Disruption of the leptomeningeal blood barrier in neuromyelitis optica spectrum disorder

Abstract

Objective: To describe leptomeningeal blood-barrier impairment reflected by MRI gadolinium-enhanced lesions in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD).

Methods: A retrospective case series of 11 AQP4-IgG-positive NMOSD patients with leptomeningeal enhancement (LME) were collected from 5 centers. External neuroradiologists, blinded to the clinical details, evaluated MRIs.

Results: LME was demonstrated on postcontrast T1-weighted and fluid-attenuated inversion recovery images as a sign of leptomeningeal blood-barrier disruption and transient leakage of contrast agent into the subarachnoid space in 11 patients, 6 in the brain and 6 in the spinal cord. The patterns of LME were linear or extensive and were accompanied by periependymal enhancement in 5 cases and intraparenchymal enhancement in all cases. The location of LME in the spinal cord was adjacent to intraparenchymal contrast enhancement with involvement of a median number of 12 (range 5-17) vertebral segments. At the time of LME on MRI, all patients had a clinical attack such as encephalopathy (36%) and/or myelopathy (70%) with median interval between symptom onset and LME of 12 days (range 2-30). LME occurred in association with an initial area postrema attack (44%), signs of systemic infection (33%), or AQP4-IgG in CSF (22%) followed by clinical progression. LME was found at initial clinical presentation in 5 cases and at clinical relapses leading to a diagnosis of NMOSD in 6 cases.

Conclusion: This study suggests that altered leptomeningeal blood barrier may be accompanied by intraparenchymal blood-brain barrier breakdown in patients with AQP4-IgG-positive NMOSD during relapses.

Figure 1. Leptomeningeal enhancement accompanied by intraparenchymal enhancement during attacks in patients with NMOSD

Contrast-enhanced cerebral T1W (A.a, A.b, B.b, C.a, and C.b), FLAIR sequences (A.c, B.a, B.c, and C.c) and FLAIR post–contrast-enhanced image (B.a) MRI from 3 patients with AQP4-IgG–positive NMOSD (A, B, and C) during attacks, showing leptomeningeal enhancement (A.a, A.b, B.a, C.a, and C.b), marked with arrows. Parenchymal lesions are seen including cloud-like enhancement (B.c, A.c, and C.c). Notably, enhancement occurred at the ependymal surface of the lateral ventricles (B.a). AQP4-IgG = aquaporin-4 immunoglobulin G; FLAIR = fluid-attenuated inversion recovery; NMOSD = neuromyelitis optica spectrum disorder; T1W = T1 weighted.

Figure 2. LETM in association with leptomeningeal enhancement

Sagittal (A.a and B.a) and axial (A.c and B.c) T1W contrast-enhanced images and sagittal T2W (A.b and B.b) and axial images (A.d and B.d) of spinal cord MRI from 2 (A and B) AQP4-IgG–positive patients with NMOSD. Images were obtained during acute LETM attacks with leptomeningeal and intraparenchymal (A.a and A.c at th10; B.a and B.c at th12) T1W contrast enhancement. The spinal cord lesions were also demonstrated on T2W and STIR images (A.b, A.d, B.b, and B.d). AQP4-IgG = aquaporin-4 immunoglobulin G; LETM = longitudinally extensive transverse myelitis; NMOSD = neuromyelitis optica spectrum disorder; STIR = short tau inversion recovery; T1W = T1 weighted; T2W = T2 weighted.

Figure 3. An area postrema lesion in association with leptomeningeal enhancement and intraparenchymal BBB breakdown

Spinal cord MRI (A–C) and brain MRI (D–G) from an AQP4-IgG–positive patient with NMOSD who presented with recurrent myelopathy of 1 month duration and area postrema lesion, which progressed into LETM. Images were obtained during acute attacks. An area postrema lesion (A) in association with subacute progression to LETM with leptomeningeal and intraparenchymal T1W contrast enhancement (arrows, B). The spinal cord lesions were also demonstrated on T2W and STIR images (C). Cerebral MRI during another attack with periependymal enhancement on T1W images at the lateral (D) and third ventricles (F). FLAIR images showing lesions along lateral ventricle (E), thalamus, and hypothalamus (G). (B) Used with permission of the publisher from Flanagan EP, Weinshenker BG. Neuromyelitis optica spectrum disorders. Curr Neurol Neurosci Rep 2014;14:483. Copyright © 2014, Springer Science+Business Media New York. AQP4-IgG = aquaporin-4 immunoglobulin G; BBB = blood-brain barrier; FLAIR = fluid-attenuated inversion recovery; LETM = longitudinally extensive transverse myelitis; NMOSD = neuromyelitis optica spectrum disorder; T1W = T1 weighted; T2W = T2 weighted.

Figure 4. Leptomeningeal enhancement in association with the presence of AQP4-IgG in CSF and LETM

Sagittal contrast-enhanced T1W (A and B), sagittal (C), axial (D), and axial (E) T2W MRIs of the spinal cord of an AQP4-IgG–positive NMOSD patient during attacks, showing leptomeningeal and intraparenchymal T1W contrast enhancement (A, B, and D). The spinal cord lesions were also demonstrated on T2W and STIR images (C and E). The patient had a subacute onset with atypical chest pain as the initial symptom, which after 7 days progressed to paraplegia and LETM on MRI. This patient was positive for AQP4-IgG in CSF. AQP4-IgG = aquaporin-4 immunoglobulin G; LETM = longitudinally extensive transverse myelitis; NMOSD = neuromyelitis optica spectrum disorder; STIR = short tau inversion recovery; T1W = T1 weighted; T2W = T2 weighted.