Anti-NMDAR encephalitis is the most common antibody-associated encephalitis and appears to be the leading cause of encephalitis in patients younger than 40 years old [3, 12]. As reported, approximately 45% of anti-NMDAR encephalitis patients over 18 years old and 9% of girls below 14 years old present with ovarian teratomas [11]. Clinical improvement following teratoma removal, anti-NMDAR encephalitis was herein considered paraneoplastic. Recently, several studies demonstrated that viral infection [6] is also a potential cause of anti-NMDAR encephalitis.
Anti-NMDAR encephalitis usually has an acute or subacute onset. Prodromal symptoms such as headache or flu-like symptoms occur frequently and approximately 50% of the anti-NMDAR encephalitis patients present fever during the course of the disease [3, 4, 7]. Neurological manifestations of anti-NMDAR encephalitis were typical of psychosis, behavioral changes, amnesia, decrease levels of consciousness, seizure and movement disorders [4,7]. Our patient mainly presented with headache, fever, and mild intermediate memory impairment. Cerebrospinal analysis revealed moderate lymphocytic pleocytosis, normal glucose and protein levels. These expressions are highly suggestive of viral or autoimmune encephalitis.
Despite the severity of signs and symptoms, brain MRI alterations are often subtle in more than half of patients [4], and in the remaining patients, abnormalities are present in the white and grey matter. White matter lesions have been reported in the medial temporal, frontal, parietal, occipital lobe, cingulate gyrus and corpus callosum, whereas grey matter lesions have been shown in the cerebral cortex, thalamus and basal ganglia [3, 4, 8-10]. Basal ganglia involvement was detected in less than 5% patients. Adding to the variability, affections of the cerebellum, brainstem and spinal cord have also been observed [4, 13]. Although minimal clinical neurological manifestations were found in our patient, brain MRI revealed diffuse, unenhanced lesions in white matter of the bilateral frontal lobes, left splenium of corpus callosum, and left basal ganglia. The extensive lesions in frontal and temporal lobes, and basal ganglia area, with mild mass effects seen in our patient have not been described previously. In differential diagnoses, demyelinating disorders (such as acute disseminated encephalomyelitis, tumefactive multiple sclerosis), cerebral gliomatosis or metastatic carcinoma were included.
To screen potential neoplasia, F18-FDG-PET was performed. F18-FDG-PET showed hypermetabolism in the cortex of the left frontal, temporal and parietal lobes and that of the right cerebellum, as well as hypometabolism in the left frontal basal ganglia and in the white matter lesions in bilateral frontal lobes. PET-CT results did not indicate any underlying tumors. Previous studies demonstrated hypermetabolism in anterior regions of frontal and temporal lobes compared to relative hypometabolism in posterior regions and hypermetabolism in basal ganglia in anti-NMDAR encephalitis [14, 15]. Our patient presented the same pattern of a relative anterior hypermetabolism in cortex but hypometabolism in left head of caudate nucleus. One possible explanation is that local edema had interrupted metabolism. In our patient, anti-NMDAR encephalitis was confirmed with its positive antibody in CSF. CSF antibody has a higher sensitivity (98.5-100%) in comparison with serum antibody (80.7-89.4%) [16].
Extreme delta brush, the distinctive EEG pattern in anti-NMDAR encephalitis, is present in only 30% of patients, whereas nonspecific slowing and disorganized background activities with or without epileptic waves were seen in most patients [17].
Noting that both clinical and EEG and brain imaging manifestations are nonspecific and that NMDA receptor encephalitis has a rather high occurrence, anti-NMDAR antibody in serum and cerebrospinal fluid should be detected in the patients suspected of cerebral nervous infections, glioma, demyelinating disorders, Hashimoto’s disease, primary or secondary central nervous system vasculitis etc. Once anti-NMDAR encephalitis is confirmed, immunotherapy and teratoma detection and removal should be quickly initiated. First line immunotherapies consist of a combination of corticosteroids and intravenous immunoglobulins, or plasma exchanges. For anti-NMDAR encephalitis patients without remarkable improvement or without tumor, second line immunotherapies, including mycophenolate mofetil, cyclophosphamide and rituximab, should be required [11]. Since the median length of time between symptoms onset and first relapse of anti-NMDAR encephalitis was 2 years, a minimum of 2 years of long-term clinical monitoring is necessary [12].
