: Data were available for 3,220 patients (63% women) from 40 Italian centers. Follow-up (mean ± SD) was 49 ± 29 months (range 12-140 months). We observed 30 cases of AML (incidence 0.93% [95% confidence interval 0.60%-1.26%]). The mean cumulative dose was higher in patients with AML (78 vs 65 mg/m(2), p = 0.028). The median interval from the start of therapy to AML diagnosis was longer than expected at 33 months (range 13-84 months); 8 patients (27%) developed AML 4 years or more after the first MTX infusion. The rate of mortality associated with AML was 37%. CONCLUSIONS: This higher than expected risk of AML and related mortality requires that treatment decisions must be made jointly between clinicians and patients who understand their prognosis, treatment options, and treatment-related risks. The now large exposed MS population must be monitored for hematologic abnormalities for at least 6 years from the end of therapy, to ensure the rapid actions needed for early diagnosis and treatment of AML
    Neurology 11/2011; 77(21-77):1887-95.. · 8.25 Impact Factor
  • PLoS ONE 04/2011; · 3.73 Impact Factor
  • Alessandro Panconesi, Maria Letizia Bartolozzi, Leonello Guidi
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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. · 1.67 Impact Factor
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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. · 3.73 Impact Factor
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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. · 4.47 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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    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. · 4.47 Impact Factor
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    Alessandro Panconesi, Maria Letizia Bartolozzi, Leonello Guidi
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    ABSTRACT: Short-lasting unilateral neuralgiform headache (SUNCT) and first division trigeminal neuralgia (TN) are rare and very similar periorbital unilateral pain syndromes. Few cases of SUNCT are associated with posterior skull lesions. We describe a 54-year-old man with symptoms compatible with both the previous painful syndromes, associated with a small posterior skull and a cerebellar hypoplasia. The short height and the reported bone fractures could be compatible with a mild form of osteogenesis imperfecta, previously described in one case associated with SUNCT. However, a hypoplastic posterior cranial fossa characterizes also Chiari I malformation. The difficult differential diagnosis between SUNCT and TN and their relation with posterior skull malformations is debated.
    The Journal of Headache and Pain 09/2009; 10(6):461-4. · 2.78 Impact Factor
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    Alessandro Panconesi, Maria Letizia Bartolozzi, Leonello Guidi
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    ABSTRACT: The original Wolff's vascular theory of migraine was supported by the discovery of a class of drugs, the triptans, developed as a selective cephalic vasoconstrictor agents. Even in the neurovascular hypothesis of Moskowitz, that is the neurogenic inflammation of meningeal vessels provoked by peptides released from trigeminal sensory neurons, the vasodilatation provoked by calcitonin gene-related peptide (CGRP) is considered today much more important than oedema. The role of cephalic vasodilatation as a cause of migraine pain was recently sustained by studies showing the therapeutic effect of CGRP receptor antagonists. We discuss the evidence against vasodilatation as migraine pain generator and some findings which we suggest in support of a central (brain) origin of pain.
    The Journal of Headache and Pain 07/2009; 10(5):317-25. · 2.78 Impact Factor
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    ABSTRACT: To assess whether neuropsychological tests and MRI measures could be used as predictors of short-term disease evolution in a population of patients with benign multiple sclerosis (B-MS). The definition of B-MS is controversial. Recent data suggest that neuropsychological tests and MRI measures can provide valuable information for a more correct definition and interpretation of B-MS. Sixty-three patients with B-MS (Expanded Disability Status Scale [EDSS] < or =3.0 and disease duration > or =15 years) underwent neuropsychological assessment using the Rao's Brief Repeatable Neuropsychological Battery and the Stroop Test. At that time, conventional brain MRI and magnetization transfer (MT) imaging was performed. White matter lesion load, global and regional brain volumes, and MT ratio in lesions and normal-appearing brain were measured. After a mean follow-up of 5 years, patients still having an EDSS score < or =3.5 were classified as still benign, whereas patients who had developed a secondary progressive course or who had an EDSS score > or =4.0 were defined as no longer benign (NLB). At end of follow-up, 29% of patients were classified as NLB. Male gender (hazard ratio [HR] = 2.9; 95% confidence interval [CI] 1.2-7.5; p = 0.02), number of neuropsychological tests failed (HR = 1.4; 95% CI 1.1-1.7; p = 0.003), and T1-weighted lesions (HR = 1.3; 95% CI 1.1-1.5; p = 0.002) were related to NLB status. In a model including these 3 variables, the NLB status was predicted with an accuracy of 82%. Cognitive assessment and MRI metrics can predict short-term disease evolution in benign multiple sclerosis (B-MS). This information can be useful to correctly identify patients with B-MS.
    Neurology 07/2009; 73(7):498-503. · 8.25 Impact Factor
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    ABSTRACT: To perform voxel-wise assessments of regional brain atrophy state and rate in subjects with relapsing-remitting (RR) multiple sclerosis (MS). Recently, attention has focused on defining the tissue compartments and regions within which brain atrophy occurs. These regional measures of brain volume changes may help to better define the nature of the pathology underlying MS. In this context, specific regional measures of grey matter (GM) volume changes can be obtained by using the voxel-based morphometry (VBM) approach. Fifty-nine subjects with RR MS underwent conventional MRI at baseline and after a mean follow-up period of 3 years. Cross-sectionally, two VBM analyses (SPM-VBM, based on the Statistical Parametric Mapping software package, and FSL-VBM, based on the FMRIB Software Library tools) were performed to assess cortical GM volumes in RR MS patients compared to 25 age- and sex-matched normal controls (NC). Longitudinally, FSL-VBM and the regional extension of the SIENA method (SIENAr) were both used to assess regional brain atrophy rate in the RR MS patients and its relationship with increases in T(2)-weighted white matter (WM) lesion volume over the follow-up period. Widespread decrease in cortical GM volume was found in the RR MS patients compared to NC. Both SPM-VBM and FSL-VBM showed similar involvement of cortical regions (frontal, temporal, parietal, occipital lobes and insula), with a close correlation between the numbers of significant voxels obtained with the two different procedures (r=0.73, p<0.001). After 3-year follow-up, both FSL-VBM and SIENAr showed a further significant reduction in GM volume in the lateral frontal and parietal cortices, bilaterally. Regional volume changes also appeared significantly pronounced in correspondence to the increase in T(2)-weighted WM lesion volume over the follow-up period. By using different methodologies, we showed similar widespread tissue loss in the cerebral cortex of patients with RR MS. This brain tissue loss further progresses over time, particularly in the fronto-parietal cortex and seems to be partially dependent upon the increase of lesion load.
    Journal of the neurological sciences 04/2009; 282(1-2):55-60. · 2.32 Impact Factor
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    ABSTRACT: The definition of benign multiple sclerosis (B-MS) is still controversial. This mainly takes into account the subject's motor ability, with little or no relevance to other important features such as cognition. Moreover, no paraclinical markers are currently available to reliably identify patients who will remain benign in the long term. To assess, by using quantitative magnetic resonance (MR) metrics, differences in tissue damage between B-MS patients after dividing them into two groups on the basis of their cognitive performance. Forty-seven B-MS patients (Expanded Disability Status Scale score </=3.0 and disease duration >/=15 years) underwent neuropsychological assessment through the Rao Brief Repeatable Battery and the Stroop Test. At that time, B-MS patients underwent conventional brain MR and magnetization transfer (MT) imaging. White matter lesion load, global and regional brain volumes, and MT ratio (MTr) in lesions and normal-appearing brain were measured. Quantitative MR measures were compared in cognitively impaired (CI-MS) and cognitively preserved (CP-MS) patients and in 24 demographically matched healthy controls. Test performance was correlated with MR changes in specific cortical regions. Eleven patients were classified as CI-MS, and 36 were classified as CP-MS. Both T2-weighted and T1-weighted lesion loads were higher (p = 0.05 and 0.001) in CI-MS than in CP-MS patients. Furthermore, CI-MS patients were characterized by more pronounced decrease in neocortical volume (p = 0.005) and cortical MTr (p = 0.02) values than CP-MS patients. Finally, test performance correlated significantly with MR changes in relevant cortical regions. Cognitive assessment and quantitative magnetic resonance can help to reliably identify benign multiple sclerosis patients.
    Neurology 09/2008; 71(9):632-8. · 8.25 Impact Factor
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    ABSTRACT: Several studies have reported lower focal demyelination and inflammatory activity in primary progressive multiple sclerosis (PPMS) than in relapsing-remitting MS (RRMS). However, very little is known about possible differences in damage and distribution that may occur within lesions visible on magnetic resonance imaging in the 2 forms of the disease. To evaluate differences in spatial distribution and structural damage of focal demyelinating lesions in patients with PPMS and RRMS. We acquired conventional magnetic resonance and magnetization transfer images in 24 PPMS and 36 RRMS patients (matched for sex, age, and disease duration) and 23 healthy sex- and age-matched controls. In each participant, we measured T2- and T1-weighted lesion volumes and magnetization transfer ratios in lesional and nonlesional brain tissues. The spatial distribution of focal demyelination was assessed using T2- and T1-weighted lesion probability maps in each patient group. Voxel-based procedures were performed. University hospital. Patients with PPMS had greater disability than those with RRMS, with 70% of PPMS patients and 11% of RRMS patients having relevant motor symptoms. The T1- and T2-weighted lesion volumes were higher in PPMS than in RRMS patients (P < .001). T1- and T2-weighted lesion probability maps showed that the maximum probability for lesions was higher in PPMS (peak probability, 45% and 29%, respectively) than in RRMS (peak probability, 33% and 19%, respectively) patients and was localized in the corona radiata. Voxelwise analysis of lesional magnetization transfer ratios gave overlapping results. Differences in cerebral pathologic involvement exist between RRMS and PPMS and contribute to variations in clinical disability.
    JAMA Neurology 02/2008; 65(2):236-43. · 7.58 Impact Factor
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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.
    JAMA Neurology 08/2007; 64(8):1157-61. · 7.58 Impact Factor
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    ABSTRACT: The trend to start disease-modifying therapy early in the course of multiple sclerosis makes it important to establish whether the benign form is a real entity. In previous studies, measures of magnetization transfer (MT) ratio (MTr) have been shown to provide good estimates of the amount of tissue damage occurring in multiple sclerosis brains. Thus, with the hypothesis that if benign multiple sclerosis patients were really benign, sensitive measures of subtle tissue damage would be less pronounced in these patients than in very early relapsing-remitting (RR) multiple sclerosis patients. We carried out conventional MRI and MT imaging in 50 patients with benign multiple sclerosis [defined as having Kurtzke Expanded Disability Status Score (EDSS) <3 and disease duration >15 years] and in 50 early RR patients selected to have similar disability (EDSS <3) and short disease duration (<3 years). Data were compared with those of 32 demographically-matched normal controls. We used a fully automated procedure to measure lesional-MTr, perilesional-MTr, normal-appearing white matter (NAWM) MTr and cortical-MTr. We found that, after correction for common effects of age, lesional-MTr and perilesional-MTr of benign patients were significantly (P < 0.0001) lower than WM of normal controls, but significantly (P < 0.0001) higher than corresponding tissues of RR patients. In NAWM and cortex, MTr values of benign patients were similar to those of normal controls (P > 0.5) and significantly higher than those of the RR patients (P < 0.0001 and P < 0.01, respectively). Similar differences in MTr measures between benign and RR patients were found when patient groups were selected to have no disability (EDSS < or = 2) and, for benign multiple sclerosis, very long disease duration (>20 years) or when both groups were matched for high lesion load (T2-weighted lesion volume >10 cm3). We conclude that lesional and non-lesional MTr values can be significantly less pronounced in benign multiple sclerosis than in a cohort of RR patients at their earliest disease stages, suggesting that brain tissue damage is milder in benign multiple sclerosis than in early RR disease. This can be due to an extraordinary beneficial response to demyelination of benign patients and may represent the evidence that benign multiple sclerosis truly exists and might be differentiated from other forms of this illness.
    Brain 09/2006; 129(Pt 8):2008-16. · 9.92 Impact Factor

Publication Stats

879 Citations
164.57 Total Impact Points


  • 2011–2013
    • San Giuseppe Hospital
      Ареццо, Tuscany, Italy
  • 2004–2013
    • Università degli Studi di Siena
      • Department of Medicine, Surgery and Neuroscience
      Siena, Tuscany, Italy
  • 2006–2012
    • University of Florence
      • Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino
      Florence, Tuscany, Italy