Background: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a rare entity. Its typical features are seizures, faciobrachial dystonic seizures (FBDS), cognitive impairment, and personality changes.

Case report: We report the case of a 66-year-old man with an unusual presentation, consisting of two types of FBDS, one starting in the foot and the other consisting of asynchronous myoclonic and dystonic jerks of the face triggered by noise and chin stimulation. The patient displayed no personality changes or cognitive impairment.

Discussion: LGI1 encephalitis is a heterogeneous disease. Many different forms of FBDS may be observed, and these seizures can be the only symptom. This type of encephalitis should be suspected in presenting very frequent episodic events with dystonic features, regardless of the part of the body affected

Benaiteau, Marie

Bost, Chloé

Courbon, Christine Brefel

Dupouy, Julia

Moreau, Marion Simonetta

Ory Magne, Fabienne

Rachdi, Amine

Rascol, Olivier

Columbia University Academic Commons

1Case ReportsLeucine-Rich Glioma-Inactivated 1 Encephalitis: Broadening the SphereAmine Rachdi1, Julia Dupouy2, Marie Benaiteau2, Chloé Bost3, Marion Simonetta Moreau2, Christine Brefel Courbon2, Olivier Rascol1,2 & Fabienne Ory Magne2*1Centre d’investigations Clinique, CHU Toulouse, Toulouse, FR, 2Service de neurologie B8, CHU Toulouse, Toulouse, FR, 3Service d’immunologie, CHU Toulouse, Toulouse, FRIntroductionThe diagnosis of  autoimmune encephalitis with movement disorders can be challenging,1 particularly for atypical presentations, but prompt diagnosis is required to reduce delays in treatment. Leucine-rich glio-ma-inactivated 1 (LGI1) encephalitis is a rare disease, generally associated with seizures, asymmetric faciobrachial dystonic seizures (FBDS), person-ality changes and rapidly progressing cognitive impairment.2 We report an unusual presentation of  LGI1 encephalitis limited to two atypical types of  FBDS: (1) principally dystonic jerks beginning in one foot, (2) occa-sional, asynchronous reflex myoclonus and dystonic jerks of  the face, trig-gered by noise and chin stimulation. The patient presented no other symptoms, and no cognitive decline was detected, despite late diagnosis, a few months after disease onset.Case reportThe patient was a 66-year-old man with a history of  Crohn’s disease, but no other relevant medical antecedents and no relevant family history.He had been experiencing disabling and involuntary movements of  the right foot since July 2016, with no improvement on levetiracetam (dose limited to 1 g per day due to adverse events).He was referred to our department in October 2016. He described his symptoms as repetitive bursts of  movement in the right foot, each lasting only a few seconds and occurring up to 12 times per hour (during both night and day). There was no trigger. He reported the occurrence of  a strange feeling in his foot a few seconds before the movement began in some, but not all seizures. These movements were limited to his right foot. He reported no other symptoms. We observed rapid dystonic jerks Columbia University LibrariesFreely available onlineTremor and Other Hyperkinetic Movementshttp://www.tremorjournal.orgAbstractBackground: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a rare entity. Its typical features are seizures, faciobrachial dystonic seizures (FBDS), cogni-tive impairment, and personality changes.Case report: We report the case of  a 66-year-old man with an unusual presentation, consisting of  two types of  FBDS, one starting in the foot and the other consisting of  asynchronous myoclonic and dystonic jerks of  the face triggered by noise and chin stimulation. The patient displayed no personality changes or cogni-tive impairment.Discussion: LGI1 encephalitis is a heterogeneous disease. Many different forms of  FBDS may be observed, and these seizures can be the only symptom. This type of  encephalitis should be suspected in presenting very frequent episodic events with dystonic features, regardless of  the part of  the body affected.Keywords: Automimmune encephalitis, LGI1 encephalitis, LGI1 atypical presentation, dystonia, seizure-likeCitation: Rachdi A, Dupouy J, Beneteau M, Moreau MS, Courbon CB, Rascol O, et al. Leucine-rich glioma-inactivated 1 encephalitis: Broadening the sphere. Tremor Other Hyperkinet Mov. 2019; 9. doi: 10.7916/tohm.v0.663*To whom correspondence should be addressed. E-mail: ory.f@chu-toulouse.frEditor: Elan D. Louis, Yale University, USAReceived: April 9, 2019; Accepted: September 13, 2019; Published: October 9, 2019Copyright: © 2019 Rachdi et al. This is an open-access article distributed under the terms of  the Creative Commons Attribution–Noncommercial–No Derivatives License, which permits the user to copy, distribute, and transmit the work provided that the original authors and source are credited; that no commercial use is made of  the work; and that the work is not altered or transformed.Funding: None.Financial Disclosure: None.Conflicts of Interest: The authors report no conflict of  interest.Ethics Statement: All patients who appear on video have provided written informed consent; authorization for the videotaping and for publication of  the videotape was also obtained.Rachdi A, Dupouy J, Beneteau M, et al. Leucine-Rich Glioma-Inactivated 1 EncephalitisColumbia University LibrariesTremor and Other Hyperkinetic Movementshttp://www.tremorjournal.org 2beginning in the right foot that rapidly spread to the right hand and shoulder (but not the face) and lasted no more than a few seconds (Video 1). We also observed myoclonus and dystonic jerks of  the two sternocleidomastoid muscles that spread to the trapezius and neck mus-cles (Video 1), occurring asynchronously and independently of  the foot jerks. They were triggered by noise and chin stimulation and were not observed spontaneously in the absence of  a trigger. Interictal neurolog-ical examinations were otherwise normal.Magnetic resonance imaging revealed no abnormality. Repeated electroencephalography recordings showed no epileptiform discharges and no focal or generalized slowing, even during the ictus.Anti-LGI1 antibodies were detected in serum samples from the patient (titer: 1/7,500) but not in his cerebrospinal fluid.No neoplasia was detected on thoracic, abdominal, and pelvic com-puterized axial tomography or whole-body positron emission tomography.Treatment was initiated in February 2017 with a combination of  immunoglobulins (0.4 mg/kg per month) and steroids (methylpredniso-lone hemisuccinate, 1 g/day i.v., for 5 days, once monthly). By the fourth month of  treatment (June 2017), the symptoms had completely resolved and the anti-LGI1 antibodies were undetectable. After 6 months, steroid treatment was stopped due to adverse events ( recurrent unsightly facial mycosis and marked diabetes mellitus), and the patient was switched to immunoglobulins (same dose as during the previous 6 months) and cyclophosphamide (1 g i.v. per month). This treatment was maintained for the next 6 months. The patient remained symptom-free until the end of  this 12-month treatment period, after which treatment was stopped and replaced by medical surveillance.Discussion FBDS generally consist of  very brief  recurrent posturing of  the arm and ipsilateral hemiface. They are one of  the hallmarks of  LGI1 encephalitis, together with amnesia, seizures, and personality changes.1,2 Atypical FBDS have been described before, affecting the arm, face, and leg (in descending order of  frequency).2–5 Here, we report a patient with two unusual presentations of  FBDS.Some of  the dystonic jerks of  the right foot spread to the upper limb, but the patient only perceived and complained of  the foot move-ment. The patient said that the foot movements were highly disabling because of  their high frequency (up to 200 events on some days, as previously described2,3), causing him anxiety about the likelihood of  an attack and leading to him increasingly remaining in a chair or his bed during the daytime when the number of  FBDS increased. This may explain the absence of  serious falls, which have been reported in other patients,2 despite the high frequency of  crises in our patient. Another explanation for the lack of  falls is the “strange feeling” just before the attacks reported by the patient. Such manifestations have been described before as a sensory aura, and are sometimes difficult for the patient to describe and identify.2,4,5The myoclonic and dystonic facial manifestations were trigged by noise and skin contact. Other triggers, such as rapid movement and high levels of  emotion, have also been described2,3 and should be investigated during the clinical examination. We considered these movements to be atypical FBDS, as they were brief, like his other FBDS, without paroxysmal changes on Electroencephalogram (EEG). However, FBDS are considered to be a borderline manifes-tation between movement disorders and seizures, and their origin therefore remains a matter of  debate.5This patient was atypical in having FBDS as his only symptom. The number of  FBDS increased over time, and treatment initiation was delayed for 7 months by late diagnosis, but the patient’s neuropsycholog-ical test results remained completely normal. Cognitive dysfunction is another hallmark of  LGI1 encephalitis that may occur at any time during its course, although it is generally preceded by FBDS.2–4,6 The absence of  cognitive impairment in this patient may reflect the success of  the treatment in stopping FBDS, as it has been shown that the control of  FBDS can prevent cognitive dysfunction.3,7LGI1 encephalitis can be difficult to diagnose due to the presence of  atypical clinical features or because normal results are obtained for par-aclinical examinations. In our case, cerebral Magnetic Resonance Imaging (MRI) results were normal, as in up to 50% of  the cases described in a recent review.2We found no neoplasm, consistent with reported results, as 90% of  the patients included in published reviews were free of  tumors.2 Our patient had Crohn’s disease (which had been stable for years). The pos-sible link between these two diseases is unclear.Anti-LGI1 antibodies were detected in the patient’s serum, but not in his cerebrospinal fluid, consistent with the greater sensitivity of  detection for these antibodies in serum than in the Cerebro spinal fluid (CSF) (for a review, see Binks et al.2). However, high levels of  anti-LGI1 antibody in the cerebrospinal fluid may be predicted of  a worse neurological.8The atypical presentation in our patient delayed diagnosis, resulting in treatment initiation about 7 months after symptom onset. Treatment for LGI1 encephalitis should be initiated as soon as possible, to prevent [AQ1]Video 1. (A) Showing the Patient during Video-EEG. The patient experi-ences local dystonia of  the right foot (seconds 13--19) with no change in the EEG trace. Brief  dystonic posturing of  the right hand and forearm (see seconds 14–15) was also observed. (B) Another FBDS Occurring in an Asynchronous and Independent Manner, with Myoclonic and Dystonic Jerks of  the Face, Triggered by Noise and Chin Stimulation.Rachdi A, Dupouy J, Beneteau M, et al. Leucine-Rich Glioma-Inactivated 1 EncephalitisColumbia University LibrariesTremor and Other Hyperkinetic Movementshttp://www.tremorjournal.org 3cognitive decline, and possibly, to alter the clinical course of  the dis-ease.3,7 Steroid treatment in this patient was halted due to severe adverse events, which made a progressive decrease in steroid dose impossible. We chose a specific treatment regimen of  immunoglobulins and cyclo-phosphamide to prevent relapse2 and because too few data were avail-able for evidence-based selection of  the best treatment option.ConclusionLGI1 encephalitis is rare and has a highly variable presentation. The recognition of  FDBS is a key element for diagnosis, but LGI1 encephalitis must be diagnosed on whatever unilateral and focal fea-tures are observed.The time between FDBS onset and treatment initiation, and the presence of  cognitive decline, are two major prognostic factors. Neither MRI nor EEG can rule out this diagnosis, and treatment is based on immunotherapy.References1. Balint B, Vincent A, Meinck H-M, Irani SR, Bhatia KP. Movement disor-ders with neuronal antibodies: syndromic approach, genetic parallels and patho-physiology. Brain 2018;141(1):13–36. doi: 10.1093/brain/awx1892. Binks SNM, Klein CJ, Waters P, Pittock SJ, Irani SR. LGI1, CASPR2 and related antibodies: a molecular evolution of  the phenotypes. J Neurol Neurosurg Psychiatry 2018;89(5):526–534. doi: 10.1136/jnnp-2017-3157203. Irani SR, Michell AW, Lang B, Pettingill P, Waters P, Johnson MR, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol 2011;69(5):892–900. doi: 10.1002/ana.223074. Irani SR, Stagg CJ, Schott JM, Rosenthal CR, Schneider SA, Pettingill P, et al. Faciobrachial dystonic seizures: the influence of  immunotherapy on seizure control and prevention of  cognitive impairment in a broadening phenotype. Brain 2013;136(Pt 10):3151–3162. doi: 10.1093/brain/awt2125. Damato V, Balint B, Kienzler AK, Irani SR. The clinical features, underly-ing immunology, and treatment of  autoantibody-mediated movement disorders. Mov Disord 2018;33(9):1376–1389. doi: 10.1002/mds.27446. [Epub 2018 Sep 14].6. Gadoth A, Pittock SJ, Dubey D, McKeon A, Britton JW, Schmeling JE, et al. Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients. Ann Neurol 2017 Jul;82(1):79–92. doi: 10.1002/ana.249797. Thompson J, Bi M, Murchison AG, Makuch M, Bien CG, Chu K, et al. The importance of  early immunotherapy in patients with faciobrachial dys-tonic seizures. Brain 2018;141(2):348–356. doi: 10.1093/brain/awx3238. Gadoth A, Zekeridou A, Klein CJ, Thoreson CJ, Majed M, Dubey D, et al. Elevated LGI1-IgG CSF index predicts worse neurological outcome. Ann Clin Transl Neurol 2018;5(5):646–650. doi: 10.1002/acn3.561

Leucine-Rich Glioma-Inactivated 1 Encephalitis: Broadening the Sphere

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Leucine-Rich Glioma-Inactivated 1 Encephalitis: Broadening the Sphere

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