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Anti-myelin oligodendrocyte glycoprotein antibody-positive acute disseminated encephalomyelitis mimicking limbic encephalitis: A case report
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Anti-myelin oligodendrocyte glycoprotein antibody-positive acute disseminated encephalomyelitis mimicking limbic encephalitis: A case report Hirokazu Uchigami , Noritoshi Arai , Mariko Sekiguchi , Atsubumi Ogawa , Tsutomu Yasuda , Akiko Seto , Toshiyuki Takahashi , Sousuke Takeuchi PII: DOI: Reference:
S2211-0348(19)30489-4 https://doi.org/10.1016/j.msard.2019.101500 MSARD 101500
To appear in:
Multiple Sclerosis and Related Disorders
Received date: Revised date: Accepted date:
19 June 2019 13 August 2019 4 November 2019
Please cite this article as: Hirokazu Uchigami , Noritoshi Arai , Mariko Sekiguchi , Atsubumi Ogawa , Tsutomu Yasuda , Akiko Seto , Toshiyuki Takahashi , Sousuke Takeuchi , Anti-myelin oligodendrocyte glycoprotein antibody-positive acute disseminated encephalomyelitis mimicking limbic encephalitis: A case report, Multiple Sclerosis and Related Disorders (2019), doi: https://doi.org/10.1016/j.msard.2019.101500
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier B.V.
Highlights
A case with MOG-ab-positive ADEM involving bilateral medial temporal lesions.
Part of the clinical manifestations resembled characteristics of limbic encephalitis.
The case seemed to have more than a limbic encephalitis, resulting in the diagnosis.
The need to evaluate MOG-ab in encephalomyelitis involving bilateral limbic system.
Anti-myelin oligodendrocyte glycoprotein antibody-positive acute disseminated encephalomyelitis mimicking limbic encephalitis: A case report
Hirokazu Uchigami a,*, Noritoshi Arai a, Mariko Sekiguchi a, Atsubumi Ogawa a, Tsutomu Yasuda a, Akiko Seto a, Toshiyuki Takahashi b, and Sousuke Takeuchi a
a
Department of Neurology, Center Hospital of the National Center for Global Health and Medicine,
Tokyo, Japan
b
Department of Neurology, National Hospital Organization Yonezawa Hospital, Yamagata, Japan
*Corresponding author
Hirokazu Uchigami
Department of Neurology, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
Phone: +81-3-3202-7181
FAX: +81-3-3207-1038 E-mail: [email protected]
Abstract
Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-ab) have been detected in various disorders of the central nervous system including acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), optic neuritis, myelitis, and cortical encephalitis. We report an atypical case of MOG-ab-associated encephalomyelitis with part of the clinical manifestations resembling limbic encephalitis. Multifocal, hyperintense, bilateral lesions predominantly affecting the white matter on brain magnetic resonance imaging and marked response to steroid therapy were compatible with a MOG-ab-associated disease. This case illustrates that MOG-ab-associated disease should be considered in encephalomyelitis involving the bilateral limbic system.
Keywords: anti-myelin oligodendrocyte glycoprotein antibodies; acute disseminated encephalomyelitis; limbic encephalitis; bilateral limbic system
1. Introduction
Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-ab) are associated with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), optic neuritis, myelitis, and cortical encephalitis. (Ogawa et al., 2017). MOG-ab-positive ADEM is the predominant clinical association in children with MOG-ab (Jarius et al., 2018), whereas the clinical and neuroradiological characteristics of MOG-ab-positive ADEM in adults remain unclear. We present a 27-year-old man with MOG-ab-positive ADEM involving bilateral medial temporal lesions.
2. Case Presentation
A 27-year-old man developed acute fever, nausea, and vomiting for 5 days and presented to our hospital (day 1). He was alert, and physical examination was normal except for elevated body temperature (38.9°C). Neurological examination results revealed neck stiffness without focal neurological signs. Laboratory analysis showed elevated white blood count (8810/mm3 with 92% neutrophils) and C-reactive protein level (2.16 mg/dL). Non-contrast head computed tomography was normal. Cerebrospinal fluid (CSF) examination revealed elevated cell count (140/mm3; 84 monocytes/mm3) and protein (74 mg/dL), but bacterial culture was negative. Acyclovir was initiated for suspected viral meningitis, and he was admitted to the neurology department for evaluation and treatment.
On day 2, the patient developed memory disturbance and urinary retention and complained of numbness in the buttocks, legs, and feet. He was disoriented to date and place and repeated the same questions. He could not recall the three words he was asked to remember earlier. Neurological examination revealed weakness in limbs and sensory disturbance below T4, and he developed dysuria requiring catheterization. Deep tendon reflexes of lower extremities exhibited hyperreflexia, and plantar reflexes were extensor. He had paralysis in lower limbs (MMT grade 4+) but had no apparent visual impairment. On day 4, he developed dysesthesia with reduced pain sensation in the entire area below T5, and tactile sensation was reduced below T4. His Rivermead behavioral memory test score was 16 out of 24, which was in the moderately impaired range.
Brain magnetic resonance imaging (MRI) on day 4 showed abnormal, hyperintense areas in fluid attenuated inversion recovery (FLAIR) images of bilateral medial temporal lobes involving amygdala, hippocampus, and parahippocampal gyrus. MRI also revealed cortical and subcortical lesions in cingulate gyrus, insula, orbital gyrus, and right frontal operculum (Fig. 1A–D). T2-weighted MRI of the spinal cord showed a hyperintense lesion extending from C4 to conus on the sagittal view (Fig. 2A–D). The lesions were not enhanced by gadolinium. Hematological and blood chemistry did not reveal any apparent abnormalities, and he was negative for serum anti-neutrophil cytoplasmic antibody, anti-nuclear antibodies including anti-SS-A anti-SS-B, and anti-thyroid antibodies. CSF on day 4 was negative for oligoclonal bands, whereas myelin basic protein (MBP) level was elevated (5986.0 pg/mL; normal, <102 pg/mL). Polymerase chain reaction for herpes
simplex virus DNA was negative. The immunoglobulin (Ig) G index was 0.64. Visual evoked potential indicated that the P100 latencies and amplitudes were within normal limits. The critical flicker frequency was within the normal range. The clinical, laboratory, and neuroradiological findings led to the diagnosis of ADEM. The patient was positive for serum MOG-ab with the titer of 1:4,096 (cut-off 1:128) by our in-house live cell-based assay and negative for serum anti-aquaporin 4 antibody. Serum antibodies for autoimmune synaptic encephalitis, including anti-N-methyl-D-aspartate receptor, anti-leucine-rich glioma-inactivated 1, and contactin-associated protein 2, were absent.
The patient was started on steroid pulse therapy with intravenous methylprednisolone (1 g/day) for three consecutive days repeated every 4 weeks. The patient’s memory disturbance improved gradually with treatment. The urethral catheter was removed on day 14. On day 16, oral prednisolone (30 mg/day) was initiated and tapered at a rate of 5 mg over 1 week. Follow-up MRI on day 40 revealed no abnormal signals in the brain or spinal cord (Fig. 1E–F). On day 22, the CSF cell count was 14 /mm3 (13 monocytes/mm3) and the protein concentration was 39 mg/dL. On day 42, he was transferred to a rehabilitation hospital and was discharged after 1 month. At the last neurological examination at 5 months after admission, he had persistent minimal dysesthesia in distal areas of the lower limbs but no deterioration over 6 months. The clinical course, laboratory and MRI findings, and favorable response to steroid therapy were consistent with MOG-ab-positive ADEM.
3. Discussion
The entire clinical spectrum of the increasingly recognized MOG-ab-associated disorders remains unclear. The reported clinical phenotypes encompass ADEM, NMOSD, optic neuritis, myelitis, and cortical encephalitis. (Jarius et al., 2018; Ogawa et al., 2017).
Bilateral medial temporal lesions are atypical for MOG-ab-associated diseases. Subacute onset of memory deficits, CSF pleocytosis, and MRI hyperintense signal of both medial temporal lobes seem to be similar to the characteristics of autoimmune encephalitis. A report of atypical presentation of MOG-ab-associated disease in a patient with cortical and subcortical damage and bilateral involvement of mesial temporal lobes, thalamus, internal capsule, and pons (Mariotto et al., 2017) classified the case as encephalitis and not ADEM based on worse pleocytosis and absent spinal cord lesions; furthermore, the criteria for ADEM were established only for pediatric cases at the time. Conversely, the clinical features of our patient are compatible with ADEM based on the marked response to steroid therapy and MRI features fulfilling the clinical diagnostic criteria (Krupp et al., 2013). As reported previously, thalamic lesions are more frequent in MOG-ab-positive ADEM than MOG-ab-negative ADEM; however, whether the limbic system is involved in ADEM MOG-ab-positive ADEM is unclear (Cobo-Calvo et al., 2018). This case suggests that MOG-ab-related ADEM can atypically present with lesions involving the bilateral limbic system..
ADEM is the predominant clinical association in children with MOG-ab (Jarius et al., 2018). Comparison of the clinical and neuroradiological features of pediatric ADEM with and without MOG-ab concluded that MOG-ab-positive ADEM presented with large, bilateral, widespread lesions and longitudinal extensive transverse myelitis (LETM) (Baumann et al., 2015); they did not disclose the presence of lesions in the limbic system. Conversely, MOG-ab-positive ADEM is more frequent in children, and complete clinical and neuroradiological characterization of MOG-ab-positive ADEM in adults is lacking.Based on the radiological features, it is possible that encephalitis was partially responsible for the pathology in our case. Cobo-Calvo et al. reported that 8 of 42 MOG-ab-positive patients with abnormal brain MRI findings displayed cortical involvement on imaging and that some of them exhibited meningeal symptoms, retrograde amnesia, and seizures (Cobo-Calvo et al., 2018). They speculated that demyelination might not be the cause since no patient displayed elevated CSF MBP levels. Another study reported that 6 of 13 patients with MOG-ab-associated disease who had cortical involvement by brain MRI had frontal and/or parietal cortical lesions close to the cerebral flax (Wang et al., 2018). Our patient exhibited meningeal signs and abnormal cortical lesions on brain MRI, including anterior cingulate gyrus and straight gyrus at admission; therefore, encephalitis remains a possible etiology. Conversely, as reported previously, the radiological features of spinal cord MRI in MOG-ab-associated diseases are T2 hyperintense signals confined to gray matter (sagittal T2-hyperintense line combined with axial H sign) and absence of gadolinium enhancement (Dubey et al., 2018). In the current case, spinal MRI showed
LETM and the axial H sign. Although part of the clinical manifestations resembled autoimmune encephalitis, brain MRI lesions were not restricted to the medial temporal lobes and multifocal cortical and subcortical abnormalities and spinal cord lesions were also involved. The patient’s condition indicate more than limbic encephalitis, leading to the diagnosis of MOG-ab encephalomyelitis.
Sakai et al. reported the case of an atypical ADEM presentation with medial temporal cortical lesions mimicking acute bi (Sakai et al. 2011). Compared with our case, in this case, brain MRI findings were confined to the limbic systems on one side and spinal cord lesions were absent. However, antecedent infection, clinical manifestations such as memory disturbance, disorientation as to date and place, and severe urinary retention, and marked response to steroid therapy in this case are similar to those in our case. Although there was no mention of MOG-ab, it might contribute to the etiology of the case.
In conclusion, we described an atypical presentation of MOG-ab-associated disease with encephalomyelitis involving bilateral limbic system, which responded rapidly to steroid pulse therapy; the symptoms were associated with limbic encephalitis, illustrating the reported diversity in the clinical presentation of MOG-ab associated diseases. This case highlights the need to evaluate MOG-ab levels in encephalomyelitis involving bilateral limbic system considering that prompt treatment can lead to favorable outcomes.
Acknowledgements:
This study received no funds.
Conflict of Interest
None.
Role of Funding Source
None.
Declarations of interests: none
References
Baumann, M., Sahin, K., Lechner, C., Hennes, E.M., Schanda, K., Mader, S., Karenfort, M., Selch, C., Häusler, M., Eisenkölbl, A., Salandin, M., Gruber-Sedlmayr, U., Blaschek, A., Kraus, V., Leiz, S., Finsterwalder, J., Gotwald, T., Kuchukhidze, G., Berger, T., Reindl, M., Rostásy, K., 2015. Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J. Neurol. Neurosurg. Psychiatry. 86(3), 265–272.
Cobo-Calvo, A., Ruiz, A., Maillart, E., Audoin, B., Zephir, H., Bourre, B., Ciron, J., Collongues, N., Brassat, D., Cotton, F., Papeix, C., Durand-Dubief, F., Laplaud, D., Deschamps, R., Cohen, M., Biotti, D., Ayrignac, X., Tilikete, C., Thouvenot, E., Brochet, B., Dulau, C., Moreau, T., Tourbah, A., Lebranchu, P., Michel, L., Lebrun-Frenay, C., Montcuquet, A., Mathey, G., Debouverie, M., Pelletier, J., Labauge, P., Derache, N., Coustans, M., Rollot, F., De Seze, J., Vukusic, S., Marignier, R. OFSEP and NOMADMUS Study Group, 2018. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study. Neurology. 90(21), e1858–e1869.
Dubey, D., Pittock, S.J., Krecke, K.N., Morris, P.P., Sechi, E., Zalewski, N.L., Weinshenker, B.G., Shosha, E., Lucchinetti, C.F., Fryer, J.P., Lopez-Chiriboga, A.S., Chen, J.C., Jitprapaikulsan, J., McKeon, A., Gadoth, A., Keegan, B.M., Tillema, J.M., Naddaf, E., Patterson, M.C., Messacar, K., Tyler, K.L., Flanagan, E.P, 2018. Clinical, radiologic, and prognostic features of myelitis associated with myelin oligodendrocyte glycoprotein autoantibody. JAMA Neurol. 76(3), 301–309.
Jarius, S., Paul, F., Aktas, O., Asgari, N., Dale, R.C., de Seze, J., Franciotta, D., Fujihara, K., Jacob, A., Kim, H.J., Kleiter, I., Kümpfel, T., Levy, M., Palace, J., Ruprecht, K., Saiz, A., Trebst, C., Weinshenker, B.G., Wildemann, B., 2018. MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation. 15(1), 134.
Mariotto, S., Monaco, S., Peschl, P., Coledan, I., Mazzi, R., Höftberger, R., Reindl, M., Ferrari, S., 2017. MOG antibody seropositivity in a patient with encephalitis: beyond the classical syndrome. BMC Neurol. 17(1), 190.
Ogawa, R., Nakashima, I., Takahashi, T., Kaneko, K., Akaishi, T., Takai, Y., Sato, D.K., Nishiyama, S., Misu. T., Kuroda, H., Aoki, M., Fujihara, K., 2017. MOG antibody-positive, benign, unilateral, cerebral cortical encephalitis with epilepsy. Neurol. Neuroimmunol. Neuroinflamm. 4(2), e322.
Wang, L., ZhangBao, J., Zhou, L., Zhang, Y., Li, H., Li, Y., Huang, Y., Wang, M., Lu, C., Lu, J., Zhao, C., Quan, C., 2019. Encephalitis is an important clinical component of myelin oligodendrocyte glycoprotein antibodyassociated demyelination: a single-center cohort study in Shanghai, China. Eur. J. Neurol. 26(1), 168–174.
Sakai K., Yoshita M., Samuraki M., Yamada M., 2011. Acute disseminated encephalomyelitis with medial temporal lesions mimicking acute limbic encephalitis. Clin. Neurol. Neurosurg. 113(1):72-74.
Figure legends
Figure 1. Brain magnetic resonance images (MRI) at onset (A–D) and after treatment (E–F). (A–D) Fluid attenuated inversion recovery (FLAIR) axial images show hyperintense areas in bilateral medial temporal lobes and subcortical and cortical lesions in cingulate gyrus, insula, orbital gyrus, and right frontal operculum. (E–F) After treatment with intravenous methylprednisolone, FLAIR images demonstrate improvement of cortical and subcortical lesions.
Figure 2. Spine MRI at onset. Spine MRI on day 5. (A–D) Spinal cord T2-weighted MRI showing hyperintense lesions extending from C4 to conus, mainly including gray matter on sagittal and axial views (C, C6 level; D, T4 level).
Anti-myelin oligodendrocyte glycoprotein antibody-positive acute disseminated encephalomyelitis mimicking limbic encephalitis: A case report Hirokazu Uchigami , Noritoshi Arai , Mariko Sekiguchi , Atsubumi Ogawa , Tsutomu Yasuda , Akiko Seto , Toshiyuki Takahashi , Sousuke Takeuchi PII: DOI: Reference:
S2211-0348(19)30489-4 https://doi.org/10.1016/j.msard.2019.101500 MSARD 101500
To appear in:
Multiple Sclerosis and Related Disorders
Received date: Revised date: Accepted date:
19 June 2019 13 August 2019 4 November 2019
Please cite this article as: Hirokazu Uchigami , Noritoshi Arai , Mariko Sekiguchi , Atsubumi Ogawa , Tsutomu Yasuda , Akiko Seto , Toshiyuki Takahashi , Sousuke Takeuchi , Anti-myelin oligodendrocyte glycoprotein antibody-positive acute disseminated encephalomyelitis mimicking limbic encephalitis: A case report, Multiple Sclerosis and Related Disorders (2019), doi: https://doi.org/10.1016/j.msard.2019.101500
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier B.V.
Highlights
A case with MOG-ab-positive ADEM involving bilateral medial temporal lesions.
Part of the clinical manifestations resembled characteristics of limbic encephalitis.
The case seemed to have more than a limbic encephalitis, resulting in the diagnosis.
The need to evaluate MOG-ab in encephalomyelitis involving bilateral limbic system.
Anti-myelin oligodendrocyte glycoprotein antibody-positive acute disseminated encephalomyelitis mimicking limbic encephalitis: A case report
Hirokazu Uchigami a,*, Noritoshi Arai a, Mariko Sekiguchi a, Atsubumi Ogawa a, Tsutomu Yasuda a, Akiko Seto a, Toshiyuki Takahashi b, and Sousuke Takeuchi a
a
Department of Neurology, Center Hospital of the National Center for Global Health and Medicine,
Tokyo, Japan
b
Department of Neurology, National Hospital Organization Yonezawa Hospital, Yamagata, Japan
*Corresponding author
Hirokazu Uchigami
Department of Neurology, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
Phone: +81-3-3202-7181
FAX: +81-3-3207-1038 E-mail: [email protected]
Abstract
Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-ab) have been detected in various disorders of the central nervous system including acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), optic neuritis, myelitis, and cortical encephalitis. We report an atypical case of MOG-ab-associated encephalomyelitis with part of the clinical manifestations resembling limbic encephalitis. Multifocal, hyperintense, bilateral lesions predominantly affecting the white matter on brain magnetic resonance imaging and marked response to steroid therapy were compatible with a MOG-ab-associated disease. This case illustrates that MOG-ab-associated disease should be considered in encephalomyelitis involving the bilateral limbic system.
Keywords: anti-myelin oligodendrocyte glycoprotein antibodies; acute disseminated encephalomyelitis; limbic encephalitis; bilateral limbic system
1. Introduction
Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-ab) are associated with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), optic neuritis, myelitis, and cortical encephalitis. (Ogawa et al., 2017). MOG-ab-positive ADEM is the predominant clinical association in children with MOG-ab (Jarius et al., 2018), whereas the clinical and neuroradiological characteristics of MOG-ab-positive ADEM in adults remain unclear. We present a 27-year-old man with MOG-ab-positive ADEM involving bilateral medial temporal lesions.
2. Case Presentation
A 27-year-old man developed acute fever, nausea, and vomiting for 5 days and presented to our hospital (day 1). He was alert, and physical examination was normal except for elevated body temperature (38.9°C). Neurological examination results revealed neck stiffness without focal neurological signs. Laboratory analysis showed elevated white blood count (8810/mm3 with 92% neutrophils) and C-reactive protein level (2.16 mg/dL). Non-contrast head computed tomography was normal. Cerebrospinal fluid (CSF) examination revealed elevated cell count (140/mm3; 84 monocytes/mm3) and protein (74 mg/dL), but bacterial culture was negative. Acyclovir was initiated for suspected viral meningitis, and he was admitted to the neurology department for evaluation and treatment.
On day 2, the patient developed memory disturbance and urinary retention and complained of numbness in the buttocks, legs, and feet. He was disoriented to date and place and repeated the same questions. He could not recall the three words he was asked to remember earlier. Neurological examination revealed weakness in limbs and sensory disturbance below T4, and he developed dysuria requiring catheterization. Deep tendon reflexes of lower extremities exhibited hyperreflexia, and plantar reflexes were extensor. He had paralysis in lower limbs (MMT grade 4+) but had no apparent visual impairment. On day 4, he developed dysesthesia with reduced pain sensation in the entire area below T5, and tactile sensation was reduced below T4. His Rivermead behavioral memory test score was 16 out of 24, which was in the moderately impaired range.
Brain magnetic resonance imaging (MRI) on day 4 showed abnormal, hyperintense areas in fluid attenuated inversion recovery (FLAIR) images of bilateral medial temporal lobes involving amygdala, hippocampus, and parahippocampal gyrus. MRI also revealed cortical and subcortical lesions in cingulate gyrus, insula, orbital gyrus, and right frontal operculum (Fig. 1A–D). T2-weighted MRI of the spinal cord showed a hyperintense lesion extending from C4 to conus on the sagittal view (Fig. 2A–D). The lesions were not enhanced by gadolinium. Hematological and blood chemistry did not reveal any apparent abnormalities, and he was negative for serum anti-neutrophil cytoplasmic antibody, anti-nuclear antibodies including anti-SS-A anti-SS-B, and anti-thyroid antibodies. CSF on day 4 was negative for oligoclonal bands, whereas myelin basic protein (MBP) level was elevated (5986.0 pg/mL; normal, <102 pg/mL). Polymerase chain reaction for herpes
simplex virus DNA was negative. The immunoglobulin (Ig) G index was 0.64. Visual evoked potential indicated that the P100 latencies and amplitudes were within normal limits. The critical flicker frequency was within the normal range. The clinical, laboratory, and neuroradiological findings led to the diagnosis of ADEM. The patient was positive for serum MOG-ab with the titer of 1:4,096 (cut-off 1:128) by our in-house live cell-based assay and negative for serum anti-aquaporin 4 antibody. Serum antibodies for autoimmune synaptic encephalitis, including anti-N-methyl-D-aspartate receptor, anti-leucine-rich glioma-inactivated 1, and contactin-associated protein 2, were absent.
The patient was started on steroid pulse therapy with intravenous methylprednisolone (1 g/day) for three consecutive days repeated every 4 weeks. The patient’s memory disturbance improved gradually with treatment. The urethral catheter was removed on day 14. On day 16, oral prednisolone (30 mg/day) was initiated and tapered at a rate of 5 mg over 1 week. Follow-up MRI on day 40 revealed no abnormal signals in the brain or spinal cord (Fig. 1E–F). On day 22, the CSF cell count was 14 /mm3 (13 monocytes/mm3) and the protein concentration was 39 mg/dL. On day 42, he was transferred to a rehabilitation hospital and was discharged after 1 month. At the last neurological examination at 5 months after admission, he had persistent minimal dysesthesia in distal areas of the lower limbs but no deterioration over 6 months. The clinical course, laboratory and MRI findings, and favorable response to steroid therapy were consistent with MOG-ab-positive ADEM.
3. Discussion
The entire clinical spectrum of the increasingly recognized MOG-ab-associated disorders remains unclear. The reported clinical phenotypes encompass ADEM, NMOSD, optic neuritis, myelitis, and cortical encephalitis. (Jarius et al., 2018; Ogawa et al., 2017).
Bilateral medial temporal lesions are atypical for MOG-ab-associated diseases. Subacute onset of memory deficits, CSF pleocytosis, and MRI hyperintense signal of both medial temporal lobes seem to be similar to the characteristics of autoimmune encephalitis. A report of atypical presentation of MOG-ab-associated disease in a patient with cortical and subcortical damage and bilateral involvement of mesial temporal lobes, thalamus, internal capsule, and pons (Mariotto et al., 2017) classified the case as encephalitis and not ADEM based on worse pleocytosis and absent spinal cord lesions; furthermore, the criteria for ADEM were established only for pediatric cases at the time. Conversely, the clinical features of our patient are compatible with ADEM based on the marked response to steroid therapy and MRI features fulfilling the clinical diagnostic criteria (Krupp et al., 2013). As reported previously, thalamic lesions are more frequent in MOG-ab-positive ADEM than MOG-ab-negative ADEM; however, whether the limbic system is involved in ADEM MOG-ab-positive ADEM is unclear (Cobo-Calvo et al., 2018). This case suggests that MOG-ab-related ADEM can atypically present with lesions involving the bilateral limbic system..
ADEM is the predominant clinical association in children with MOG-ab (Jarius et al., 2018). Comparison of the clinical and neuroradiological features of pediatric ADEM with and without MOG-ab concluded that MOG-ab-positive ADEM presented with large, bilateral, widespread lesions and longitudinal extensive transverse myelitis (LETM) (Baumann et al., 2015); they did not disclose the presence of lesions in the limbic system. Conversely, MOG-ab-positive ADEM is more frequent in children, and complete clinical and neuroradiological characterization of MOG-ab-positive ADEM in adults is lacking.Based on the radiological features, it is possible that encephalitis was partially responsible for the pathology in our case. Cobo-Calvo et al. reported that 8 of 42 MOG-ab-positive patients with abnormal brain MRI findings displayed cortical involvement on imaging and that some of them exhibited meningeal symptoms, retrograde amnesia, and seizures (Cobo-Calvo et al., 2018). They speculated that demyelination might not be the cause since no patient displayed elevated CSF MBP levels. Another study reported that 6 of 13 patients with MOG-ab-associated disease who had cortical involvement by brain MRI had frontal and/or parietal cortical lesions close to the cerebral flax (Wang et al., 2018). Our patient exhibited meningeal signs and abnormal cortical lesions on brain MRI, including anterior cingulate gyrus and straight gyrus at admission; therefore, encephalitis remains a possible etiology. Conversely, as reported previously, the radiological features of spinal cord MRI in MOG-ab-associated diseases are T2 hyperintense signals confined to gray matter (sagittal T2-hyperintense line combined with axial H sign) and absence of gadolinium enhancement (Dubey et al., 2018). In the current case, spinal MRI showed
LETM and the axial H sign. Although part of the clinical manifestations resembled autoimmune encephalitis, brain MRI lesions were not restricted to the medial temporal lobes and multifocal cortical and subcortical abnormalities and spinal cord lesions were also involved. The patient’s condition indicate more than limbic encephalitis, leading to the diagnosis of MOG-ab encephalomyelitis.
Sakai et al. reported the case of an atypical ADEM presentation with medial temporal cortical lesions mimicking acute bi (Sakai et al. 2011). Compared with our case, in this case, brain MRI findings were confined to the limbic systems on one side and spinal cord lesions were absent. However, antecedent infection, clinical manifestations such as memory disturbance, disorientation as to date and place, and severe urinary retention, and marked response to steroid therapy in this case are similar to those in our case. Although there was no mention of MOG-ab, it might contribute to the etiology of the case.
In conclusion, we described an atypical presentation of MOG-ab-associated disease with encephalomyelitis involving bilateral limbic system, which responded rapidly to steroid pulse therapy; the symptoms were associated with limbic encephalitis, illustrating the reported diversity in the clinical presentation of MOG-ab associated diseases. This case highlights the need to evaluate MOG-ab levels in encephalomyelitis involving bilateral limbic system considering that prompt treatment can lead to favorable outcomes.
Acknowledgements:
This study received no funds.
Conflict of Interest
None.
Role of Funding Source
None.
Declarations of interests: none
References
Baumann, M., Sahin, K., Lechner, C., Hennes, E.M., Schanda, K., Mader, S., Karenfort, M., Selch, C., Häusler, M., Eisenkölbl, A., Salandin, M., Gruber-Sedlmayr, U., Blaschek, A., Kraus, V., Leiz, S., Finsterwalder, J., Gotwald, T., Kuchukhidze, G., Berger, T., Reindl, M., Rostásy, K., 2015. Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J. Neurol. Neurosurg. Psychiatry. 86(3), 265–272.
Cobo-Calvo, A., Ruiz, A., Maillart, E., Audoin, B., Zephir, H., Bourre, B., Ciron, J., Collongues, N., Brassat, D., Cotton, F., Papeix, C., Durand-Dubief, F., Laplaud, D., Deschamps, R., Cohen, M., Biotti, D., Ayrignac, X., Tilikete, C., Thouvenot, E., Brochet, B., Dulau, C., Moreau, T., Tourbah, A., Lebranchu, P., Michel, L., Lebrun-Frenay, C., Montcuquet, A., Mathey, G., Debouverie, M., Pelletier, J., Labauge, P., Derache, N., Coustans, M., Rollot, F., De Seze, J., Vukusic, S., Marignier, R. OFSEP and NOMADMUS Study Group, 2018. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study. Neurology. 90(21), e1858–e1869.
Dubey, D., Pittock, S.J., Krecke, K.N., Morris, P.P., Sechi, E., Zalewski, N.L., Weinshenker, B.G., Shosha, E., Lucchinetti, C.F., Fryer, J.P., Lopez-Chiriboga, A.S., Chen, J.C., Jitprapaikulsan, J., McKeon, A., Gadoth, A., Keegan, B.M., Tillema, J.M., Naddaf, E., Patterson, M.C., Messacar, K., Tyler, K.L., Flanagan, E.P, 2018. Clinical, radiologic, and prognostic features of myelitis associated with myelin oligodendrocyte glycoprotein autoantibody. JAMA Neurol. 76(3), 301–309.
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Figure legends
Figure 1. Brain magnetic resonance images (MRI) at onset (A–D) and after treatment (E–F). (A–D) Fluid attenuated inversion recovery (FLAIR) axial images show hyperintense areas in bilateral medial temporal lobes and subcortical and cortical lesions in cingulate gyrus, insula, orbital gyrus, and right frontal operculum. (E–F) After treatment with intravenous methylprednisolone, FLAIR images demonstrate improvement of cortical and subcortical lesions.
Figure 2. Spine MRI at onset. Spine MRI on day 5. (A–D) Spinal cord T2-weighted MRI showing hyperintense lesions extending from C4 to conus, mainly including gray matter on sagittal and axial views (C, C6 level; D, T4 level).