Faculty Bibliography

BACKGROUND:In neuromyelitis optica spectrum disorder (NMOSD), clinical disability in NMOSD patients is relapse-related and progressive phase is rare. This observation raises the question whether there is any radiographic disease activity. The aim of present study was to determine the longitudinal changes in cerebral lesion number, lesion size, lesion-to-venule relationship, and morphological patterns of lesions in NMOSD using multiparametric 7T MR imaging. We also aimed to assess brain volume changes in NMOSD. METHODS:A cohort of 22 patients with NMOSD underwent high-resolution 3D-susceptibility weighted imaging (SWI) and 2D-gradient-echo (GRE-T2*) weighted imaging on 7T MRI of brain at baseline and after ~2.8 years of follow-up. Morphologic imaging characteristics, and signal intensity patterns of lesions were recorded at both time points. Lesions were classified as "iron-laden" if they demonstrated hypointense signal on GRE-T2* images and/or SWI as well as hyperintense signal on quantitative susceptibility mapping (QSM). Lesions were considered "non-iron-laden" if they were hyperintense on GRE-T2*/SWI and isointense or hyperintense on QSM. Additionally, fractional brain parenchymal volume (fBPV) was computed at both time points. RESULTS:A total of 169 lesions were observed at baseline. At follow-up, 6 new lesions were found in 5 patients. In one patient, a single lesion could not be detected on the follow-up scan. No appreciable change in lesion size and vessel-lesion relationship was observed at follow up. All lesions demonstrated hyperintense signal intensity on GRE-T2* weighted images and isointense signal on QSM at both time points. Therefore, these lesions were considered as non-associated with iron pathology. Additionally, no significant change in brain volume was observed: fBPV 0.78 ± 0.06 at baseline vs. 0.77 ± 0.05 at follow up, p>0.05. CONCLUSION/CONCLUSIONS:Cerebral lesions in NMOSD patients remain 'inert' and do not show any substantial variations in morphological characteristics during a 2-3-year follow-up period.

OBJECTIVE:To determine if the concentration and saturation of natalizumab (NTZ) administration at extended interval dosing (EID; every 5-8 weeks) over 18 months is able to be maintained in the range considered adequate to sustain the clinical efficacy of NTZ. METHODS:-integrin receptor saturations were analyzed via cytometry, in blood samples obtained at trough timepoints. RESULTS:Trough serum concentration was above the "therapeutic" concentration of 2.0 μg/mL in 72% of EID patients. Trough saturation was above the "therapeutic" 50% threshold in 79% of EID-treated patients. Our model predicted that at least 9 NTZ infusions/year are required to maintain adequate trough saturation and concentration levels. Higher body mass index (BMI) was a predictor of suboptimal trough saturation on EID NTZ. CONCLUSIONS:Trough α4-integrin receptor saturation >50% correlated with high clinical efficacy of NTZ in previous studies. A continual treatment with EID maintains receptor saturation and concentration that are in the "therapeutic range" for most patients. This finding provides biological plausibility for the clinical efficacy of NTZ EID. Patients with higher BMI may require closer clinical and MRI follow-up.

Severity score represents disease duration-adjusted mean rank of disability in multiple sclerosis (MS) patients from the reference population. This measure allows one to compare the relative rates of disease progression among patients, patient subgroups, and across epochs, which opens up new question of what accounts for the observed differences in severity, and can be used to assess correlation between disease severity and clinical, radiologic, immunologic, genetic, and environmental variables of interest. Severity score can also prove useful for developing prognostic tools in MS. This article discusses the diverse applications of severity score concept in MS research, and (re)introduces Herbert's proposal of severity-based MS classification in the context of variability of MS severity.

BACKGROUND:Spinal epidural lipomatosis (SEL) is a rare condition defined as pathological overgrowth of the normally present epidural fat within the spinal canal. SEL is associated with Cushing disease, obesity and chronic corticosteroid therapy. Diabetes mellitus type 1 (DM1) has not known to be a risk factor for SEL. The neurological symptoms of SEL are attributed mainly to mechanical compression on the spinal cord and the cauda equina. METHODS:A retrospective chart review of patients evaluated at NYU Multiple Sclerosis Care Center identified three diabetic patients with progressive myelopathy associated with SEL. We report the clinical course, diagnostic workup and outcomes in these three patients with SEL-associated myelopathy. RESULTS:Three patients (2 females and 1 male) had long-standing DM1 and developed progressive myelopathy in their early 40's. All were found to have thoracic SEL (extensive extradural T1, T2 hyperintense signal; biopsy confirmed in one case) with associated extensive abnormal cord signal in lower cervical/upper thoracic spinal cord. A comprehensive evaluation for metabolic, infectious, autoimmune and vascular causes of myelopathy that included serologies, cerebrospinal fluid analyses, and spinal angiography did not reveal an alternative cause for myelopathy. One of the patients underwent a surgical decompression of SEL with subsequent clinical and radiologic improvement. CONCLUSIONS:Our case series suggest that patients with DM1 and myelopathy of unknown cause should be evaluated for SEL. Timely diagnosis and appropriate intervention may forestall progression of neurological disability and even result in neurologic improvement. SEL should be considered on the short list of diagnoses that cause potentially reversible progressive myelopathy.