G. Tedeschi

Brain atrophy and lesion load in a large population of patients with multiple sclerosis

Objective: To measure white matter (WM) and gray matter (GM) atrophy and lesion load in a large population of patients with multiple sclerosis (MS) using a fully automated, operator-independent, multiparametric segmentation method. Methods: The study population consisted of 597 patients with MS and 104 control subjects. The MRI parameters were abnormal WM fraction (AWM-f), global WM-f (gWM-f), and GM fraction (GM-f). Results: Significant differences between patients with MS and control subjects included higher AWM-f and reduced gWM-f and GM-f. MRI data showed significant differences between patients with relapsing-remitting and secondary progressive forms of MS. Significant correlations between MRI parameters and between MRI and clinical data were found. Conclusions: Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability.

GABA(B) receptor 1 polymorphism (G1465A) is associated with temporal lobe epilepsy

Background: Dysfunction of γ-aminobutyric acid (GABA) (B) receptors has been implicated in the pathogenesis of temporal lobe epilepsy (TLE). Objective: To evaluate the genetic contribution of cloned human GABA(B) receptors to TLE. Methods: The authors genotyped 141 patients (78 women and 63 men; mean age = 49.1 ± 18.0 years) with nonlesional TLE and 372 age- and sex-matched normal individuals for the known polymorphism G1465A in the human GABA(B) receptor 1 [GABA(B[1])] gene. Results: There was a highly significant overrepresentation of the G1465A heterozygote in patients with TLE compared with controls. The A/G genotype was found in 17% of the 141 patients with TLE and in only 0.5% of the 372 controls (p < 0.0001). The authors also found that patients carrying the A allele had a significantly higher risk (p = 0.003, OR = 6.47, 95% CI = 2.02 to 20.76) of developing drug-resistant TLE. Furthermore, the age at onset of seizures tended to be lower in patients with A/G genotype, but the difference was not significant. Conclusions: The results of this study indicate that the GABA(B[1]) polymorphism (G1465A) confers a highly increased susceptibility to TLE. Moreover, it seems to influence the severity of this common epileptic disorder.

Subcortical motor plasticity in patients with sporadic ALS : An fMRI study

OBJECTIVE To address the potential contribution of subcortical brain regions in the functional reorganization of the motor system in patients with sporadic ALS (sALS) and to investigate whether functional changes in brain activity are different in sALS patients with predominant upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction. METHODS We studied 16 patients with sALS and 13 healthy controls, using BOLD-fMRI, while they performed a simple visually paced motor task. Seven patients had definite clinical UMN signs while nine patients had prevalent clinical and electrophysiological LMN involvement. fMRI data were analyzed with Brain Voyager QX. RESULTS Task-related functional changes were identified in motor cortical regions in both patients and healthy controls. Direct group comparisons revealed relatively decreased BOLD fMRI responses in left sensorimotor cortex, lateral premotor area, supplementary motor area and right posterior parietal cortex (p < 0.05 corrected) and relatively increased responses in the left anterior putamen (p < 0.001 uncorrected) in sALS patients. Additional analyses between the two patients subgroups demonstrated significant BOLD fMRI response differences in the anterior cingulate cortex and right caudate nucleus (p < 0.001 uncorrected) with more robust activation of these areas in patients with greater UMN burden. Importantly, there were no significant differences in performance of the motor task between sALS patients and controls as well as between sALS patient subgroups. CONCLUSIONS Our data demonstrate a different BOLD fMRI pattern between our sALS patients and healthy controls even during simple motor behavior. Furthermore, patients with sALS and greater UMN involvement show a different reorganization of the motor system compared to sALS patients with greater LMN dysfunction.

Role of perfusion-weighted imaging at 3 Tesla in the assessment of malignancy of cerebral gliomas

PurposeThis study was performed to clarify the role of perfusion-weighted imaging (PWI) at 3 Tesla in the characterisation of haemodynamic heterogeneity within gliomas and surrounding tissues and in the differentiation of high-grade from low-grade gliomas.Materials and methodsWe examined 36 patients with histologically verified gliomas (25 with high-grade and 11 with low-grade gliomas). PWI was performed by first-pass gadopentetate dimeglumine T2*-weighted echo-planar images, and cerebral blood volume (CBV) maps were computed with a nondiffusible tracer model. Relative CBV (rCBV) was calculated by dividing CBV in pathological areas by that in contralateral white matter.ResultsIn high-grade gliomas, rCBV were markedly increased in mass [mean±standard deviation (SD), 4.3±1.2] and margins (4.0±1.1) and reduced in necrotic areas (0.3±0.3). Oedematous-appearing areas were divided in two groups according to signal intensity on T2-weighted images: tumour with lower (nearly isointense to grey matter) and oedema with higher (scarcely isointense to cerebrospinal fluid) signal intensity. Tumour showed significantly higher rCBV than did oedema (1.8±0.5 vs. 0.5±0.2; p<0.001) areas. In low-grade gliomas, mass (2.0±1.5) and margin (2.2±1.2) rCBV were significantly lower than in high-grade gliomas (p<0.001).ConclusionsThree-Tesla PWI helps to distinguish necrosis from tumour mass, infiltrating tumour from oedema and high-grade from low-grade gliomas. It enhances the magnetic resonance (MR) assessment of cerebral gliomas and provides useful information for planning surgical and radiation treatment.RiassuntoObiettivoChiarire il ruolo dell’imaging pesato in perfusione (PWI) a 3 Tesla nella caratterizzazione dell’eterogeneità emodinamica dei gliomi cerebrali e dei tessuti circostanti, e nella differenziazione dei gliomi di alto grado da quelli di basso grado.Materiali e metodiAbbiamo esaminato 36 pazienti con gliomi verificati istologicamente (25 con alto ed 11 con basso grado). Il PWI è stato ottenuto mediante immagini eco-planari T2*-pesate con primo passaggio di gadopentetato di dimeglumina, e le mappe di volume ematico cerebrale (CBV) sono state elaborate con il modello del tracciante non diffusibile. Il volume ematico cerebrale relativo (rCBV) è stato calcolato dividendo il CBV nelle aree patologiche per quello nella sostanza bianca controlaterale.RisultatiNei gliomi di alto grado, l’rCBV appariva marcatamente incrementato nella massa (media±SD, 4,3±1,2) ed ai margini (4,0±1,1), e ridotto nelle aree necrotiche (0,3±0,3). Le regioni apparentemente edematose sono state divise in due gruppi sulla base dell’intensità di segnale nelle immagini pesate in T2: “tumore” con più basso segnale (quasi isointenso alla sostanza grigia) ed “edema” con segnale più elevato (quasi isointenso al liquido cefalorachidiano). Le aree “tumore” presentavano rCBV significativamente più elevato rispetto a quelle “edema” (1,8±0,5 vs 0,5±0,2; p<0,001). Nei gliomi di basso grado, l’rCBV nella massa (2,0±1,5) e nel margine (2,2±1,2) erano significativamente più bassi che nei gliomi di alto grado (p<0,001).ConclusioniIl PWI a 3T aiuta a differenziare la necrosi dalla massa tumorale, il tumore infiltrante dall’edema, e i gliomi di alto grado da quelli di basso grado. Esso facilita la caratterizzazione in RM dei gliomi cerebrali e fornisce utili informazioni per la pianificazione del trattamento chirurgico e radiante.

T2 relaxometry of brain in myotonic dystrophy.

Abstract We investigated the nature and extent of brain involvement in myotonic dystrophy (DM), examining possible T2 relaxation abnormalities in the brain of 20 patients with adult-onset DM and 20 sex- and age-matched normal controls. Brain MRI was performed at 0.5 T, and T2 values were calculated from signal intensity in two echoes. Regions of interest included: frontal, parietal, temporal, occipital and callosal (rostral and splenial) normal-appearing white matter; frontal, occipital, insular and hippocampal cortex; caudate nucleus, putamen, globus pallidus and thalamus. All white-matter and occipital and right frontal cortex regions showed a significantly longer T2 in the patients. Multiple regression analysis, including grey- and white-matter T2 as dependent variables, plus age at onset and at imaging, disease duration, muscular disability, brain atrophy and CTG trinucleotide repeats as independent variables, revealed that only white-matter T2 elongation and disease duration correlated positively. White-matter involvement in DM is more extensive than previously reported by MRI and neuropathological studies and seems to be progressive in the course of disease.

Guidelines on the clinical use for the detection of neutralizing antibodies (NAbs) to IFN beta in multiple sclerosis therapy: report from the Italian Multiple Sclerosis Study group

Interferon beta (IFNβ) was the first specific disease-modifying treatment licensed for relapsing-remitting multiple sclerosis, and is still one of the most commonly prescribed treatments. A strong body of evidence supports the effectiveness of IFNβ preparations in reducing the annual relapse rate, magnetic resonance (MRI) disease activity and disease progression. However, the development of binding/neutralizing antibodies (BAbs/NAbs) during treatment negatively affects clinical and MRI outcomes. Therefore, guidelines for the clinical use for the detection of NAbs in MS may result in better treatment of these patients. In October 2012, a panel of Italian neurologists from 17 MS clinics convened in Milan to review and discuss data on NAbs and their clinical relevance in the treatment of MS. In this paper, we report the panel’s recommendations for the use of IFNβ Nabs detection in the early identification of IFNβ non-responsiveness and the management of patients on IFNβ treatment in Italy, according to a model of therapeutically appropriate care.

Natalizumab vs interferon beta 1a in relapsing-remitting multiple sclerosis: a head-to-head retrospective study.

Background –  No head‐to‐head study has been performed yet to assess whether natalizumab is more effective than classical immunomodulators in multiple sclerosis (MS).

Search for compensation postures with videofluoromanometric investigation in dysphagic patients affected by amyotrophic lateral sclerosis

PurposeThis study was undertaken to verify the effectiveness of compensatory postures, suggested on the basis of the type of dysphagia identified at videofluoromanometric (VFM) investigation to ensure safe oropharyngeal transit.Materials and methodsEighty-one patients with amyotrophic lateral sclerosis (ALS) underwent speech therapy assessment and VFM investigation of the swallowing process. In the event of altered transit, penetration or aspiration of contrast material into the airways, compensation postures for correction of the swallowing disorder were suggested and verified during VFM examination.ResultsIn 37 patients, contrast agent transport was preserved and safe; in 19, we observed penetration of the contrast agent into the laryngeal inlet without aspiration; in 24, there was aspiration (four preswallowing, eight intraswallowing, nine postswallowing, three mixed), whereas in one patient no transit was seen. Penetration without aspiration was resolved by coughing or throat clearing; aspiration was resolved in 13 patients by assuming the chin-tuck posture and in six by rotating the head; in five patients, it was not resolved. A hyperextended head posture proved to be effective to resolve lack of transit.ConclusionsBy correlating morphological with functional data, VFM enables one not only to precisely characterise the dysphagic disorder but also to identify the most appropriate compensation posture for each patient and verify its effectiveness.RiassuntoObiettivoScopo del nostro lavoro è stato verificare l’efficacia delle posture di compenso, ipotizzate in base alle caratteristiche del disturbo disfagico individuato con videofluoromanometria (VFM), per garantire il transito orofaringeo in sicurezza.Materiali e metodiSono stati inclusi 81 pazienti affetti da sclerosi laterale amiotrofica (SLA) e sottoposti ad un protocollo di valutazione logopedia ed esame VFM della deglutizione. In caso di transito alterato, penetrazione o aspirazione del mezzo di contrasto (MdC) nelle vie aeree, sono state ipotizzate e verificate durante l’esame VFM posture di compenso per la correzione del disturbo deglutitorio.RisultatiIn 37 pazienti il transito del MdC era conservato e sicuro, in 19 abbiamo osservato penetrazione del MdC in aditus laringeo senza aspirazione, in 24 aspirazione (4 pre-deglutitoria, 8 intra-deglutitoria, 9 post-deglutitoria, 3 mista), in 1 non era presente transito. La penetrazione senza aspirazione è stata risolta con un colpo di tosse o col raclage sostenuto; l’aspirazione è stata risolta in 13 pazienti con la postura a capo flesso, in 6 col capo ruotato, in 5 non è stata risolta. Per l’assenza di transito è risultata efficace la postura a capo iperesteso.ConclusioniLa VFM, correlando il dato morfologico a quello funzionale, permette di caratterizzare con precisione il disturbo disfagico ed ipotizzare le posture di compenso più idonee al singolo caso e verificarne l’efficacia.

Natalizumab therapy of multiple sclerosis: recommendations of the Multiple Sclerosis Study Group—Italian Neurological Society

Three years after the introduction of natalizumab (NA) therapy for the second line treatment of relapsing-remitting multiple sclerosis (MS), Italian MS centers critically reviewed the scientific literature and their own clinical experience. Natalizumab was shown to be highly efficaciuos in the treatment of MS. However, the risk of progressive multifocal leukoencephalopathy was confirmed and defined better. This article summarizes the MS-SIN Study Group recommendations on the use of NA in MS, with particular reference to the appropriate selection and monitoring of patients as well as to the management of adverse events.

BDNF Val66Met polymorphism and brain volumes in multiple sclerosis

Brain derived neurotrophic factor (BDNF) regulates several CNS physiological and pathological processes. To investigate in multiple sclerosis (MS) patients, the relationship between the Val66Met polymorphism of BDNF and clinical markers of disease activity and MRI markers of focal and diffuse brain pathologies. 45 MS patients and 34 healthy controls (HCs) were genotyped and subjected to clinical-MRI examination. Global white matter fraction (gWM-f), gray matter-f (GM-f), cerebrospinal fluid-f (CSF-f), and abnormal WM-f were measured. We studied 26 Val/Val and 19 Val/Met patients and 23 Val/Val and 11 Val/Met HCs. We found that Val/Val patients had lower GM-f and higher CSF-f than Val/Val HCs; such differences were not statistically significant comparing Val/Met patients to HCs. The regression analysis showed that both Val/Met genotype and relapse number were associated with lower CSF-f. Our data suggest that Met allele might be a protective factor against MS as it is associated to a lower brain atrophy.