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Encephalitis seldom causes paraparesis as the initial symptom. Here, we report a case of steroid-responsive bilateral frontal cortical encephalitis involving leg motor areas in a patient who presented with paraparesis on admission. Interestingly, the initial paraparesis evolved into an acute disseminated encephalomyelitis (ADEM)-like illness and optic neuritis, and the patient was found to be positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies.
A 46-year-old man experienced transient dizziness in early September 2008. Brain MRI retrospectively showed a slight fluid attenuation inversion recovery (FLAIR) high-intensity lesion involving the left frontal cortex (figure 1). One week later, the patient experienced a focal motor seizure in the right leg that subsequently generalised. Thereafter, he gradually developed headache and paraparesis over the course of a week. On admission, he presented with paraparesis without other neurological deficits, but the spinal MRI was normal. An electroencephalogram revealed that there were no epileptic discharges. A cerebrospinal fluid (CSF) examination revealed elevated leucocytes (56 /µL; 93% mononuclear cells, 3% polymorphonuclear leucocytes) and normal protein (36 mg/dL) and glucose (59 mg/dL) levels. The myelin basic protein (MBP) and glial fibrillary acidic protein levels in the CSF were not elevated. Cell-based assays for anti-N-methyl-D-aspartate receptor (NMDAR) antibodies, anti-voltage-gated potassium channel (VGKC) antibodies, anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antibodies and anti-γ-aminobutyric acid-B receptor (GABA(B)R) antibodies in the CSF were negative. Blood and CSF examinations for infectious central nervous system (CNS) CNS diseases, collagen diseases, vasculitis, Behçet disease, sarcoidosis, lymphoma, paraneoplastic syndrome, vitamin B deficiency and Hashimoto encephalopathy were unremarkable.
After admission, paraparesis progressed gradually, and the patient became completely paraplegic with spasticity 12 days after admission. Furthermore, fever, memory decline and lethargy appeared. iT2-weighted and FLAIR MRI of the brain showed hyperintensities involving the corpus callosum, bilateral cingulate gyri and the medial aspect of the bilateral frontal lobes with contrast enhancement (figure 1B–F). We suspected a certain type of encephalitis, therefore, high-dose intravenous methylprednisolone (1 g for 3 days) and aciclovir (1500 mg/day) were started. His symptoms then improved, and oral prednisolone (PSL) (60 mg/day) was administered beginning in early October 2008. At that time, a CSF examination indicated positive oligoclonal IgG bands, which later became negative in mid-October 2008. CSF-MBP was not elevated at re-evaluation in early October 2008.
Owing to diagnostic uncertainty, a brain biopsy was performed at the right cingulate gyrus in early November 2008. The pathological examination revealed relatively mild tissue damage without demyelinating plaques, neuronal or axonal loss or astrocytic destruction despite the inflammatory and oedematous changes with T-cell and B-cell infiltration. No neoplastic cells were observed (figure 1M–S). Symptomatic improvement was evident, so PSL was tapered to 20 mg/day.
In late November 2008, although the original FLAIR hyperintense area became smaller, new asymptomatic FLAIR hyperintense lesions appeared around the third ventricle and cerebral aqueduct, as well as in the bilateral thalamus and the right nucleus basalis. However, these lesions later spontaneously regressed (figure 1H–K). PSL was tapered to 7 mg/day. In March 2009, the patient could walk without assistance and was discharged. At this time, the original FLAIR high-intensity area had also became markedly smaller.
In late July 2010, PSL was further tapered from 5 mg/day to 4 mg/day. After 1 month, the patient relapsed with right optic neuritis (figure 1L). He had 20/200 vision in his right eye. He was negative for anti-serum aquaporin 4 antibodies. A CSF examination showed normal values of leucocytes (1 /µl; 100% monocytes), protein (29.6 mg/dL) and glucose (55 mg/dL). The patient was treated with steroid therapy, which resulted in a full recovery. Thereafter, administration of PSL (5 mg/day) was continued. His eventual Expanded Disability Status Scale of Kurtzke was 2.0.
In February 2014, our inhouse cell-based assay1 showed that the patient was positive for serum anti-MOG antibodies (figure 1T–V). His antibody titres during the initial episode of encephalitis in mid-October 2008, during his relapse with optic neuritis in late August 2010 and during remission in late February 2014 were 4096x, 4096x and 512x, respectively.
Our case is unique in that the patient with encephalitis involving bilateral frontal cortical areas presented with paraparesis on admission. Common causes of acute and subacute non-traumatic paraplegia are inflammatory, vascular and neoplastic diseases of the thoracic cord, but there have been some rare non-myelopathic causes of paraplegia, such as polyradiculitis, hyperkalemic or hypokalemic paralysis, psychogenic paraplegia and parasagittal cortical syndrome.2 Although bilateral parasagittal cortical syndrome could be observed in cases of bilateral ischaemia in the anterior cerebral artery territories and fast-growing tumours in the parasagittal regions, encephalitis is not usually included in the differential diagnosis of paraplegia.2
The present case was positive for anti-MOG antibodies at the time of the diagnosis of encephalitis, ADEM-like lesions and unilateral optic neuritis. We considered that the anti-MOG antibody was involved in the ADEM-like lesions and optic neuritis in our case, since the clinical course and MRI findings were similar to those of the reported anti-MOG-antibody-positive cases. However, the pathogenetic involvement of anti-MOG antibodies in the unique encephalitis was unclear as neither demyelinating lesions in the brain biopsy nor elevated MBP levels in the CSF previously shown in anti-MOG-antibody-positive patients3 4 were confirmed in the present case. Recently, cases in which anti-NMDAR encephalitis and anti-MOG-antibody-associated demyelinating syndrome coexist have been reported.5 In our case, although no NMDAR, VGKC, AMPAR or GABA(B)R antibodies were detected, autoimmune encephalitis other than autoantibody-mediated encephalitis involving those antibodies might coexist with anti-MOG-antibody-associated demyelinating syndrome. Further study is needed to clarify the expanded spectrum of anti-MOG-antibody-associated diseases.