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Bi-insular cortical involvement in anti-NMDA-receptor encephalitis – a case report
© The Author(s). 2016
Received: 28 April 2016
Accepted: 29 July 2016
Published: 8 August 2016
Anti-NMDA-receptor encephalitis is an immune-mediated inflammatory disorder of the central nervous system. Brain MRI is unremarkable in at least 50 % of patients and highly variable in the remaining patients with signal abnormalities in different brain regions. Only scarce reports exist on other imaging modalities.
A 31-year-old woman sub-acutely developed psychosis, behavioural changes, amnesia, alternating states of agitation and mutism, fever and epileptic seizures. Clinically suspected diagnosis of anti-NMDA-receptor encephalitis was confirmed by the detection of anti-NMDA receptor antibodies in CSF and serum. During the acute phase, brain MRI abnormalities were found in both insular cortices and hippocampi, whereas F18-FDG-PET showed hypermetabolism bilaterally in insular and prefrontal cortex. After resection of the underlying ovarian teratoma and with multimodal immunotherapy the patient substantially improved reaching a modified Rankin Scale score of 2 after 3 months. At follow-up, both hippocampi were still affected on MRI, whereas insular cortex appeared normal; however, both regions showed prominent glucose hypometabolism.
Here, we report bi-insular cortical abnormalities on MRI and F18-FDG-PET in a patient with anti-NMDA-receptor encephalitis during the acute phase and after clinical improvement.
Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is an immune-mediated inflammatory disorder of the central nervous system first described in 2007 . Patients usually present with a clinical syndrome including psychosis, behavioural changes, amnesia and epileptic seizures, frequently followed by dyskinesia and decreased levels of consciousness . The disease has a female predominance and is associated with an underlying tumour, mostly ovarian teratoma, in approximately 50 % of cases . Patients are treated with tumour resection if applicable and immunotherapy (corticosteroids, intravenous immunoglobulins and/ or plasma exchange, and in case of treatment failure cyclophosphamide and/ or rituximab) . About 75 % of patients fully recover or show mild disability, the remaining patients suffer from severe disability or die. The main predictor of good outcome is the early initiation of treatment .
Diagnosis is obtained by the detection of anti-NMDAR antibodies in cerebrospinal fluid (CSF) and/ or serum . Besides that, diagnostic work-up includes further examinations such as routine CSF analysis, tumour screening and brain imaging . Brain MRI is unremarkable in 50–90 % of patients [2, 3, 5]; in the remaining patients abnormalities are highly variable evolving in the white and grey matter . White matter lesions have been reported in the medial temporal, frontal, parietal, occipital lobe [1, 4, 5, 7, 8], cingulate gyrus [9, 10] and corpus callosum , whereas grey matter has been shown to be involved in cerebral cortex [1, 4, 9] and certain nuclei such as thalamus  or basal ganglia [4, 12]. In addition, affections of the cerebellum [4, 9, 13] and brainstem [4, 9] have been observed. MRI alterations are typically subtle despite the severity and duration of signs and symptoms .
Only scarce evidence exists on other imaging modalities. F18-FDG-PET can reveal pathological changes even when MRI is normal . Glucose hypermetabolism has been found in frontotemporal areas [5, 8–10, 14], in the cerebellum [5, 8, 9], brainstem , thalamus and basal ganglia .
In the following, we present a case of anti-NMDAR encephalitis with bi-insular cortical abnormalities on MRI and F18-FDG-PET during the acute phase of the disease and after substantial clinical improvement.
A 31-year-old woman presented at the hospital’s emergency department with prominent, sub-acutely evolving psychiatric signs and symptoms including bizarre behaviour, delusional thoughts and alternating states of agitation and mutism. Besides that, she showed short-term amnesia, fever and complex epileptic seizures. Her family reported that she had already complained about insomnia and general discomfort for the past 2 weeks; otherwise there was no history of any diseases and no use of concomitant medication. The neurological examination revealed no further abnormalities, especially no meningism and no focal deficits.
After tumour resection and multimodal immunotherapy (plasmapheresis for 4 days followed by intravenously applied corticosteroids over 5 days at a total dose of 4 g) the patient improved substantially. In serum samples, anti-NMDAR antibody titres decreased from 1:160 to 1:20 . After 3 months the patient still had slight disability, was able to look after her own affairs without assistance, but was unable to carry out all previous activities, mainly due to memory deficits (corresponding to a modified Rankin Scale score of 2). At this point of time insular abnormalities on diffusion- and T2/ FLAIR-weighted MRI had disappeared, whereas hippocampal FLAIR/ T2-hyperintensity remained (Fig. 1b). In both areas prominent glucose hypometabolism was observed; glucose-metabolism in prefontal cortex was normal (Fig. 2b).
Here, we report bi-insular cortical involvement in anti-NMDA-receptor encephalitis  as shown by structural and metabolic abnormalities. The striking correlation between initial MRI findings (T2/ FLAIR hyperintensity and diffusion-restriction, respectively) and initial F18-FDG-PET hypermetabolism that was followed by a prominent hypometabolism suggests that structural disruption and not only functional changes in brain metabolism results in medium-term brain dysfunction .
There are some considerations with regard to different, longitudinally performed imaging modalities in patients with anti-NMDAR encephalitis. In general, imaging abnormalities reflect a present disruption within brain areas, which might improve  or even disappear with clinical improvement, as this was the case in our patient. However, it has to be highlighted that a significant proportion of patients shows normal routine MRI during the acute phase of the disease and that structural changes might only be detected by more sophisticated MRI methods such as volumetry, analysis of microstructural integrity or resting state functional connectivity [17, 18]. Timing of imaging is another crucial issue. Whereas MRI abnormalities might resolve over time, hypermetabolic areas on F18-FDG-PET during the acute phase of the disease typically turn into hypometabolic state during the early recovery phase. During this time, patients have already clinically improved but are still disabled, as this was also the case in our patient. After a longer follow-up glucose hypometabolism might be alleviated and accompanied by further clinical improvement .
In conclusion, this case confirms that there exists a serial changing brain pattern on MRI and F18-FDG-PET and depicts involvement of insular cortex in patients with anti-NMDA-receptor encephalitis.
CSF, cerebrospinal fluid; F18-FDG-PET, 18-Fluoro-deoxyglucose positron emission tomography; MRI, magnetic resonance imaging; NMDAR, N-methyl-D-aspartate-receptor
There was no funding of the study.
Availability of data and materials
All relevant data supporting the conclusions of this case report are displayed within this manuscript. Complete MRI and PET scans can be provided by the corresponding author upon request.
HH as the principal author is responsible for study concept, interpretation of the data and drafting the manuscript. CU qualifies as author based on his contribution towards drafting the manuscript and interpretation of the data. AG qualifies as author based on her contribution to draft the manuscript. IV, RB, RH and BP qualify as authors due to their contribution to revise the manuscript for intellectual content. MR qualifies as author based on her contribution to the acquisition and analysis of data. ES qualifies as author based on his contribution towards interpretation of the data and revising the manuscript for intellectual content. All authors have read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the corresponding author.
Ethics approval and consent to participate
Ethics approval was not obtained, as not necessary for reports on routinely treated patients, based on Austria’s legislation.
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