Author Topic: Black holes and MS prognosis  (Read 62 times)

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Offline agate

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Black holes and MS prognosis
« on: March 18, 2016, 07:23:31 pm »
From MedPage Today, March 18, 2016 [references omitted]:

Staring Into the Void: Black Holes and MS Prognosis[/color]

By Kara Nyberg, PhD
Reviewed by Kevin Hwang, MD, MPH

Research indicates that chronic T1 black holes reflect irreversible demyelination and axonal loss.

The number of black holes at baseline and their volume increase over time significantly predicts long-term disability.
Clinical studies that measure T1 black hole evolution may provide a deeper understanding of the ongoing disease process in MS and the possible effects of treatment.

Physicians commonly measure multiple sclerosis (MS) disease activity based on the appearance of new T2-weighted hyperintense MRI lesions, which arise due to edema, inflammation, gliosis, and axonal loss. Given the nonspecific disease processes leading to these lesions and the often-mediocre correlation between T2 lesions and clinical outcomes, however, the search continues for a more specific tool that lends insight into MS pathophysiology and disease activity.

In recent years, increasing attention has been paid to the possibility of measuring chronic or persistent T1-weighted lesions that appear hypointense relative to normal-appearing white matter—lesions also known as “black holes”—as a means of gauging MS-associated neurodegeneration. This approach is supported by a considerable body of histopathological evidence indicating that chronic T1 black holes reflect irreversible demyelination and axonal loss.

“In general, knowledge of the spatial localization and time evolution of T1-weighted lesions may help resolve some mysterious aspects of MS, which remains a largely unresolved pathology,” explained Khader M. Hasan, PhD, an Associate Professor of Radiology at the University of Texas Medical School at Houston, in an interview with MedPage Today.

Some consider the evolution of T1 lesions to be one of the most promising endpoints in phase 2 clinical trials of neuroprotective and reparative MS interventions.2 But despite this enthusiasm, a proven link between persistent black holes and clinical outcomes in MS remains elusive. Whereas a handful of studies have pinpointed a correlation between black hole volume and clinical disability as measured by the Expanded Disability Status Scale (EDSS), several others have failed to identify such ties.

To shed more light on whether black holes can be utilized to measure clinically relevant disease progression over time, lead investigator Nicola De Stefano, MD, PhD, an Associate Professor of Neurology at the University of Siena, Italy, and his colleagues conducted a longitudinal MRI study among a small group of 57 patients with confirmed relapsing-remitting MS for an average of 5 years. The investigators obtained brain scans of patients in 2000-2001 and again 10 years later using the same MRI protocol, thus ensuring comparable image quality at both time points. The scans were then compared to evaluate how patients’ brain lesions evolved over time and the impact of these changes on long-term disability, as measured using the EDSS.

The majority of patients—82%—experienced disease relapse over the 10-year study period, and the average EDSS score for the total cohort worsened from 1.8±1.1 (mean [SD]) at baseline to 2.5±1.7 after 10 years (P<.001). In tandem, over the 10-year follow-up period mean T2 lesion volume increased from 5.8 ±6.4 to 8.3±8.1 cm3 (P<.001), and mean T1 lesion volume from 2.4±3.6 to 4.4±5 cm3 (P<.001).

The investigators found that the long-term change in EDSS score was linked to the number of new and enlarging T1 and T2 lesions, as well as to increasing lesion volume. Notably, stepwise multiple regression analysis revealed that EDSS-measured declines in clinical disability best correlated with the combined measure of baseline T1 lesion count and increase in T1 lesion volume over time.3 Together, these factors explained 37% of the variability in worsening of the EDSS score over 10 years.

“The finding in our study that the number of black holes at baseline and their volume increase over time were the only significant brain lesion correlates of EDSS worsening over 10 years highlights the role of neurodegeneration in the pathophysiology of long-term disability in MS,” wrote Dr. De Stefano and colleagues about their results, published in the Multiple Sclerosis Journal.

Despite these findings, Dr. Hasan still views the relationship between T1 black holes and clinical measures of disease activity as tenuous. “Yes, black hole lesions are important, but other lesion types are also important. The lesion-centered approach in MS has not provided breakthrough insights into the pathogenesis of MS, as most MS lesions remain asymptomatic,” he commented.

One of Dr. Hasan’s biggest criticisms of the study is that the investigators provided no analysis of the possible effect of therapy. Fifty of the 57 patients received disease-modifying therapy during the study period, which makes it difficult to ascertain if and how much lesion evolution was influenced by the presence of treatment and the specific type of treatment. Phase 3 clinical studies that measure T1 black hole evolution may provide a deeper understanding of the ongoing disease process in MS and the possible effects of treatment.

These criticisms aside, Robert T. Naismith, MD, an Assistant Professor of Neurology at Washington University School of Medicine in St. Louis, believes that the findings from the recent Italian MRI study increase our understanding of T1 black holes in MS and may help inform treatment decisions. “The presence of black holes at baseline or their appearance during treatment should be one of several factors in predicting risk and may tip the decision toward either a first-line therapeutic with relatively high efficacy, or increased monitoring if an agent is chosen based primarily on established safety,” Dr. Naismith stated in a commentary on this study published in NEJM Journal Watch.
« Last Edit: March 18, 2016, 07:32:12 pm by agate »
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SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.


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