Author Of 1 Presentation
LB01.04 - Brain microstructural and metabolic alterations detected in vivo at the onset of the first demyelinating event.
Abstract
Background
In early multiple sclerosis, a clearer understanding of normal-brain tissue microstructural and metabolic abnormalities will provide valuable insights into its pathophysiology. Here, we studied the brain of patients with their first demyelinating episode using neurite orientation dispersion and density imaging (NODDI), for information about neuro-axonal density and spatial distribution, and 23Na MRI, for total sodium concentration reflecting neuro-axonal metabolic dysfunction and loss.
Objectives
To detect, using a multi-parametric quantitative MRI approach, clinically relevant alterations in the brain of early patients not captured by conventional MRI.
Methods
We enrolled 42 patients with clinically isolated syndrome or multiple sclerosis within 3 months from the onset and 16 healthy controls. We assessed physical and cognitive scales. On a 3T scanner, we acquired brain and spinal cord structural scans, and brain NODDI. Thirty-two patients and 13 healthy controls also underwent brain 23Na MRI. In the brain normal-appearing white matter, white matter lesions, and grey matter, we measured, from NODDI, the neurite density index (NDI), a marker of neuro-axonal density, and the orientation dispersion index (ODI), reflecting the fanning and crossing of neurites, and, from 23Na MRI, the TSC. We used linear regression models, adjusted for brain parenchymal fraction and lesion load, and Spearman correlation tests. For robust regression estimates, we used a p≤0.01.
Results
Patients showed higher ODI in normal-appearing white matter, including the corpus callosum, where they also showed lower NDI and higher TSC, compared with controls. In grey matter, compared with controls, patients had lower ODI in frontal, parietal and temporal cortex; lower NDI in parietal, temporal and occipital cortex; and higher TSC in limbic and frontal cortex. Brain volumes did not differ between patients and controls. In patients, higher ODI in corpus callosum was associated with worse performance on timed walk test (p=0.009, B=0.01, 99% Confidence Interval=0.0001-0.02), independent of brain and lesion volumes. Higher TSC in left frontal middle gyrus was associated with higher disability on Expanded Disability Status Scale (rs=0.5, p=0.005).
Conclusions
We found increased axonal dispersion in normal-appearing white matter, particularly corpus callosum, where we found also reduced axonal density and total sodium accumulation suggesting that this structure can be early affected by neurodegeneration. The association between increased axonal dispersion in the corpus callosum and worse walking performance implies that morphological and metabolic alterations in this structure may contribute to disability in multiple sclerosis. Brain volumes were neither altered nor related to disability in patients, so these two advanced MRI techniques can be more sensitive at detecting clinically relevant pathology in very early multiple sclerosis.
Author Of 1 Presentation
P0764 - A prognostically relevant functional-structural relationship in acute optic neuritis (ID 1569)
Abstract
Background
In the setting of acute optic neuritis (ON) it can be difficult to accurately predict clinical recovery and differentiate between the various associated syndromes.
Objectives
To prospectively investigate if comprehensive electrodiagnostic testing in acute optic neuritis (ON) can predict functional recovery or identify differences between ON subtypes.
Methods
Patients presenting with acute typical demyelinating ON and controls underwent pattern visual evoked potentials (PVEP), pattern electroretinography (PERG) and optical coherence tomography (OCT) within 14 days of symptom onset. OCT and visual acuity evaluation were repeated after approximately 3 months.
Results
We recruited 25 ON patients (11 isolated ON, 9 multiple sclerosis associated ON and 6 myelin-oligodendrocyte glycoprotein (MOG) seropositive ON) and 5 controls. All subjects were included acutely, with investigations done on average 6.7 days from first symptoms. Nine patients had conduction block at baseline. PVEP peak times were increased and amplitudes were decreased in ON. The PERGs showed that N95 and P50 amplitudes as well as P50 peak times were decreased in ON. None of the PVEP and PERG measures differed across the ON subtypes. A PVEP amplitude reduction was related to more severe GCL loss and thinner pRNFL layer at follow up (r=-0.58; p=0.008 and r=0.72; p=0.021). No such correlation existed at baseline. PVEP peak times and PERG measures were not similarly prognostic for structural outcome.
Conclusions
These data suggest that in acute ON, reduced neuronal function, as indirectly assessed by the reduced PVEP amplitudes, is predictive of subsequent neuronal loss. PVEP amplitudes may be helpful in guiding treatment decisions in acute ON.