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Use Of The Brain Parenchymal Fraction To Measure
Whole Brain Atrophy In Relapsing/Remitting MS

Multiple Sclerosis Collaborative Research Group
Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L
Neurology 1999; 53:1698-704
Cleveland Clinic Foundation, Dept of Neurology, Cleveland, OH 44195, USA
PMID# 10563615; UI# 20025139
Abstract

Background
Episodic inflammation in the CNS during the early stages of MS results in progressive disability years later, presumably due to Myelin and Axonal injury.

MRI demonstrates ongoing disease activity during the early disease stage, even in some patients who are stable clinically. The optimal MRI measure for the destructive pathologic process is uncertain, however.

Methods
In this post-hoc study, MRI scans were analyzed from patients with Relapsing MS participating in a placebo-controlled trial of Interferon-ß-1a (Avonex).

The Brain Parenchymal Fraction, defined as the ratio of Brain Parenchymal Volume to the total volume within the Brain surface contour, was used to measure whole Brain Atrophy that had occurred, calculated as the loss of Brain tissue volume relative to the Cranial volume.

The MRI scans were analyzed using a new special image analysis method called Brain Parenchymal Fraction (BPF). BPF calculates the amount of Brain tissue in the skull as a ratio of skull volume.

Upon study entry, the baseline MRIs showed a significantly reduced BPF in the MS patients when compared to 16 healthy controls, indicating significant Brain Atrophy at entry into the study.

The placebo-controlled group showed a significant reduction in BPF - or increased loss of Brain tissue - during the first year (-0.75 percent) and second year (-0.53 percent) of observation.

Avonex treatment (30 mcg injected intramuscularly once a week) had no effect on Brain Atrophy during the first year of observation; however, there was a statistically significant 55 percent reduction in the rate of Atrophy compared with placebo recipients during the second year.

The relationship between disease features and Brain Atrophy and effect of Interferon-ß-1a were determined.

Results
MS patients had significant Brain Atrophy that worsened during each of 2 years of observation. In many patients, Brain Atrophy worsened without clinical disease activity.

Baseline clinical and MRI abnormalities were not strongly related to the rate of Brain Atrophy during the subsequent 2 years.

Treatment with Interferon-ß-1a resulted in a reduction in Brain Atrophy progression during the second year of the clinical trial.

Conclusions
Patients with Relapsing/Remitting MS have measurable amounts of whole Brain Atrophy that worsens yearly, in most cases without clinical manifestations.

The Brain Parenchymal Fraction is a marker for destructive pathologic processes ongoing in Relapsing MS patients, and appears useful in demonstrating treatment effects in controlled clinical trials.



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