Natalizumab versus fingolimod in patients with relapsing-remitting multiple sclerosis non-responding to first-line injectable therapies.

BACKGROUND: Natalizumab and fingolimod have not been compared in controlled trials but only in observational studies, with inconclusive results. OBJECTIVES: The objective of this study is to compare the effect of natalizumab and fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). METHODS: We included all consecutive RRMS patients switched from first-line agents (glatiramer acetate/interferons) to natalizumab or fingolimod, with a follow-up of 24 months. Data of relapses, Expanded Disability Status Scale score and brain magnetic resonance imaging (MRI) scans were collected. We used propensity score (PS) matching and intention-to-treat analysis. RESULTS: We retained 102 patients in each cohort after PS matching, with similar baseline characteristics. More patients discontinued natalizumab compared to fingolimod (33% vs 11%, p < 0.001), mainly for progressive multifocal leukoencephalopathy (PML) concern. No serious adverse events occurred in the two cohorts. Compared to fingolimod, the natalizumab group presented a higher percentage of relapse-free patients (66% vs 80%, p = 0.015), a higher percentage of disability-improved patients (6% vs 15%, p = 0.033), a lower percentage of MRI-active patients (38% vs 14%, p = 0.001) and a higher percentage of patients with no evidence of disease activity (NEDA-3; 44% vs 70%, p < 0.001) after 2 years of follow-up. Disability worsening was not statistically different in the two groups. CONCLUSION: Natalizumab is superior to fingolimod in RRMS patients non-responding to first-line agents.

Guidelines from The Italian Neurological and Neuroradiological Societies for the use of magnetic resonance imaging in daily life clinical practice of multiple sclerosis patients.

MRI is highly sensitive in detecting focal white matter lesions in multiple sclerosis (MS). For this reason, it has been formally included in the diagnostic workup of patients with clinically isolated syndromes suggestive of MS, through the definition of ad hoc sets of criteria to show disease dissemination in space and time. MRI is used in virtually all clinical trials of the disease as a surrogate measure of treatment response. Several guidelines have been published to help characterizing the imaging features on conventional MR sequences of "typical" MS lesions and work has also been performed to identify "red flags" which should alert the clinicians to exclude possible alternative conditions. Despite this, the application of the available guidelines and criteria in daily life clinical practice is still limited and varies among and within countries (including Italy) due to regulatory issues and heterogeneity of MRI facilities. It is crucial for neurologists and neuroradiologists to become familiar with these criteria to improve the quality of their diagnostic assessment. In patients with established MS, the main problem is to define standard procedures for monitoring the course of the disease and treatment response. This review aims at providing daily life guidelines to clinicians for a correct application of MRI in the workup of patients suspected of having MS as well as in the monitoring of disease evolution in those with established MS. It also offers clues for the standardization of MRI studies and relative reporting to be applied at a national level.

The Italian Brain Normative Archive of structural MR scans: norms for medial temporal atrophy and white matter lesions.

BACKGROUND AND AIMS: To describe the clinical and neuropsychological features of a large group of cognitively intact persons subjected to brain high-resolution magnetic resonance (MR), to compare them with the general population, and to set norms for medial temporal atrophy and white matter lesions. METHODS: Participants in the Italian Brain Normative Archive (IBNA) study were 483 consecutive volunteers undergoing MR for reasons unrelated to cognition (migraine or headache, visual and balance or auditory disturbances, paresthesias, and others) and showing no brain damage. Manual tracing of hippocampal and amygdalar volumes and visual rating of white matter lesions were made. The whole study group was stratified by age (

Imaging of cranio-meningeal infectious and inflammatory involvement.

A pictorial review was performed (with added acquisition technique optimization guidelines) on CT and MR imaging of intracranial meningeal involvement from infectious or inflammatory origin, on the inherent main differential diagnoses, and on the topography of contiguous extension of lesions.

Complications of migraine: migrainous infarction.

Migraine and cerebrovascular disorders are comorbid diseases and the overlap of their clinical symptoms has relevant diagnostic and therapeutic implications. The prototypic condition of this relationship is reproduced by a clinical event named migrainous infarction (MI), listed by the ICHD-II among the "complication of migraine." We discuss the diagnostic criteria proposed for this rare condition with regard to the epidemiological studies and the clinicopathogenetic implications. In the clinical setting therefore, "possible" cases of migrainous infarction should undergo an extended diagnostic workup to rule out symptomatic migraine due to extra/intra-cranial vascular pathology (artery dissection/malformations, venous thrombosis) and to exclude a causal role for other conditions. These include patent foramen ovale and thrombophylic status that may become critical risk factors for stroke, particularly among migraineurs, in coincidence with precipitating factors that should be more accurately considered in each single case.

Brain volumes in healthy adults aged 40 years and over: a voxel-based morphometry study.

BACKGROUND AND AIMS: Gender and age effect on brain morphology have been extensively investigated. However, the great variety in methods applied to morphology partly explain the conflicting results of linear patterns of tissue changes and lateral asymmetry in men and women. The aim of the present study was to assess the effect of age, gender and laterality on the volumes of gray matter (GM) and white matter (WM) in a large group of healthy adults by means of voxel-based morphometry. This technique, based on observer-independent algorithms, automatically segments the 3 types of tissue and computes the amount of tissue in each single voxel. METHODS: Subjects were 229 healthy subjects of 40 years of age or older, who underwent magnetic resonance (MR) for reasons other than cognitive impairment. MR images were reoriented following the AC-PC line and, after removing the voxels below the cerebellum, were processed by Statistical Parametric Mapping (SPM99). GM and WM volumes were normalized for intracranial volume. RESULTS: Women had more fractional GM and WM volumes than men. Age was negatively correlated with both fractional GM and WM, and a gender x age interaction effect was found for WM, men having greater WM loss with advancing age. Pairwise differences between left and right GM were negative (greater GM in right hemisphere) in men, and positive (greater GM in left hemisphere) in women (-0.56+/-4.2 vs 0.99+/-4.8; p=0.019). CONCLUSIONS: These results support side-specific accelerated WM loss in men, and may help our better understanding of changes in regional brain structures associated with pathological aging.