Aquaporin-4 Immunoglobulin G–Seropositive Neuromyelitis Optica Spectrum Disorder MRI Characteristics: Data Analysis from the International Real-World PAMRINO Study Cohort

Research Background

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune central nervous system disease characterized by severe onset and relapse events, including optic neuritis, longitudinally extensive transverse myelitis (LETM), brainstem and/or hypothalamic syndromes, and encephalitis. Most patients have serum immunoglobulin G (IgG) antibodies against the astrocytic water channel Aquaporin-4 (AQP4). AQP4 protein is widely expressed in brain tissue, particularly in the brainstem, hypothalamus, and spinal cord. Therefore, AQP4-IgG-positive NMOSD patients typically exhibit lesions in these regions.

Although MRI plays a crucial role in the diagnosis and monitoring of NMOSD, existing MRI studies are mostly from small-scale or single-center studies, and there is a lack of internationally standardized imaging protocols. As a result, information on the regional distribution, frequency, and MRI enhancement related to acute attacks in NMOSD patients remains limited. To better understand the MRI characteristics of AQP4-IgG-positive NMOSD patients and evaluate the importance of MRI in disease monitoring, researchers conducted this large-scale international study.

Research Source

This study was led by Claudia Chien and her team at Charité-Universitätsmedizin Berlin and supported by the Guthy-Jackson Charitable Foundation International Clinical Consortium for NMOSD. The data were collected from 17 NMOSD expert centers across 11 countries, covering MRI and clinical data from August 2016 to January 2019. The results were published in 2024 in the journal Radiology, titled Aquaporin-4 Immunoglobulin G–Seropositive Neuromyelitis Optica Spectrum Disorder MRI Characteristics: Data Analysis from the International Real-World PAMRINO Study Cohort.

Research Process

Study Design and Participants

This retrospective study collected MRI and clinical data from 17 NMOSD expert centers worldwide. The study included 525 AQP4-IgG-positive NMOSD patients, of whom 320 underwent brain MRI, 152 underwent optic nerve MRI, 322 underwent upper spinal cord MRI, and 301 underwent lower spinal cord MRI. All patient MRI data were anonymized and independently reviewed by experienced neuroradiologists.

Data Collection and Analysis

The study used the Research Electronic Data Capture (REDCap) system to collect and organize clinical and MRI data. MRI data included T1-weighted, T2-weighted, and contrast-enhanced (CE) sequences. Researchers conducted detailed analyses of lesions in the brain, cerebellum, brainstem, optic nerve, optic chiasm, upper spinal cord, and lower spinal cord. Lesions were classified based on their anatomical location and imaging characteristics, such as longitudinally extensive transverse myelitis (LETM) and non-longitudinal extensive transverse myelitis (NETM).

Lesion Analysis

Researchers performed detailed visual assessments of each patient’s MRI lesions and classified them based on their location and characteristics. Brain lesions were primarily distributed in periventricular, subcortical, and cortical regions, while spinal cord lesions were mainly concentrated in the upper and lower spinal cord regions. Optic nerve lesions were predominantly found in the central and posterior regions, with many being bilateral. Contrast-enhanced lesions were most prominent within 15 days after an acute attack, particularly in the optic nerve and upper spinal cord regions.

Key Findings

Brain Lesions

Among the 320 patients who underwent brain MRI, 264 (82.5%) exhibited brain lesions. These lesions were primarily distributed in periventricular (81.1%) and subcortical regions (79.5%). Additionally, 17 patients (6.4%) exhibited tumefactive lesions, and 38 patients (14.4%) exhibited Dawson finger-like lesions. Contrast-enhanced lesions were observed in 42 of 245 patients (17.1%).

Optic Nerve Lesions

Among the 152 patients who underwent optic nerve MRI, 92 (60.5%) exhibited optic nerve lesions. These lesions were predominantly located in the central (88%) and posterior (86%) regions, with 39 patients (42%) exhibiting bilateral lesions. Contrast-enhanced lesions were observed in 47 of 92 patients (51%).

Spinal Cord Lesions

Among the 322 patients who underwent upper spinal cord MRI, 210 (65.2%) exhibited spinal cord lesions, with 133 (63.3%) exhibiting LETM and 105 (50%) exhibiting NETM. Among the 301 patients who underwent lower spinal cord MRI, 212 (70.4%) exhibited spinal cord lesions, with 149 (70.3%) exhibiting LETM and 84 (39.6%) exhibiting NETM. Contrast-enhanced lesions were observed in 87 of 242 patients (36%).

Conclusion

This study revealed the MRI characteristics of AQP4-IgG-positive NMOSD patients, confirming the high incidence of brain and spinal cord lesions. The study also found that non-longitudinal extensive transverse myelitis (NETM) is equally common in NMOSD patients, particularly in the upper spinal cord region. Additionally, contrast-enhanced lesions were most prominent within 15 days after an acute attack, particularly in the optic nerve and upper spinal cord regions. These findings provide important imaging evidence for the diagnosis and monitoring of NMOSD.

Research Highlights

  1. Large-Scale International Study: This study is the largest MRI feature analysis of AQP4-IgG-positive NMOSD patients to date, encompassing patient data from multiple countries worldwide.
  2. Lesion Distribution and Frequency: The study detailed the distribution and frequency of brain, optic nerve, and spinal cord lesions in NMOSD patients, providing important references for clinical diagnosis.
  3. Time Window for Contrast-Enhanced Lesions: The study found that contrast-enhanced lesions were most prominent within 15 days after an acute attack, particularly in the optic nerve and upper spinal cord regions, providing important evidence for imaging monitoring during the acute phase.
  4. High Incidence of Non-Longitudinal Extensive Transverse Myelitis (NETM): The study confirmed that NETM is equally common in NMOSD patients, particularly in the upper spinal cord region, challenging the previous view that LETM is the primary spinal cord lesion in NMOSD.

Research Significance

This study provides a comprehensive description of the MRI characteristics of AQP4-IgG-positive NMOSD patients, filling gaps in existing research. The findings not only help improve the diagnostic accuracy of NMOSD but also provide important imaging evidence for disease monitoring and treatment. Additionally, the study emphasizes the importance of internationally standardized MRI protocols, offering references for future multicenter studies.

Other Valuable Information

The study also found that brain lesions in NMOSD patients differ from those in multiple sclerosis (MS), particularly in lesion distribution and contrast enhancement characteristics. This finding helps differentiate NMOSD from MS, providing important evidence for clinical diagnosis. Furthermore, the study suggests that future research should further explore the pathological mechanisms of brain lesions in NMOSD patients, particularly their relationship with vascular risk factors.