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ObjectivesTo evaluate the frequency, clinical and etiologic features, and short- and long-term outcomes of early recurrent TIA.MethodsThis prospective observational cohort study enrolled all consecutive patients with TIA referred to our emergency department and diagnosed by a vascular neurologist. Expedited assessment and best secondary prevention were performed within 24 hours. Primary endpoints were stroke and a composite outcome including stroke, acute coronary syndrome, and vascular death at 3, 12, and, for a subset of patients, 60 months; secondary outcomes were TIA relapse, cerebral hemorrhage, new-onset atrial fibrillation, and death resulting from other causes. Concordance between index TIA and subsequent stroke etiologies was also evaluated.ResultsA total of 1,035 patients (822 with a single TIA, 213 with recurrent TIA = 21%) were enrolled from August 2010 to December 2017. Capsular warning syndrome and large artery atherosclerosis showed the strongest relationship with early recurrent TIA. The risk of stroke was significantly higher in the early recurrent TIA subgroup at each follow-up, and most stroke episodes occurred within 48 hours of index TIA. TIAs with lesion, dysarthria, and leukoaraiosis were the 3- and 12-month independent predictors of stroke incidence after early recurrent TIA subgroup. Index TIA and subsequent stroke etiologies showed substantial concordance. An ABCD3 score >6 predicted a higher risk of stroke recurrence over the entire follow-up.ConclusionsOur study evaluated long-term outcome after early recurrent TIA. Our observations support the importance of promptly detecting and treating patients with early recurrent TIAs to reduce the high early and long-term risk of poor clinical outcomes.

Background: Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease of the CNS in which a pathogenic role of anti-aquaporin-4 (AQP4) antibodies has been suggested. Although AQP4 is expressed in human cortex, recent histologic studies have failed to find any evidence of cortical demyelination in NMO. Objective: To evaluate, in vivo, the occurrence of focal and diffuse cortical pathology in NMO. Methods: We studied 30 patients with NMO, 30 patients with relapsing-remitting multiple sclerosis (RRMS), and 30 normal controls (NC). RRMS and NC were age- and gender-matched to NMO. The presence of cortical lesions (CLs) was evaluated on double inversion recovery sequence and cortical thickness (CTh) by the application of Freesurfer on 3 volumetric fast field echo T1-weighted images. Results: No CL was observed in NC or in NMO, while 83 CLs were identified in 20/30 (66.7%) patients with RRMS. Although NMO did not differ from NC in the global CTh, a mild thinning was observed in some cortical areas (postcentral [ p = 0.018], precentral [ p = 0.009], and calcarine [ p = 0.015] gyri) and in the thalamus ( p = 0.036). Global and regional cortical thickness was significantly decreased in RRMS compared to both NMO and NC. Discussion: Our in vivo data further suggest that the immune-mediated pathologic process occurring in NMO spares most of the cortex. NMO differs from multiple sclerosis, where CLs and atrophy are frequently found, even in early disease phases. Thus, MRI analysis of the cortex may be a potential diagnostic tool, especially in ambiguous cases.

Background: In primary progressive multiple sclerosis (PPMS), a discrepancy exists between the modest brain white matter (WM) lesion burden and the severity of neurologic disability. Double-inversion recovery (DIR) sequences have improved MRI sensitivity in the detection of cortical lesions (CLs) in patients with relapsing-onset MS. Objective: This 2-year longitudinal study was designed to assess the frequency, extent, and rate of formation of CLs in PPMS and their relationship with T2 lesion volume (LV), gray matter (GM) atrophy, and disability. Methods: Forty-eight patients with PPMS underwent clinical and magnetic resonance examinations at baseline and after 2 years. The number and volume of CLs, WM T2 LV, and GM fraction (GMf) were assessed at baseline and at follow-up. Results: At baseline, CLs were detected in 81.2% of patients with PPMS. At least one new CL was found in 28 patients during the follow-up. In patients with PPMS, CL and T2 WM LVs increased over the follow-up. At baseline, CL number and volumes were significantly correlated with T2 WM LV, GMf, disease duration, and Expanded Disability Status Scale score, as well as with increasing GM atrophy and disability during the follow-up. A multivariate analysis showed that CL volume at baseline was an independent predictor of percentage GM volume change and disability accumulation during the subsequent 2-year period. Conclusions: Cortical lesions are a frequent finding in primary progressive multiple sclerosis. The extent of such abnormalities is associated with the extent of cortical atrophy and clinical disability, and is able to predict their changes over a medium time period.

Although cognitive dysfunction affects a relevant portion of patients with multiple sclerosis (MS), its pathologic substrate has not been clarified and it does not seem entirely explained by white matter changes.A total of 100 consecutive patients with relapsing remitting MS (RRMS) and 42 normal controls (NC) were enrolled in the study. Cognitive performance was assessed by Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB). Regional cortical thickness (CTh) was evaluated by Freesurfer.Thirty-one patients with RRMS failed 1 or 2 tests of BRB and were considered to have a mild cognitive impairment (mCI-RRMS), while 8 patients failed at least 3 tests and were classified as markedly impaired (sCI-RRMS). The mean CTh of mCI-RRMS and sCI-RRMS group was significantly lower than in NC (p0.001) and cognitively normal patients with RRMS (CN-RRMS) (p0.001). The regional analysis revealed significant cortical thinning in frontal and temporal regions (frontotemporal thinning) of CN-RRMS compared to NC, while a widespread pattern of cortical thinning was observed in mCI-RRMS and in sCI-RRMS compared to both CN-RRMS and NC. A correlation was observed between cognitive score (CS) and the mean CTh (r = -0.69, p0.001) and between CS and CTh of almost all the cortical areas analyzed (r value between -0.20 and -0.65, p0.01). A correlation was found between T2-WM-LV and mean CTh (r = -0.31, p = 0.004) or CS (r = 0.21, p = 0.031). The multivariate analysis confirmed a widespread cortical thinning as the best predictor of cognitive impairment.A widespread pattern of cortical thinning characterizes patients with cognitive dysfunction, suggesting such dysfunction as expression of a more aggressive and widespread cortical pathology.

In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer9s disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1 year, both the treated and placebo groups worsened, but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, ideomotor and buccofacial apraxia, and selective attention. Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample. Reported adverse events were relatively mild, and there was no significant difference between the treated and placebo groups either in incidence or severity.