Print version ISSN 0004-282X
Arq. Neuro-Psiquiatr. vol.69 no.6 São Paulo Dec. 2011
Declínio cognitivo subagudo, hiponatremia e lesões temporais mesiais: uma apresentação típica de encefalite límbica associada a anticorpos contra canais de potássio voltagem dependentes (VGKC)
Thais Saccardi; José Luiz Pedroso; Tenille Bernardino; Orlando G.P. Barsottini; Henrique Ballalai Ferraz
Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo SP, Brazil
For many years, several reports have called attention for non-viral limbic encephalitis (LE), particularly with paraneoplastic etiology. However, an increasing number of data have demonstrated that some of those disorders are immune-mediated with antibodies to voltage-gated potassium channels (VGKC)1.
Herein, we present a case of VGKC antibody-associated LE and discuss the main phenotypic and imaging features of this unusual disease.
A 50-year-old man presented to our hospital with three months history of progressive personality change, sleep disturbance, memory impairment, visual hallucinations and seizures. Neurological examination showed disorientation, cognitive impairment (Mini Mental State Examination: 13) and memory dysfunction. Blood tests showed hyponatremia - 130 mmol/L (135-145 mmol/L). Thyroid function, antibodies and serologic tests were normal. Cerebrospinal fluid showed high level of proteins (558 mg/dL) and mild lymphocytic pleocytosis. Brain magnetic resonance imaging (MRI) disclosed bilateral T2 and FLAIR hyperintensity of mesial temporal lobes (Figure). Cancer investigation resulted negative. VGKC serum level was higher than 650 pmol/L (normal range less than 450 pmol/L). These findings confirmed the diagnosis LE with VGKC antibodies. Methylprednisolone was started, with partial improvement. Three weeks later, immunoglobulin 0.4 g/Kg daily for five consecutive days was initiated. One week after immunoglobulin therapy, the patient presented a clear improvement and achieved a MMSE score of 26.
Recent data have described LE caused by antibodies to VGKC, a specific cell-membrane antigen1,2. Other antibodies related to LE include NMDA, AMPAR and GABA3,4. Although LE is frequently related to auto-immune etiology, a paraneoplastic syndrome is found in 30% of the cases3. When hyperhidrosis, autonomic dysfunction, psychiatric symptoms and neuromyotonic discharges are present, Morvan syndrome must be suspected5.
Although often unrecognized, the neurological spectrum of VGKC antibody-associated LE includes seizures and neuropsychiatric symptoms, ranging from alterations in memory, behavior, and cognition1. Neuroimaging shows bilateral hyperintense sign in mesial temporal lobe1. Imaging differential diagnosis includes: herpetic and paraneoplastic encephalitis, status epilepticus, other immunomediated encephalitis (e.g., anti-NMDA, anti-VGKC) and Alzheimer disease due to the S170F mutation in the presenilin 1 (PS-1) gene2. Hyponatremia occurred in 60% of patients and might be attributed to the expression of leucine-rich, glioma-inactivated 1 (LGI1) in the hypothalamus2.
Recently, Lai et al. described that LGI1 is the autoantigen associated with LE previously attributed to VGKC antibodies. Several patients with the typical syndrome presented negative VGKC and positive LGI1 antibodies2. The majority of the patients favorably respond to immunotherapy. Administration of human immunoglobulin or plasma exchange is the first line treatment. Methylprednisolone can also be effective. Several patients required chronic therapy on lower dose steroids, with or without azathioprine5.
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2. Lai M, Huijbers MGM, Lancaster E, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 2010;9:776-785. [ Links ]
3. Graus F, Saiz A, Lai M, et al. Neuronal surface antigen antibodies in limbic encephalitis: clinical: immunologic associations. Neurology 2008;16: 930-936. [ Links ]
4. Shimazaki H, Ando Y, Nakano I, Dalmau J. Reversible limbic encephalitis with antibodies against the membranes of neurones of the hyppocampus. J Neurol Neurosurg Psychiatry 2007;78:324-325. [ Links ]
5. Merchut MP. Manegement of voltage-gated potassium channel antibody disorders. Neurol Clin 2010;28:941-959. [ Links ]
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Received 15 May 2011.
Received in final form 19 July 2011.
Accepted 26 July 2011.