Dear Editor,
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) produces various manifestations, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and brainstem demyelination.1 However, brain magnetic resonance imaging (MRI) may also demonstrate leptomeningeal enhancement (LME) involving the brain cortex and other sites.1 We present a case of MOGAD that presented not only with LME but also with a rare imaging feature that involved the caudate nucleus (CN). Furthermore, we systematically reviewed articles that reported similar phenotypes, and compared our case with the results of the literature review.
We present a 33 year-old female with a history of traveling to Finland and Las Vegas 2 weeks before the onset of the symptoms of fever (up to 38.5℃), headache, and nausea. She and her family denied any psychiatric or cognitive symptoms. A neurological examination revealed no focal neurological deficit except for neck stiffness with a positive Kernig’s sign. To rule out meningitis, she underwent spinal tapping for cerebrospinal fluid (CSF) analysis that revealed pleocytosis (white blood cell [WBC] count=250/µL, 90% lymphocytes), elevated proteins (127.6 mg/dL), slightly decreased glucose levels (54 mg/dL; 120 mg/dL in serum), and increased immunoglobulin G index (0.71). Oligoclonal bands were absent. The cytology was negative for malignant cells. Brain MRI indicated LME that predominated in the left cerebral cortex and a T2-weighted hyperintense lesion with gadolinium enhancement that involved the head of the CN and the putamen (Supplementary Fig. 1A and B in the online-only Data Supplement). Regional slowing of the left frontotemporal area was confirmed on electroencephalography. Although intravenous (IV) acyclovir was administered before the CSF analysis, various CSF infection tests were subsequently found to be negative, including metagenomics for bacterial 16S and fungal internal transcribed spacer, cultures for bacteria, fungi, and tuberculosis (Tb), and polymerase chain reactions (PCRs) for several viruses and Tb. Nonetheless, flavivirus infections such as tick-borne encephalitis (TBE) could not be ruled out. She was therefore treated using IV immunoglobulin (IVIg, 2 g/kg for 5 days) for the two scenarios of autoimmunity and infection.
MOG antibody was subsequently confirmed as positive using fluorescence-activating cell sorting (ratio of positive cell=0.744 [positive >0.254], mean fluorescence intensity of fluorescein isothiocyanate channel=5.63 [positive >3.65]). She was negative for other autoimmune antibodies, including anti-aquaporin-4 antibody (Supplementary Materials in the online-only Data Supplement). Ophthalmological tests were performed using fundoscopy and optical coherence tomography, which indicated that both optic nerves were normal. The findings of whole-spine MRI were also normal. PCR for the TBE virus and reverse transcriptase PCR for the Japanese encephalitis virus (JEV) were negative.
Agraphia developed in this patient despite receiving IVIg treatment. Under the assumption of MOGAD, we considered IV steroids because of concern about rapid deterioration. However, steroid administration can mask malignancies such as lymphoma, which could not be easily precluded by only one cytology assessment with a small sample volume. Rituximab and subsequently tocilizumab were therefore administered considering the delayed onset of response to rituximab. In the follow-up CSF analysis with an abundant sample volume of the cytology, pleocytosis and protein elevation improved but persisted (WBC=40/µL, 95% lymphocytes, proteins=89 mg/dL), and the cytology was negative for malignant cells. Her fever, headache, and agraphia improved after rituximab and tocilizumab therapy. Furthermore, the CN lesion and LME were found to have improved in the follow-up brain MRI performed 2 weeks after the initial MRI (Supplementary Fig. 1C and D in the online-only Data Supplement).
The literature review identified 34 patients with MOGAD and LME in 25 articles (The detailed data arrangement process is illustrated in the Supplementary Materials in the online-only Data Supplement). With our case added to the selected patient list, we investigated demographics, prevalence of clinical and laboratory manifestations, and the anatomical distribution of MRI lesions among these patients.
The sex ratio was 0.94 males per 1 female. The mean age was 24.45 years, encompassing both children and adult patients. Most patients reported fever, headache, and seizure as the presenting symptoms. Antecedent or subsequent optic neuritis and myelitis were present in 42.9% and 25.7% of patients, respectively. The CSF profile indicated pleocytosis in 96.3%, and the WBC was 115.38±124.91/µL (mean±standard deviation). Protein levels were elevate in 66.7% (73.24±35.57 mg/dL). Oligoclonal bands were present in only 14.3%. Cortical/subcortical lesions were most common (85.7%) on brain MRI, but infiltration of the basal ganglia was also observed in 20.0%. Among them, five patients (14.3%), including ours, had LME with CN lesions (Table 1).
Table 1. Demographics, clinical manifestations, and radiological findings of MOGAD patients with leptomeningeal enhancement in literature review and our case (n=35).
| Available | Unavailable | ||||
|---|---|---|---|---|---|
| Presence | Absence | ||||
| Sex | |||||
| Males | 48.6 (17/35) | NA | 0.0 (0/35) | ||
| Females | 51.4 (18/35) | NA | 0.0 (0/35) | ||
| Age, years | 94.3 (33/35) | NA | 5.7 (2/35) | ||
| 24.45±12.12 (2–55) | NA | NA | |||
| Precedent infection or vaccination | 14.3 (5/35) | 62.9 (22/35) | 22.9 (8/35) | ||
| Detail | Covid-19 (2), vaginal herpes (1), ChAdOx1 vaccine (1), unknown (1) | NA | NA | ||
| History of traveling | 5.7 (2/35) | 71.4 (25/35) | 22.9 (8/35) | ||
| Presence of tumor | 5.7 (2/35) | 88.6 (31/35) | 5.7 (2/35) | ||
| Detail | Ovarian teratoma (1), ovarian borderline tumor (1) | NA | NA | ||
| Symptoms | |||||
| Fever | 60.0 (21/35) | 20.0 (7/35) | 20.0 (7/35) | ||
| Headache | 71.4 (25/35) | 8.6 (3/35) | 20.0 (7/35) | ||
| Seizure | 54.3 (19/35) | 42.9 (15/35) | 2.9 (1/35) | ||
| Demyelination | |||||
| Optic neuritis | 42.9 (15/35) | 57.1 (20/35) | 0.0 (0/35) | ||
| Myelitis | 25.7 (9/35) | 74.3 (26/35) | 0.0 (0/35) | ||
| CSF study | 77.1 (27/35) | 0.0 (0/35) | 22.9 (8/35) | ||
| Pleocytosis, among the presence of CSF study | Presence 96.3 (26/27) | NA | NA | ||
| Absence 3.7 (1/27) | |||||
| Unavailable 0.0 (0/27) | |||||
| WBC count among the presence of CSF study | 115.38±124.91 | NA | NA | ||
| Lympho-dominant pleocytosis | Presence 53.8 (14/26) | NA | NA | ||
| Absence 11.5 (3/26) | |||||
| Unavailable 34.6 (9/26) | |||||
| Elevated protein | Presence 66.7 (18/27) | NA | NA | ||
| Absence 25.9 (7/27) | |||||
| Unavailable 7.4 (2/27) | |||||
| Protein level (available only) | 73.24±35.57 | NA | NA | ||
| Decreased glucose | Presence 14.8 (4/27) | NA | NA | ||
| Absence 25.9 (7/27) | |||||
| Unavailable 59.3 (16/27) | |||||
| Glucose level (available only) | 51.85±7.86 | NA | NA | ||
| Oligoclonal band | 14.3 (5/35) | 54.3 (19/35) | 31.4 (11/35) | ||
| MRI | 100.0 (35/35) | 0.0 (0/35) | 0.0 (0/35) | ||
| Cortical/subcortical | 85.7 (30/35) | 14.3 (5/35) | 0.0 (0/35) | ||
| Frontal | 45.7 (16/35) | 54.3 (19/35) | 0.0 (0/35) | ||
| Insular | 17.1 (6/35) | 82.9 (29/35) | 0.0 (0/35) | ||
| Cingulate | 8.6 (3/35) | 91.4 (32/35) | 0.0 (0/35) | ||
| Parietal | 40.0 (14/35) | 60.0 (21/35) | 0.0 (0/35) | ||
| Temporal | 42.9 (15/35) | 57.1 (20/35) | 0.0 (0/35) | ||
| Occipital | 17.1 (6/35) | 82.9 (29/35) | 0.0 (0/35) | ||
| Midbrain | 11.4 (4/35) | 88.6 (31/35) | 0.0 (0/35) | ||
| Pons | 17.1 (6/35) | 82.9 (29/35) | 0.0 (0/35) | ||
| Medulla | 8.6 (3/35) | 91.4 (32/35) | 0.0 (0/35) | ||
| Cerebellum | 14.3 (5/35) | 85.7 (30/35) | 0.0 (0/35) | ||
| Corpus callosum | 14.3 (5/35) | 85.7 (30/35) | 0.0 (0/35) | ||
| PVWM | 8.6 (3/35) | 91.4 (32/35) | 0.0 (0/35) | ||
| Thalamus | 17.1 (6/35) | 82.9 (29/35) | 0.0 (0/35) | ||
| Basal ganglia | 20.0 (7/35) | 80.0 (28/35) | 0.0 (0/35) | ||
| Caudate | 14.3 (5/35) | 85.7 (30/35) | 0.0 (0/35) | ||
| Globus pallidus | 0.0 (0/35) | 100.0 (35/35) | 0.0 (0/35) | ||
| Putamen | 11.4 (4/35) | 88.6 (31/35) | 0.0 (0/35) | ||
| Other autoantibodies | 31.4 (11/35) | 68.6 (24/35) | 0.0 (0/35) | ||
| Detail | NMDAR (5), GFAP (2), NMDAR+GFAP (1), GAD (1), TPO (1), ANA (1) | NA | NA | ||
| Initial therapy | |||||
| Antiviral agents* | 31.4 (11/35) | 20.0 (2/35) | 48.6 (22/35) | ||
| Antibiotics* | 31.4 (11/35) | 20.0 (2/35) | 48.6 (22/35) | ||
Data are % (n/n) or mean±SD values.
*Nine patients were treated with both antiviral and antibiotics.
CSF, cerebrospinal fluid; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease; MRI, magnetic resonance imaging; NA, not applicable; PVWM, periventricular white matter; WBC, white blood cell.
Multiple differential diagnoses should be considered in cases of LME with a CN lesion. Among infectious meningoencephalitis, TBE virus, West Nile virus, and JEV can be suspected.2 Finck et al.2 recently suggested that the Borna disease virus initially prefers CN invasion. Various autoimmune diseases may also present with a CN lesion.3 MRI findings of Rasmussen encephalitis can present with involvement of the unilateral CN head and cortex with or without atrophy, which was similar to the condition of our patient.
While LME may be an important feature of MOGAD, previous cohort studies have paid little attention to LME.4,5,6,7,8 A systematic analysis by Ineichen et al.9 of LME in various neurological disorders indicated that the prevalence of LME was lower in neuromyelitis optica spectrum disorder, and LME was associated with some manifestations of multiple sclerosis. Still, LME in MOGAD has not been demonstrated accurately, which calls for further research in this area.
In conclusion, MOGAD should be considered when in presentations of LME with CN lesions.
Footnotes
Ethics Statement: This study followed the tenets of the Declaration of Helsinki. Written informed consent was obtained from the patient.
- Conceptualization: Kon Chu.
- Data curation: Seondeuk Kim, Seoyeon Kim.
- Formal analysis: Seondeuk Kim, Seoyeon Kim.
- Supervision: Yoonhyuk Jang, Kon Chu.
- Writing—original draft: Seondeuk Kim.
- Writing—review & editing: Yoonhyuk Jang, Kon Chu.
Conflicts of Interest: The authors have no potential conflicts of interest to disclose.
Funding Statement: None
Availability of Data and Material
The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.
Supplementary Materials
The online-only Data Supplement is available with this article at https://doi.org/10.3988/jcn.2022.0307.
Initial and follow-up brain MRI images of the patient. A: The red arrow indicates a T2 FLAIR hyperintense lesion in the left head of the caudate nucleus and putamen. B: The red arrows indicate left dominant leptomeningeal enhancement in black-blood contrast-enhanced T1 weighted image. C: The follow-up brain MRI 2 months later after the immunotherapy. The red arrow indicates the improved T2 FLAIR hypertense lesion. D: The follow-up MRI 2 weeks later after the immunotherapy. The red arrows indicate the improvement of leptomeningeal enhancement. FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging.
References
- 1.Marignier R, Hacohen Y, Cobo-Calvo A, Pröbstel AK, Aktas O, Alexopoulos H, et al. Myelin-oligodendrocyte glycoprotein antibody-associated disease. Lancet Neurol. 2021;20:762–772. doi: 10.1016/S1474-4422(21)00218-0. [DOI] [PubMed] [Google Scholar]
- 2.Finck T, Liesche-Starnecker F, Probst M, Bette S, Ruf V, Wendl C, et al. Bornavirus encephalitis shows a characteristic magnetic resonance phenotype in humans. Ann Neurol. 2020;88:723–735. doi: 10.1002/ana.25873. [DOI] [PubMed] [Google Scholar]
- 3.Bekiesinska-Figatowska M, Mierzewska H, Jurkiewicz E. Basal ganglia lesions in children and adults. Eur J Radiol. 2013;82:837–849. doi: 10.1016/j.ejrad.2012.12.006. [DOI] [PubMed] [Google Scholar]
- 4.Gadde JA, Wolf DS, Keller S, Gombolay GY. Rate of leptomeningeal enhancement in pediatric myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis. J Child Neurol. 2021;36:1042–1046. doi: 10.1177/08830738211025867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Salama S, Khan M, Shanechi A, Levy M, Izbudak I. MRI differences between MOG antibody disease and AQP4 NMOSD. Mult Scler. 2020;26:1854–1865. doi: 10.1177/1352458519893093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Li H, Yang L, Wu Z, Zhou L, Bao Y, Geng D, et al. Brain MRI features of Chinese Han patients with MOG-antibody disease. Mult Scler Relat Disord. 2020;43:102167. doi: 10.1016/j.msard.2020.102167. [DOI] [PubMed] [Google Scholar]
- 7.Hou C, Wu W, Tian Y, Zhang Y, Zhu H, Zeng Y, et al. Clinical analysis of anti-NMDAR encephalitis combined with MOG antibody in children. Mult Scler Relat Disord. 2020;42:102018. doi: 10.1016/j.msard.2020.102018. [DOI] [PubMed] [Google Scholar]
- 8.Cobo-Calvo A, Ruiz A, Maillart E, Audoin B, Zephir H, Bourre B, et al. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology. 2018;90:e1858–e1869. doi: 10.1212/WNL.0000000000005560. [DOI] [PubMed] [Google Scholar]
- 9.Ineichen BV, Tsagkas C, Absinta M, Reich DS. Leptomeningeal enhancement in multiple sclerosis and other neurological diseases: a systematic review and meta-analysis. Neuroimage Clin. 2022;33:102939. doi: 10.1016/j.nicl.2022.102939. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Initial and follow-up brain MRI images of the patient. A: The red arrow indicates a T2 FLAIR hyperintense lesion in the left head of the caudate nucleus and putamen. B: The red arrows indicate left dominant leptomeningeal enhancement in black-blood contrast-enhanced T1 weighted image. C: The follow-up brain MRI 2 months later after the immunotherapy. The red arrow indicates the improved T2 FLAIR hypertense lesion. D: The follow-up MRI 2 weeks later after the immunotherapy. The red arrows indicate the improvement of leptomeningeal enhancement. FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging.
Data Availability Statement
The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.