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Table of Contents    
Year : 2016  |  Volume : 64  |  Issue : 6  |  Page : 1321-1323

Limbic encephalitis associated with anti-leucine-rich glioma-inactivated-1 protein antibodies in a child

1 Department of Pediatric Neurology, Cukurova University Faculty of Medicine, Adana, Turkey
2 Department of Pediatric Immunology, Cukurova University Faculty of Medicine, Adana, Turkey

Date of Web Publication11-Nov-2016

Correspondence Address:
Faruk Incecik
Department of Pediatric Neurology, Cukurova University Faculty of Medicine, Adana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.193776

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How to cite this article:
Incecik F, Hergüner OM, Besen S, Yılmaz M, Altunbasak S. Limbic encephalitis associated with anti-leucine-rich glioma-inactivated-1 protein antibodies in a child. Neurol India 2016;64:1321-3

How to cite this URL:
Incecik F, Hergüner OM, Besen S, Yılmaz M, Altunbasak S. Limbic encephalitis associated with anti-leucine-rich glioma-inactivated-1 protein antibodies in a child. Neurol India [serial online] 2016 [cited 2021 Jan 23];64:1321-3. Available from:


Limbic encephalitis (LE) is a neurological syndrome that may present in association with paraneoplastic and nonparaneoplastic causes. In nonparaneoplastic LE, antibodies may be generated against the cell membrane or intracellular antigens. These antibodies are anti-glutamic acid decarboxylase (GAD), anti-N-methyl-D-aspartate-receptor (NMDAR), anti-voltage-gated potassium channels (VGKC) complex, and anti-γ-aminobutyric acid receptor antibodies.[1] Antibodies against leucine-rich glioma-inactivated-1 protein (LGI1), one of the specific targets of VKGC-complex antibodies may also exist.[2] LE associated with anti-LGI1 antibody is a rare inflammatory brain disease characterized by acute or subacute onset of confusion, cognitive impairment, faciobrachial dystonic seizures (FBDS), and behavioral and psychiatric disturbances. Neuroimaging abnormalities involving the mesial temporal lobes and other areas of the limbic system may be identified.[2]

An 8-year-old girl was admitted to the hospital because of behavioral changes, hallucinations, confusion, and seizures. One month before the onset of her complaints, she had an upper respiratory tract infection. The initial symptoms were behavioral changes, hallucinations, and confusion. Fifteen days after the initial symptoms, seizures occurred. Other past medical history was unremarkable; she had no family history of seizures, neurological, or immune disorders. On neurological examination, she had agitation, confusion but no loss of consciousness. The remainder of the physical and neurological examination was normal. On laboratory examination, complete blood count, renal and liver function tests, and thyroid function tests were normal. Serum sodium level was 135 mEq/L. The magnetic resonance imaging of brain showed hyperintense lesions in the right hippocampal region [Figure 1]. Electroencephalogram revealed epileptiform activity in the right frontotemporal region. Cerebrospinal fluid (CSF) sample showed normal protein and cellular content. Serological and CSF assays for infectious agents, including viral etiologies, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Lyme disease, were negative. A serological panel for autoimmune disorders including antinuclear antibodies, double-stranded DNA antibody, rheumatoid factor, and complement levels was negative. On the 15th day of hospitalization, antineuronal antibody tests were performed in serum for suspected LE. For the detection of anti-LGI1, cell-based indirect immunofluorescence antibody assay technique was used. Anti-LGI1 antibodies were positive. No evidence of neoplasm was found on whole body positron emission tomography–computed tomography. On the basis of the clinical and laboratory findings, the patient was diagnosed as LE with anti-LGI1 antibodies. Levetiracetam therapy was started for complex partial with secondary generalized seizures. A dose of intravenous immunoglobulins (IVIg) 0.4 g/kg/day was administered for 5 days for the presumed diagnosis of nonparaneoplastic LE. After IVIg treatment, the neurological condition did not completely improve. Then, we started pulse prednisolone treatment (600 mg methylprednisolone/day IV bolus for 3 days), followed by oral prednisolone (1 mg/kg/day). After combination therapy, her neurological symptoms gradually recovered.
Figure 1: Brain magnetic resonance imaging shows increased signal in the right medial temporal lobe

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A recent discovery showed that several forms of encephalitis resulted from antibodies against neuronal proteins. This has changed the approach to the diagnosis and treatment of these disorders. Autoimmune encephalitis is increasingly being diagnosed also in children with antibodies to NMDAR, and in some with antibodies to the VGKC-complex protein or other central nervous system (CNS) antigens such as GAD.[1] Although antibodies against VGKC-complex are occasionally detected in childhood encephalitis, antigens of these antibodies are neither LGI1 nor contactin-associated protein-2 (CASPR2).[2] Children with VGKC-complex antibodies presented either with LE and prolonged seizures or with a less specific encephalopathy syndrome with varying degrees of seizures and psychiatric features.

LGI1 is one of the synaptic autoantigens targeted in VGKC.[2],[3] LGI1 protein has a significant role in synaptic transmission by regulating the presynaptic Kv1.1 and Kv1.2 subunits and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and myelination. LGI1 antibodies may prevent binding of LGI1 to the receptors that regulate, disrupt currents mediated by Kv1.1 and Kv1.2, and impair AMPA receptor functions.[4] It is the most frequent antibody associated with immune-mediated LE in adults. LGI1 autoantibodies are associated with various neurologic conditions, such as hyponatremia, FBDS, psychiatric symptoms, cognitive impairment, and various types of seizures including myoclonic-like movements.[2],[5] Age of the patients varies between 30 and 80 years and most do not have cancer. It seems to have a higher predilection for males in literature.[5] In literature, there are rare reports about LGI1 antibody being associated with predominantly peripheral nerve symptoms. Both LGI1 and CASPR2 antibodies were detected in a 2-year-old boy with Guillain-Barre syndrome (GBS). CASPR2 was found in another 6-year-old child with GBS. Both patients made a complete clinical recovery.[6] In another report, double LGI1 and CASPR2 were reported in adult patients with Morvan's syndrome and acquired neuromyotonia.[7] LGI1 is a secreted neuronal protein that interacts with the presynaptic and postsynaptic proteins ADAM23 and ADAM22 that act to modulate synaptic transmission. The tissue distribution and function of VGKC-complex antibodies that make it a biologically plausible autoimmune target in peripheral nerves should be determined in further studies. Anti-LGI1-associated encephalitis has not been reported till date in children. To the best of our knowledge, our patient is the first reported child who has LE associated with anti-LGI1.

Neurological abnormalities associated with anti-LGI1 antibodies usually respond rapidly to immunotherapy. Variable regimens of steroid, IVIg, and plasma exchange have been administered, mostly with favorable results in literature.[8]

In conclusion, in the last few years, antibodies to ion channels and growing number of receptors have been identified in children with acute or subacute onset of CNS syndromes. To our knowledge, this is the first described case of LE associated with anti-LGI1 in children. An early diagnosis of this rare disease is important because of the potential response to the treatment. In encephalitic processes of unclear etiology, autoimmune mechanisms should be considered when symptoms develop rapidly, accompanied with signs of inflammation in the CSF and/or neuroimaging studies.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Armangue T, Petit-Pedrol M, Dalmau J. Autoimmune encephalitis in children. J Child Neurol 2012;27:1460-9.  Back to cited text no. 1
Agazzi P, Bien CG, Staedler C, Biglio V, Gobbi C. Over 10-year follow-up of limbic encephalitis associated with anti-LGI1 antibodies. J Neurol 2015;262:469-70.  Back to cited text no. 2
Hacohen Y, Wright S, Waters P, Agrawal S, Carr L, Cross H, et al. Paediatric autoimmune encephalitis. Clinical features, laboratory investigations and outcome in patients without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 2013;84:748-55.  Back to cited text no. 3
Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology 2011;77:179-89.  Back to cited text no. 4
Suleiman J, Brenner T, Gill D, Brilot F, Antony J, Vincent A, et al. VGKC antibodies in pediatric encephalitis presenting with status epilepticus. Neurology 2011;76:1252-5.  Back to cited text no. 5
Rosch RE, Bamford A, Hacohen Y, Wraige E, Vincent A, Mewasingh L, et al. Guillain-Barré syndrome associated with CASPR2 antibodies: Two paediatric cases. J Peripher Nerv Syst 2014;19:246-9.  Back to cited text no. 6
Irani SR, Alexander S, Waters P, Kleopa KA, Pettingill P, Zuliani L, et al. Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. Brain 2010;133:2734-8.  Back to cited text no. 7
Wong SH, Saunders MD, Larner AJ, Das K, Hart IK. An effective immunotherapy regimen for VGKC antibody-positive limbic encephalitis. J Neurol Neurosurg Psychiatry 2010;81:1167-9.  Back to cited text no. 8


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