Differential diagnosis of suspected multiple sclerosis: a consensus approach

BACKGROUND AND OBJECTIVES: Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. METHODS: Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. RESULTS: We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of "clinically isolated syndromes" (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. CONCLUSIONS: Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision

Quantitative brain volumetric analysis from patients with multiple sclerosis: A follow-up study

none6noInglese, M; Rovaris, M; Giacomotti, L; Mastronardo, G; Comi, G; Filippi, M.Inglese, MARIA MATILDE; Rovaris, M; Giacomotti, L; Mastronardo, G; Comi, G; Filippi, M

N,N,N',N'-Polybenzylated alicyclic 1,2-diamines: cytotoxicity and G1 phase arrest in cancer cell line

Cytotoxicity in the mu M range was observed in cancer cell lines treated with N,N,N',N'-tetrabenzyl-4,5-diamino-2-cyclopentenone. Cell cycle analysis on HeLa cells showed a clear G1 phase arrest. A preliminary SAR on structural analogs was performed in order to identify the pharmacophores

Short-term evolution of new multiple sclerosis lesions enhancing on standard and triple dose gadolinium-enhanced brain MRI scans.

We compared the short-term magnetic resonance imaging (MRI) evolution of new multiple sclerosis (MS) lesions enhancing after single dose (SD) (0.1 mmol/kg) or triple dose (TD) (0.3 mmol/kg) gadolinium-DTPA (Gd) to explore possible differences in the pathological substrates of acute MS lesions. Brain MRI scans were obtained at baseline and every 4 weeks for a 3-month period in 18 relapsing-remitting MS patients. At each time point, using two separate sessions, we obtained dual echo and T1-weighted scans before and after SD and TD of Gd. New enhancing lesions detected at month 1 and 2 were entered into the analysis. The presence of corresponding hypointense lesions on unenhanced T1-weighted scans and hyperintense lesions on T2/proton density (PD)-weighted images was assessed on the same scan and on the scans performed 1 month before and 1 month after the new lesion development. Persistence of enhancement was evaluated on the SD and TD scans obtained 1 month after new lesion appearance. One-hundred and sixty lesions were studied. Of these, 97 lesions were enhancing after both SD and TD (group A) and 63 lesions only after TD (group B). Thirty (31\%) of the lesions enhancing after both SD and TD and ten (16\%) of the lesions enhancing only after TD had corresponding T1-weighted lesions (P = 0.03). Of these lesions, 87\% in group A and 40\% in group B (P = 0.003) were not hypointense on the previous scans. No differences were found in the frequencies of corresponding T2/PD-weighted abnormalities (92\% in Group A vs. 87\% in Group B lesions). Of these hyperintense areas, 62\% in group A and 56\% in group B were not present on the previous scans. On follow-up scans, 52\% of the lesions enhancing after SD and TD and 70\% of the lesions enhancing only after TD did not show enhancement after the injection of both the doses of Gd (P = 0.02). The frequencies of corresponding T2/PD and T1-weighted abnormalities were higher in Group A than in Group B lesions, but the differences were not statistically significant. Our findings suggest that the pathological process is less severe in MS lesions enhancing only after TD injection than in those enhancing after the SD

Comparison of Three MR Sequences for the Detection of Cervical Cord Lesions in Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE: Improving the sensitivity of MR imaging for the detection of multiple sclerosis (MS) lesions in the cord might be useful in the diagnostic workup and could lead to a better understanding of the evolution of the disease. The purpose of this study was to compare fast spin-echo (FSE) with magnetization transfer–prepared gradient-echo (MT-GE) and fast short-inversion-time inversion recovery (fast-STIR) MR sequences to determine which is best for imaging cervical cord lesions in MS patients. METHODS: FSE, MT-GE, and fast-STIR MR images were obtained in 56 MS patients and 10 healthy control subjects with a 1.5-T MR system and a phased-array coil. Cord lesions seen on images obtained with each sequence were counted by two observers in two stages (stage 1: random review of the complete sets of images from each technique; stage 2: side-by-side review with a retrospective count of lesions). RESULTS: At the end of stage 1, a mean of 1.16 cord lesions per patient were seen on FSE images, 1.57 on MT-GE images (35% more than on FSE), and 1.92 on fast-STIR images (66% more than on FSE). Two or more cervical cord lesions were found on 16 FSE images (29%), 23 on MT-GE images (46%), and 30 on fast-STIR images (54%). Differences were reduced after stage 2: MT-GE detected 22% more lesions and fast-STIR 36% more lesions than FSE. Considering the three sequences together, 113 cervical cord lesions were seen in 50 patients (89%). CONCLUSION: Both MT-GE and fast-STIR sequences depict more cervical cord MS lesions than the FSE sequence, with fast-STIR having the best sensitivity. Fast-STIR MR images may be useful for the diagnostic workup of patients with suspected MS and for improving our understanding of the evolution of MS