Background:&nbsp;Leucine‐rich glioma inactivated 1 (LGI1) antibody produces a syndrome of limbic encephalitis, hyponatremia, and facio‐brachial dystonic seizures that is non‐paraneoplastic and responsive to corticosteroids. Parkinsonism, tremor, and generalized chorea are rare manifestations of LGI1, but, when present, commonly accompany other signs of limbic encephalitis.Case Report:&nbsp;We present a case of LGI1‐related isolated chorea in a 53‐year‐old Japanese male. His chorea responded to high‐dose steroids, suggesting a potential role for this synaptic antibody in triggering chorea.Discussion:&nbsp;This case highlights a new treatable etiology of chorea.This article prompted a response letter:Vynogradova I, Savitski V, Heckmann JG. Hemichorea associated with CASPR2 antibody. Tremor Other Hyperkinet Mov. 2014; 4. doi:&nbsp;10.7916/D8VM49C5 The authors' response to the letter: Ramdhani RA, Frucht SJ. Reply to: hemichorea associated with CASPR2 antibody. Tremor Other Hyperkinet Mov. 2014; 4. doi: 10.7916/D8QV3JM0</p

Ritesh A. Ramdhani

Steven J. Frucht

Tremor and Other Hyperkinetic Movements

PubMed

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Isolated Chorea Associated with LGI1 Antibody

Background
Leucine-rich glioma inactivated 1 (LGI1) antibody produces a syndrome of limbic encephalitis, hyponatremia, and facio-brachial dystonic seizures that is non-paraneoplastic and responsive to corticosteroids. Parkinsonism, tremor, and generalized chorea are rare manifestations of LGI1, but, when present, commonly accompany other signs of limbic encephalitis.

Case Report
We present a case of LGI1-related isolated chorea in a 53-year-old Japanese male. His chorea responded to high-dose steroids, suggesting a potential role for this synaptic antibody in triggering chorea.

Discussion
This case highlights a new treatable etiology of chorea

Ramdhani, Ritesh A.

Frucht, Steven J.

Columbia University Academic Commons

Case ReportsIsolated Chorea Associated with LGI1 AntibodyRitesh A. Ramdhani1*& Steven J. Frucht11Movement Disorders Division, Icahn School of Medicine at Mount Sinai, New York, New York, United States of AmericaAbstractBackground: Leucine-rich glioma inactivated 1 (LGI1) antibody produces a syndrome of limbic encephalitis, hyponatremia, and facio-brachial dystonic seizuresthat is non-paraneoplastic and responsive to corticosteroids. Parkinsonism, tremor, and generalized chorea are rare manifestations of LGI1, but, when present,commonly accompany other signs of limbic encephalitis.Case Report: We present a case of LGI1-related isolated chorea in a 53-year-old Japanese male. His chorea responded to high-dose steroids, suggesting apotential role for this synaptic antibody in triggering chorea.Discussion: This case highlights a new treatable etiology of chorea.Keywords: LGI1 antibody, chorea, pulse steroids, reversibleCitation: Ramdhani RA, Frucht SJ. Isolated chorea associated with LGI1 antibody. Tremor Other Hyperkinet Mov. 2014; 4. doi: 10.7916/D8MG7MFC* To whom correspondence should be addressed. Email: Ritesh.Ramdhani@mssm.eduEditor: Elan D. Louis, Columbia University, United States of AmericaReceived: November 20, 2013 Accepted: December 10, 2013 Published: January 8, 2014Copyright: ’ 2014 Ramdhani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No Derivatives License, whichpermits the user to copy, distribute, and transmit the work provided that the original author(s) and source are credited; that no commercial use is made of the work; and that the work is notaltered or transformed.Funding: None.Financial Disclosures: None.Conflict of Interest: The authors report no conflict of interest.IntroductionLeucine-rich, glioma inactivated 1 (LGI1) is one of the synapticautoantigens targeted in voltage-gated potassium channel limbicencephalitis (LE).1 Antibodies to LGI1 produce a syndrome of LE(e.g., amnesia, confusion, hallucinations, and sleep disturbances),hyponatremia, and facio-brachial dystonic seizures.2 This autoimmunecondition is non-paraneoplastic3 and highly responsive to corticoster-oids.1,2,4,5 Movement disorders related to LGI1 are rare but includeparkinsonism,6 tremor,6 and generalized chorea7 but they uniformlyaccompany other signs of LE. Here, we present a case of steroid-responsive LGI1 with isolated chorea.Case reportA 53-year-old Japanese healthy male developed involuntary rightarm and leg movements 5 months prior to presentation. Onexamination (Video 1), there was mild chorea of the right arm, hand,and foot as well as slight involvement of the left arm that increasedwith distraction. A right milkmaid’s grip was present. There was nochorea of the face or impersistence of tongue protrusion. Muscle tone,reflexes, and coordination were intact. Walking activated his right-hand chorea.Cranial magnetic resonance images, serum electrolytes, completeblood count, hemoglobin A1C, antinuclear antibody, thyroid functiontests, and anti-cardiolipin antibody were normal. A serum paraneo-plastic panel revealed a positive LGI1 antibody. Computed tomo-graphy scans of the neck, chest, abdomen, and pelvis did not reveal anunderlying tumor and his cerebrospinal fluid analysis showed only amildly elevated protein. An electroencephalogram (EEG) was notindicated as the patient did not have facio-bracial dystonic seizures orVideo 1. Pre-treatment State. At rest, patient has mild chorea of the righthand and foot as well as of the fingers and toes on the left side, which enhanceduring distraction. Right-hand chorea increases when walking.Freely available onlineTremor and Other Hyperkinetic Movementshttp://www.tremorjournal.orgThe Center for Digital Research and ScholarshipColumbia University Libraries/Information Services1altered consciousness. After 5 days of intravenous pulse steroids(1000 mg of methylprednisolone daily) with a rapid oral taper, subtlechoreiform movements of the fingers and toes were observed only withdistractive maneuvers. This benefit continued to be sustained 1 monthpost steroid infusion (Video 2).DiscussionChorea has been reported as a feature of LGI1 primarily in thesetting of limbic encephalitis.7 To our knowledge, this is the first reportof LGI1-associated chorea devoid of other classic features such as LE,hyponatremia, and seizures. Like most LGI1-related LE, our patientdid not have a tumor and responded robustly to pulse steroid infusions.Our patient’s primary asymmetric symptomatology parallels withother patients with facio-brachial dystonic seizures (FBDS) from LGI1.Irani et al.2 reported that 26 of 29 patients with FBDS developed it priorto the onset of LE, with a median delay of 36 days. Neither amnesia norconfusion developed in our patient 7 months from the onset of hissymptoms as he continued to work and perform all activities of dailyliving independently. This suggests that chorea is unlikely antecedent toLE. Positron emission tomography and single photon emission computedtomography imaging in this cohort revealed abnormalities in the basalganglia. Though the pathophysiology of chorea in LGI1 remainsunclear, it is known that LGI1 binds to proteins associated with Kv1potassium channels8 and modulates synaptic excitability.9,10 Therefore,we postulate that the synaptic antibodies may directly bind to potassiumchannel elements in the indirect pathway altering the circuitry. Theresponse to steroid therapy is further supportive of this possibility.This case highlights a new, treatable etiology of chorea, whichshould be considered when a clear structural or metabolic abnormalityis not found.References1. Lai M, Huijbers MG, Lancaster E, et al. Investigation of LGI1 as theantigen in limbic encephalitis previously attributed to potassium channels: acase series. Lancet Neurol 2010;9:776–785, doi: http://dx.doi.org/10.1016/S1474-4422(10)70137-X.2. Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizuresprecede Lgi1 antibody limbic encephalitis. Ann Neurol 2011;69:892–900, doi:http://dx.doi.org/10.1002/ana.22307.3. Rubio-Agusti I, Salavert M, Bataller L. Limbic encephalitis and relatedcortical syndromes. Curr Treat Options Neurol 2013;15:169–184, doi: http://dx.doi.org/10.1007/s11940-012-0212-7.4. Thieben MJ, Lennon VA, Boeve BF, et al. Potentially reversibleautoimmune limbic encephalitis with neuronal potassium channel antibody.Neurology 2004;62:1177–1182, doi: http://dx.doi.org/10.1212/01.WNL.0000122648.19196.02.5. Vincent A, Buckley C, Lang B, et al. Clinical spectrum of voltage-gatedpotassium channel autoimmunity. Neurology 2009;72:99; author reply 99–100,doi: http://dx.doi.org/10.1212/01.wnl.0000339405.94708.8d6. Tan KM, Lennon VA, Klein CJ, et al. Clinical spectrum of voltage-gatedpotassium channel autoimmunity. Neurology 2008;70:1883–1890, doi: http://dx.doi.org/10.1212/01.wnl.0000312275.04260.a0.7. Tofaris GK, Irani SR, Cheeran BJ, et al. Immunotherapy-responsivechorea as the presenting feature of LGI1-antibody encephalitis. Neurology 2012;79:195–196, doi: http://dx.doi.org/10.1212/WNL.0b013e31825f0522.8. Irani SR, Alexander S, Waters P, et al. Antibodies to Kv1 potassiumchannel-complex proteins leucine-rich, glioma inactivated 1 protein andcontactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome andacquired neuromyotonia. Brain 2010;133:2734–2748, doi: http://dx.doi.org/10.1093/brain/awq213.9. Zhou YD, Lee S, Jin Z, et al. Arrested maturation of excitatory synapsesin autosomal dominant lateral temporal lobe epilepsy. Nat Med 2009;15:1208–1214, doi: http://dx.doi.org/10.1038/nm.2019.10. Irani SR, Pettingill P, Kleopa KA, et al. Morvan syndrome: clinical andserological observations in 29 cases. Ann Neurol 2012;72:241–255, doi: http://dx.doi.org/10.1002/ana.23577.Video 2. One Month Post Steroid Treatment. There are subtle choreiformmovements of the fingers and toes when distracted. There is no chorea at rest orwhen walking.Ramdhani RA, Frucht SJ LGI1-Induced Reversible ChoreaTremor and Other Hyperkinetic Movementshttp://www.tremorjournal.orgThe Center for Digital Research and ScholarshipColumbia University Libraries/Information Services2

English

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;133:2734–2748, doi: http://dx.doi.org/

Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy.

Clinical spectrum of voltage-gated potassium channel autoimmunity.

Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology 2009;72:99; author reply 99–100,

Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis.

Immunotherapy-responsive chorea as the presenting feature of LGI1-antibody encephalitis.

Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol 2010;9:776–785, doi: http://dx.doi.org/10.1016/

Limbic encephalitis and related cortical syndromes.

Potentially reversible autoimmune limbic encephalitis with neuronal potassium channel antibody. Neurology 2004;62:1177–1182,

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Isolated Chorea Associated with LGI1 Antibody

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