VGKC antibody-associated encephalitis, microbleeds and progressive brain atrophy


Sir, Limbic encephalitis (LE) is an autoimmune disorder which can be of paraneoplastic or non-paraneoplastic origin. Antibodies (Abs) against voltage-gated potassium channels (VGKC-Abs) have recently been reported to be a possible cause of non-paraneoplastic LE responding to immunosuppressive therapy [1–3]. However, this type of LE may affect more than the limbic-restricted region, since some cases are described with a rapidly progressing cortical atrophy [2, 4]. A 79-year-old man was admitted to our hospital because of auditory hallucinations, agitation, and confusion with spatiotemporal disorientation. Neurological examination was otherwise normal. His medical history included surgery for epidermoid cancer of the left lung 5 years earlier which was considered in complete remission according to oncological investigations. At admission, blood serologies for viruses and Lyme disease were negative. Paraneoplastic Abs including anti-GAD, -Hu, -Ri, -YO, -CV2/CRMP, -Amphiphysin, and -Ma2 were negative. Anti-phospholipid Abs including anti-cardiolipin, anti-beta 2 glycoprotein, and lupus anticoagulant were negative. In addition, Protein C and S, antithrombine activity, and activated protein C resistance were normal; factor V Leiden and factor II mutations were absent. A CSF analysis revealed 50 WBC/ mm, elevated proteins to 0.83 g/L and oligoclonal bands matched in the serum. Serum VGKC-Abs were present at a high titer of 3,495 pM (normal range: 0–100, Radioimmuno assay detecting Kv1.1, 1.2 and 1.6 subtypes, laboratory of Prof. A. Vincent, Oxford, UK). There was no electromyographic sign of neuromyotonia, his Na level was normal in the serum and there was no antecedent of recent infective illness. The cerebral MRI at admission (Fig. 1a) showed a left hippocampus lesion with increased signal on coronal FLAIR sequences. Axial gradient echo T2-weighted MRI sequences showed the presence of cerebral microbleeds (CMBs) in cortical and subcortical regions which dramatically increased in number and size in the follow-up MRI performed 14 weeks later (Fig. 1b, c, f, g). This accumulation of CMBs was associated with signs of acute cortical necrosis which correlated with progressive brain atrophy (Fig. 1d, e, h, i). The clinical follow-up was characterized by partial seizures with secondary generalization, which required introduction of levetiracetam, as well as the development of memory impairment and aphasia (encoding ability 5 words: normal; verbal testing: 3/5 words immediate recall and 0/5 words 10 min later; visual testing: 2/5 objects immediate recall and 0/5 objects 10 min later; language testing revealed mostly a motor aphasia with alteration of the verbal fluency and some difficulties in comprehension of complex verbal orders). Clinical symptoms were eventually stabilized after high doses of IV corticosteroids and plasma exchanges (5 courses) were initiated (auditory hallucinations and agitation disappeared, but spatiotemporal disorientation, difficulties in comprehension of complex verbal V. Kapina S. Vulliemoz T. Landis F. Picard P. H. Lalive (&) Division of Neurology, Department of Neurosciences, University Hospital of Geneva and Faculty of Medicine, Rue Gabrielle Perret-Gentil 4, 1211 Geneva 14, Switzerland e-mail:

DOI: 10.1007/s00415-009-5370-5

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@article{Kapina2009VGKCAE, title={VGKC antibody-associated encephalitis, microbleeds and progressive brain atrophy}, author={Viktoria Kapina and M. Isabel Vargas and Serge Vulliemoz and Theodor Landis and Fabienne Picard and Patrice H Lalive}, journal={Journal of Neurology}, year={2009}, volume={257}, pages={466-468} }