Prospective Assessment of No Evidence of Disease Activity-4 Status in Early Disease Stages of Multiple Sclerosis in Routine Clinical Practice.

Background: In relapsing-remitting multiple sclerosis, no evidence of disease activity-3 (NEDA-3) is defined as no relapses, no disability progression and no MRI activity. NEDA-4 status is defined as meeting all NEDA-3 criteria plus having an annualized brain volume loss (a-BVL) of ≤0.4%. Prospective real-world studies presenting data on NEDA-4 are scarce. Objective: To determine the proportion of patients failing to meet one or more NEDA-4 criteria and the contribution of each component to this failure. Methods: Forty-eight patients were followed for 12 months. Structural image evaluation, using normalization, of atrophy was used to assess a-BVL. Results: The patients had a mean age of 33.0 years (range 18-57), disease duration of 1.7 years (0.4-4) and Expanded Disability Status Scale score of 1.3 (0-4); 71% were women. All patients were on disease-modifying therapies. During follow-up, 21% of the patients had at least one relapse, 21% had disability progression, 8% had new T2 lesions, and 10% had gadolinium-enhanced lesions. Fifty-eight percent (28/48) achieved NEDA-3 status. a-BVL of >0.4% was observed in 52% (25/48). Only 29% (14/48) achieved NEDA-4 status. Conclusion: a-BVL is a good marker to detect subclinical disease activity. a-BVL is parameter to continue investigating for guiding clinical practice in relapsing-remitting multiple sclerosis.

Self-reported urinary impairment identifies 'fast progressors' in terms of neuronal loss in multiple system atrophy.

INTRODUCTION: MSA is an adult-onset, sporadic, progressive parkinsonian syndrome characterised by the presence of akinesia, cerebellar dysfunction, autonomic failure and pyramidal signs. Annualized-whole-brain atrophy rate (a-WBAR) is an informative way to quantify disease progression. In this longitudinal work we investigate the correlations of a-WBAR with clinical scales for motor impairment, autonomic disability and cognitive decline in MSA and explore how atrophy progresses within the brain. METHOD: Fourty-one MSA patients were studied using Structural Imaging Evaluation with Normalization of Atrophy (SIENA). SIENA is an MRI-based algorithm that quantifies brain tissue volume. Clinical parameters were explored using the 18-item Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale, the Hoehn and Yahr Scale, the Frontal Assessment Battery and the Natural History and Neuroprotection in Parkinson Plus Syndromes scale (sub-items for orthostatic and urinary functions). RESULTS: The mean (±SD) age was 60.4 years ±â€¯7.7 and a-WBAR was 1.65% ±â€¯0.9. Demographics and clinical ratings at the time of the first scan were non-significantly associated with a-WBAR. The only exception was the baseline urinary score with a weak but significant association (R2 = 0.15, p = 0.04). Progression of grey matter atrophy was detected in the left superior temporal gyrus, right middle frontal gyrus, right frontopolar region and midbrain. CONCLUSION: Urinary impairment at baseline may help to identify 'fast progressors' in terms of neuronal loss, particularly in the frontal and temporal lobes. Thus, urinary impairment should be recognized as a key target for disease modifying therapeutic interventions in MSA.

NOTCH 1 Mutation in a Patient with Spontaneous and Recurrent Dissections of Extracranial Arteries.

Dissections of extracranial arteries are estimated to account for only 2% of all ischemic strokes but for approximately 20% of strokes in patients younger than 45 years old. Most dissections of extracranial arteries involve some trauma stretch, mechanical stress, or connective tissue abnormalities. In the absence of these disorders, determining the etiology of recurrent extracranial dissections is quite challenging because the underlying nature of these cases is poorly understood. We report the case of a 44-year-old female with recurrent dissections of the vertebral and carotid arteries associated with a heterozygous mutation p.Pro2122Leu in the NOTCH 1 gene. Her mother with a thoracic aortic aneurysm was also positive for this variant.

Retrospective Diagnosis of Parkinsonian Syndromes Using Whole-Brain Atrophy Rates.

Objective: The absence of markers for ante-mortem diagnosis of idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) results in these disorders being commonly mistaken for each other, particularly in the initial stages. We aimed to investigate annualized whole-brain atrophy rates (a-WBAR) in these disorders to aid in the diagnosis between IPD vs. PSP and MSA. Methods: Ten healthy controls, 20 IPD, 39 PSP, and 41 MSA patients were studied using Structural Imaging Evaluation with Normalization of Atrophy (SIENA). SIENA is an MRI-based algorithm that quantifies brain tissue volume and does not require radiotracers. SIENA has been shown to have a low estimation error for atrophy rate over the whole brain (0.5%). Results: In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17-0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32-0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.93% ± 1.1 (CI 95% 1.5-2.2). In MSA a-WBAR was 1.65% ± 0.9 (CI 95%1.37-1.93). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in IPD (p < 0.001). a-WBAR 0.6% differentiated patients with IPD from those with PSA and MSA with 91% sensitivity and 80% specificity. Conclusions: a-WBAR within the normal range is unlikely to be observed in PSP or MSA. a-WBAR may add a potential retrospective application to improve the diagnostic accuracy of MSA and PSP vs. IPD during the first year of clinical assessment.