Introduction

Multiple sclerosis (MS) is a debilitating disease, last measured as affecting approximately 250,000 to 300,000 people in the United States¹. The primary hallmarks of this disease are most often damage to the protective white matter insulation around our brain cells, called myelin, and progressively worsening physiological deficits, such as muscle paralysis¹. The most precise MS diagnostic methods are a combination of analyzing cerebrospinal fluid and performing magnetic resonance imaging (MRI), although there is room for error when interpreting brain scan results². As a result, neurologists acknowledge there are some diseases which can be confused for MS, especially if similar lesions are found in myelin-rich areas^3,4,5,6,7. It is expensive to treat patients for a disease they do not have and ultimately harmful when their actual health condition goes undiagnosed and untreated^3,4. A recent study published in Multiple Sclerosis and Related Disorders by Kaisey et al. focused on a vein within brain scans which might hold the key to preventing future misdiagnoses of MS. This vein is called the central vein sign (CVS), because it can be found passing centrally through white matter lesions and serves as a marker which can be detected on MRI scans with an appropriate filter^8,9,10,11. Scientists found that when the CVS was used to analyze brain scans of patients both properly and misdiagnosed with MS, there was a large percent increase in the accuracy of correctly distinguishing patients with MS. Although use of the CVS was explored by other scientists^8,10, this study was the first to demonstrate its realistic clinical applications. Much of science takes place in the realm of the theoretical and the inside of a laboratory, but when discoveries are successfully applied in practice it lends credence to future studies.

Background

The CVS was initially discovered in a 2011 study performed by Tallantyre et al. which found that if a lesion was located on a visible vein within an MRI, it was likely to be in an area where myelin was damaged. The authors of this article stated the diagnostic marker had the potential to assist in correctly diagnosing MS, which many other studies have since explored^8,9,10,11. The specific diseases often misdiagnosed as MS are migraines, cerebral small vessel disease, neuromyelitis optica spectrum disorder, and inflammatory disorders like vasculitis^2,8. This is a wide range of disorders and reveals how a misdiagnosis can prevent many people from receiving the treatment they actually need. In order to differentiate between MS and other conditions, researchers have primarily focused on improving the quality of identification, including the creation of a computer-based approach involving machine learning which could eventually identify MS, if provided enough data for a framework to be established¹¹. The gradual successes yielded by prior studies have now allowed Kaisey et al. to explore the real world applications of using the CVS in correctly diagnosing MS. 

Methods

In order to properly assess whether or not MS was misdiagnosed, 15 people who were misdiagnosed with MS and 15 people who were correctly diagnosed with MS were given a specialized MRI called fluid-attenuated inversion recovery (FLAIR). This technique allows for the visualization of the CVS on an MRI scan, although to an unpracticed eye the result of this scan would likely be a brain with multiple lesions. Two unrelated clinicians with experience in CVS analysis were then given the scans and asked to perform lesion analysis in order to identify lesions with and without the CVS. Statistical analysis was then performed to determine the degree of reliability between clinicians and the accuracy of correctly distinguishing between MS and other diseases.

Results

The researchers found that when CVS analysis was used, 13 of the 15 misdiagnosed patient scans were correctly labeled as non-MS, for an accuracy rating of 87%². In other words, CVS analysis allowed for 87% more accurate diagnosis of MS patients while distinguishing between patients with other diseases. They also found that while there was not a notable difference in average lesions between both patient groups, there was a significantly higher average number of lesions with a CVS marker for correctly diagnosed MS patients. The two patients who continued to be misdiagnosed with MS had other comorbid health conditions thought to have contributed to CVS-positive lesions, such as a history of migraines. 

Discussion

The primary purpose of this study was to validate the use of an experimental technique in a clinical setting, and provide a strong foundation for future studies analyzing the CVS marker in MS patients. Kaisey et al. (2021) stated their study was unique because of its application to an extremely prevalent and realistic scenario of clinicians misdiagnosing a complicated neurological disease, and because of the success experienced by previous experimenters correctly diagnosing MS in theoretical scenarios. As previously stated, more research is currently being performed on CVS analysis, including a method of teaching automated identification of CVS-positive lesions to a machine learning program. Future studies could further validate the use of CVS analysis by expanding their sample sizes to include more patients in both groups. The limitations of this study, aside from smaller sample sizes, were the exclusion of lesions with multiple veins running through them. If a larger sample size was used there may have been less qualifying patients due to unanalyzable lesions. I thought this study had merit based not only off of the data found by these scientists, but also by the wealth of previous studies surrounding the topic. The use of scientific techniques to solve real world issues is a large endorsement of the time and money taken to develop the processes. The small sample size is an issue which plagues many clinical studies and will hopefully be remedied by future studies utilizing CVS analysis. 

[+] References

[+] Other Work By Susannah Schloss