Cortical lesion detection holds significant promise for refining prognosis in early multiple sclerosis (MS) by providing deeper insights into disease progression and potential disability outcomes. Unlike the more commonly recognized white matter lesions, cortical lesions occur in the brain’s outer layer, the cortex, and have historically been more challenging to detect with standard imaging techniques. However, advances in MRI technology and imaging protocols have increasingly allowed for better visualization of these lesions, revealing their widespread presence and strong association with clinical disability in MS.
Multiple sclerosis is a complex autoimmune disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Traditionally, diagnosis and prognosis have relied heavily on detecting white matter plaques visible on MRI scans. These plaques are typically ovoid and perivenular, scattered throughout the brain and spinal cord. While white matter lesions are critical markers, they do not fully explain the variability in clinical outcomes seen among patients, especially in the early stages of the disease.
Cortical lesions represent a distinct pathological feature that contributes to the disease burden in MS. They are often linked to more severe physical disability and cognitive impairment, which are not always predicted by white matter lesion load alone. Detecting these lesions early can therefore provide a more nuanced understanding of disease activity and progression. This is particularly important because MS progression involves not only relapses and new lesion formation but also subtle, ongoing neurodegeneration that may be silent initially but leads to irreversible disability over time.
The challenge with cortical lesions has been their subtle appearance on conventional MRI sequences. They are smaller, less inflammatory, and often lack the contrast enhancement seen in active white matter lesions, making them harder to identify. Recent improvements in MRI techniques, such as high-resolution 3D FLAIR and specialized sequences like double inversion recovery (DIR), have enhanced the sensitivity for detecting cortical lesions. Additionally, advanced imaging modalities like susceptibility-weighted imaging (SWI) and ultra-high-field MRI scanners (7 Tesla) have further improved lesion visualization, enabling clinicians and researchers to detect these lesions earlier and more reliably.
Identifying cortical lesions early in the disease course can refine prognosis by highlighting patients at greater risk for rapid progression and disability accumulation. Studies have shown that patients with a higher cortical lesion burden tend to experience faster cognitive decline and physical disability progression. This information can be crucial for tailoring treatment strategies, as early aggressive therapy might be warranted in patients with extensive cortical involvement to slow down neurodegeneration and preserve neurological function.
Moreover, cortical lesions are thought to reflect a different pathological process compared to white matter lesions. They may indicate more chronic, smoldering inflammation and neurodegeneration rather than acute inflammatory attacks. This distinction is important because it suggests that cortical lesions could serve as biomarkers for the neurodegenerative component of MS, which is less responsive to conventional anti-inflammatory treatments. Understanding this aspect of the disease could lead to the development of new therapeutic approaches targeting neuroprotection and repair.
In addition to physical disability, cortical lesions have been linked to cognitive impairment in MS. Cognitive dysfunction affects a significant proportion of patients and can severely impact quality of life. Lesion-driven disconnection of neural networks, particularly involving the cortex, disrupts cognitive processing. Therefore, detecting cortical lesions provides valuable prognostic information about potential cognitive decline, allowing for earlier interventions such as cognitive rehabilitation or supportive therapies.
The integration of cortical lesion detection into routine clinical practice faces some hurdles. High-resolution imaging protocols require longer scan times and more specialized equipment, which may not be widely available. Interpretation of cortical lesions also demands expertise, as these lesions can be subtle and easily overlooked. Nonetheless, as imaging technology becomes more accessible and standardized protocols are developed, cortical lesion detection is poised to become a critical component of MS diagnosis and prognosis.
Beyond imaging, combining cortical lesion data with other biomarkers—such as fluid biomarkers indicating astrocytic damage or neurodegeneration—could further enhance prognostic accuracy. For example, elevated levels of glial fibrillary acidic protein (G
