Anti-NMDA receptor antibodies in a case of MELAS syndrome

Abstract

A 42-year-old man presented with new-onset headache, global aphasia, anteroand retrograde memory deficits, stereotypic behavior, agitation and an inappropriate foolish affect in July 2007. Immediate MRI revealed a T2w lesion in the left temporal lobe with cortical and subcortical involvement, compatible with encephalitis (Fig. 1). CSF analysis showed normal cell count and negative herpes simplex virus type I PCR while protein and lactate levels were elevated (protein: 1.36 g/l; normal: 0.15–0.45 g/l; lactate: 5.6 mmol/l; normal: 0.55–2.2 mmol/l). Repeated history taking revealed progressive bilateral hearing loss for 8 years. Additional MRI investigations showed a hyperintense appearance of the observed lesion in diffusion weighted images (DWI), mixed increased and decreased diffusion on apparent diffusion coefficient (ADC) maps, and a strong lactate peak in MR spectroscopy (Fig. 1). Further work-up revealed myopathic changes in several muscles on electromyography, elevated serum lactate during lactate stress test, hypertrophic cardiomyopathy, and signs of mitochondrial disease in muscle biopsy specimens (increased fuchsinophilia and COX-negative fibers). Family history was negative for mitochondrial disorders, but genetic analysis from leucocytes revealed a heteroplasmic m.3243A[G point mutation in mitochondrial DNA (heteroplasmy rate, 30%), compatible with a diagnosis of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). No other family members were tested. During the next few years, the patient developed focal epilepsy and progressive cognitive deficits. In 2010, he sustained a stroke-like episode of the left occipital cortex causing right homonymous hemianopia (Fig. 1). At this time, the initial clinical presentation was reconsidered and archived CSF/serum samples obtained 6 days after symptom onset in 2007 were analyzed for autoimmune antibodies. Antibodies were determined by means of a recombinant immunofluorescence assay employing NMDAR transfected HEK cells as described previously [1]. IgG-antibodies against NMDAR were detected in the patient’s serum at a titer of 1:32 (score 2 according to Irani et al. [4]). No antinuclear antibodies (ANA) or antibodies against further neuronal surface antigens (i.e., AMPA receptor, GABAb-receptor) or VGKC-complex were detected in the patient’s serum. On follow-up in 2010, NMDAR antibodies were negative both in serum and CSF. A body-CT revealed no malignancies. Taken together, our patient presented with symptoms compatible with a first manifestation of MELAS syndrome in 2007 [2]. The patient’s lesion in the left temporal lobe likely accounts for his aphasia, memory disturbances, and behavioral changes. Imaging characteristics suggest a stroke-like lesion associated with MELAS syndrome [3]. At the same time, however, the patient tested positive for anti-NMDAR antibodies that are considered highly specific C. Finke (&) H. Pruss F. Ostendorf L. Harms C. J. Ploner Department of Neurology, Charite-Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany e-mail: carsten.finke@charite.de