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Hypoglutamatergic state is associated with reduced cerebral glucose metabolism in anti-NMDA receptor encephalitis: a case report.

Endres D, Perlov E, Stich O, Rauer S, Maier S, Waldkircher Z, Lange T, Mader I, Meyer PT, van Elst LT - BMC Psychiatry (2015)

Bottom Line: Despite the long course of disease, immunosuppressive therapy with methylprednisolone and azathioprine led to almost complete remission of clinical symptoms.First, it illustrates that a very good outcome is possible even if adequate therapy is started only 21 months after the onset of severe symptoms.These findings, contradictory at first glance, can be integrated within the model of excitatory/inhibitory imbalance and local area network inhibition.

View Article: PubMed Central - PubMed

Affiliation: Section of Experimental Neuropsychiatry, Department for Psychiatry& Psychotherapy, University Medical Center Freiburg, Hauptstr. 5, 79104, Freiburg, Germany. dominique.endres@uniklinik-freiburg.de.

ABSTRACT

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was first described in 2005 in association with ovarian teratoma. The diagnostic workup of this common autoimmune encephalitis includes cerebrospinal fluid analysis, electroencephalography, magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (FDG-PET). In addition to standard diagnostics, we performed metabolic investigations using proton magnet resonance spectroscopy ((1)H-MRS).

Case presentation: We describe the case of a non-limbic anti-NMDAR encephalitis with a long course of disease (21 months). Laboratory diagnostics showed antibodies against NMDAR; an MRI revealed unspecific findings. (1)H-MRS indicated a hypoglutamatergic state in the left prefrontal cortex associated with a left hemispherical hypometabolism on FDG-PET. Despite the long course of disease, immunosuppressive therapy with methylprednisolone and azathioprine led to almost complete remission of clinical symptoms. Clinical improvement developed in parallel with remarkable normalization of cerebral glucose metabolism on FDG-PET.

Conclusion: This case of long-lasting extra-limbic anti-NMDAR encephalitis is of high clinical relevance. First, it illustrates that a very good outcome is possible even if adequate therapy is started only 21 months after the onset of severe symptoms. Second, it provides valuable insights into the pathophysiology of such anti-NMDAR encephalitis; these insights prove that anti-NMDAR encephalitis is linked not only to hyperglutamatergic signals but also to hypoglutamatergic states. These findings, contradictory at first glance, can be integrated within the model of excitatory/inhibitory imbalance and local area network inhibition.

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Magnet resonance imaging (MRI) findings. MRI only shows a moderate perisylvic/temporal accentuated atrophy
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Fig1: Magnet resonance imaging (MRI) findings. MRI only shows a moderate perisylvic/temporal accentuated atrophy

Mentions: In the CSF analysis, we found a blood–brain barrier disturbance (protein: 561 mg/l, albumin-quotient: 8.7), normal cell count (1/μl), and no intrathecal immunoglobulin synthesis. Serological screening for antibodies against neuronal cell surface antigens showed antibodies against the NMDA receptor. The analysis was performed in the reference laboratory at the Weatherall Institute of Molecular Medicine at John Radcliffe Hospital (Oxford, UK). EEG analysis showed an intermittent delta focus over the right central areas. In an additional independent component analysis of the EEG, we were able to describe three components: 1) right and left frontotemporal delta waves; 2) a deep right temporal generator; and 3) a central component including theta frequencies. MRI showed no specific findings; especially the hippocampal regions and structures of limbic system were without pathological findings. Moderate perisylvic/temporal accentuated atrophy was found (Fig. 1). On FDG-PET, global cortical hypometabolism of the left hemisphere was detected. A less pronounced hypometabolism was also detected on the right side, particularly of the temporal lobe. Cerebellar hypometabolism was found predominantly on the right side (most likely indicating crossed cerebellar diaschisis) (Fig. 2). 1H-MRS was performed in the prefrontal cortex (PFC) on both sides, using the standard single-voxel spectroscopy (voxel size 8 ml) Table 1. For spectroscopic analysis, the well-established and investigator-independent LCModel (linear combination of model spectra) algorithm was used (www.s-provencher.com/pages/lcmodel.shtml) [21, 22]. In the PFC of the hypometabolic left hemisphere, we found distinct lower Glx concentrations compared with the opposite side. Glx/Cr ratios were also significantly decreased.Fig. 1


Hypoglutamatergic state is associated with reduced cerebral glucose metabolism in anti-NMDA receptor encephalitis: a case report.

Endres D, Perlov E, Stich O, Rauer S, Maier S, Waldkircher Z, Lange T, Mader I, Meyer PT, van Elst LT - BMC Psychiatry (2015)

Magnet resonance imaging (MRI) findings. MRI only shows a moderate perisylvic/temporal accentuated atrophy
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522073&req=5

Fig1: Magnet resonance imaging (MRI) findings. MRI only shows a moderate perisylvic/temporal accentuated atrophy
Mentions: In the CSF analysis, we found a blood–brain barrier disturbance (protein: 561 mg/l, albumin-quotient: 8.7), normal cell count (1/μl), and no intrathecal immunoglobulin synthesis. Serological screening for antibodies against neuronal cell surface antigens showed antibodies against the NMDA receptor. The analysis was performed in the reference laboratory at the Weatherall Institute of Molecular Medicine at John Radcliffe Hospital (Oxford, UK). EEG analysis showed an intermittent delta focus over the right central areas. In an additional independent component analysis of the EEG, we were able to describe three components: 1) right and left frontotemporal delta waves; 2) a deep right temporal generator; and 3) a central component including theta frequencies. MRI showed no specific findings; especially the hippocampal regions and structures of limbic system were without pathological findings. Moderate perisylvic/temporal accentuated atrophy was found (Fig. 1). On FDG-PET, global cortical hypometabolism of the left hemisphere was detected. A less pronounced hypometabolism was also detected on the right side, particularly of the temporal lobe. Cerebellar hypometabolism was found predominantly on the right side (most likely indicating crossed cerebellar diaschisis) (Fig. 2). 1H-MRS was performed in the prefrontal cortex (PFC) on both sides, using the standard single-voxel spectroscopy (voxel size 8 ml) Table 1. For spectroscopic analysis, the well-established and investigator-independent LCModel (linear combination of model spectra) algorithm was used (www.s-provencher.com/pages/lcmodel.shtml) [21, 22]. In the PFC of the hypometabolic left hemisphere, we found distinct lower Glx concentrations compared with the opposite side. Glx/Cr ratios were also significantly decreased.Fig. 1

Bottom Line: Despite the long course of disease, immunosuppressive therapy with methylprednisolone and azathioprine led to almost complete remission of clinical symptoms.First, it illustrates that a very good outcome is possible even if adequate therapy is started only 21 months after the onset of severe symptoms.These findings, contradictory at first glance, can be integrated within the model of excitatory/inhibitory imbalance and local area network inhibition.

View Article: PubMed Central - PubMed

Affiliation: Section of Experimental Neuropsychiatry, Department for Psychiatry& Psychotherapy, University Medical Center Freiburg, Hauptstr. 5, 79104, Freiburg, Germany. dominique.endres@uniklinik-freiburg.de.

ABSTRACT

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was first described in 2005 in association with ovarian teratoma. The diagnostic workup of this common autoimmune encephalitis includes cerebrospinal fluid analysis, electroencephalography, magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (FDG-PET). In addition to standard diagnostics, we performed metabolic investigations using proton magnet resonance spectroscopy ((1)H-MRS).

Case presentation: We describe the case of a non-limbic anti-NMDAR encephalitis with a long course of disease (21 months). Laboratory diagnostics showed antibodies against NMDAR; an MRI revealed unspecific findings. (1)H-MRS indicated a hypoglutamatergic state in the left prefrontal cortex associated with a left hemispherical hypometabolism on FDG-PET. Despite the long course of disease, immunosuppressive therapy with methylprednisolone and azathioprine led to almost complete remission of clinical symptoms. Clinical improvement developed in parallel with remarkable normalization of cerebral glucose metabolism on FDG-PET.

Conclusion: This case of long-lasting extra-limbic anti-NMDAR encephalitis is of high clinical relevance. First, it illustrates that a very good outcome is possible even if adequate therapy is started only 21 months after the onset of severe symptoms. Second, it provides valuable insights into the pathophysiology of such anti-NMDAR encephalitis; these insights prove that anti-NMDAR encephalitis is linked not only to hyperglutamatergic signals but also to hypoglutamatergic states. These findings, contradictory at first glance, can be integrated within the model of excitatory/inhibitory imbalance and local area network inhibition.

Show MeSH
Related in: MedlinePlus