Journal of the Neurological Sciences 347 (2014) 404–405

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Letter to the Editor Faciobrachial dystonic seizures and antibodies to Lgi1 in a 92-year-old patient: A case report

Keywords: Faciobrachial dystonic seizures Leucine-rich glioma inactivated-1 Antibodies Autoimmune encephalitis Intravenous immunoglobulins

Dear sir, Faciobrachial dystonic seizures (FBDS) have recently been characterized as a distinctive type of seizures, which frequently precede the onset of limbic encephalitis and are associated with antibodies to the leucine-rich glioma inactivated-1 (Lgi1) protein [1]. We here report on a novel patient with FBDS and antibodies to Lgi1, who had a remarkably old age at first manifestation of the disease, but still showed a complete remission of FBDS following immunotherapy with intravenous immunoglobulins (IVIG). The patient provided written informed consent for publication of this report. A 92-year-old woman in previously excellent physical and mental health developed short, jerky, unilateral, involuntary movements predominantly of the left, but occasionally also of the right arm and face in January 2012. The episodes lasted about a second, occurred several times per day, and were occasionally associated with involuntary vocalizations. There were no prodromal symptoms and no loss of consciousness, and the patient had no cognitive decline, memory impairment or behavioral changes. Except for emotional stress, she noted no particular triggers. Over a few weeks, the episodes increased in frequency (up to 100/day) and led to a fall, resulting in a right humeral fracture necessitating surgery. She was subsequently started on pregabalin, which had no effect on the frequency of her attacks and was discontinued few weeks later. Six months after disease onset, another fall resulted in a fracture of the left lesser trochanter, which again had to be treated surgically. In July 2012, a thorough neurological examination as well as somatosensory and motor evoked potentials were normal. Likewise, electroencephalography demonstrated normal alpha activity without focal abnormalities or epileptiform discharges. Her mini mental state examination score was 29 out of 30. A cerebral MRI was unremarkable except for mild generalized atrophy and microangiopathic leukoencephalopathy. Whole body fluorodeoxyglucose-positron emission tomography (FDG-PET) showed no neoplasia, but revealed prominent bilateral hypermetabolism in the striata (Fig. 1). Antibody testing on Lgi1transfected HEK293 cells (Euroimmun, Lübeck, Germany) demonstrated IgG antibodies to Lgi1 with a titer of 1:320 in the patient's serum. Cerebrospinal fluid was not available for antibody testing. A large

http://dx.doi.org/10.1016/j.jns.2014.10.026 0022-510X/© 2014 Elsevier B.V. All rights reserved.

panel of other serum autoantibodies (antinuclear antibodies, antineutrophil cytoplasmic antibodies, antibodies to extractable nuclear antigens, Ri, Yo, Hu, Tr, MAG, Myelin, Ma/Ta, GAD, amphiphysin, AQP4, NMDA-R, AMPA-R, GABAB-R, CV2, PNMA2, CASPR2, and glycine receptor) was negative. She had no hyponatremia. A diagnosis of Lgi1-antibody-associated FBDS was made and the patient was treated with IVIG (30 g/day for one day and 40 g/day for 3 days). On a followup examination in October 2012, the patient reported a marked reduction in both FBDS frequency and intensity, which was paralleled by a decreased Lgi1 serum IgG titer (1:10). The attacks were now confined to the left side of the face and the left hand. Intravenous immunoglobulin treatment was repeated in October 2012 (40 g/day for 3 days) and in June 2013 (40 g/day for 2 days) and was associated with a further reduction and eventually complete remission of FBDS. The patient currently (August 2014) has no FBDS and is expecting her 95th birthday. The clinical and serological findings of our patient are highly reminiscent of the patients with FBDS reported in the original series [1,2], strongly suggesting that she suffered from Lgi1-antibody-associated FBDS. This is further supported by bilateral striatal hypermetabolism on FDG-PET, which was previously observed in patients with antibodies to Lgi1 [1,3,4]. Nevertheless, to the best of our knowledge, only one patient with a similarly old age at first manifestation of Lgi1-antibodyassociated FBDS has been reported so far [5]. Together, these cases indicate that Lgi1 autoimmunity can manifest also at a very advanced age. Clinicians should thus be aware of the broad age range at first manifestation of Lgi1-associated FBDS and Lgi1 antibody testing should be considered in elderly patients with jerky movements or unexplained falls, which may otherwise be mistaken as neurodegenerative or unspecific age-related phenomena. While FBDS are frequently associated with falls [1,5], likely because of her old age, two falls in our patient resulted in fractures necessitating surgery. Because of this significant morbidity and because FBDS can herald limbic encephalitis immunotherapy appeared warranted. Given the advanced age of our patient, she was treated with IVIG rather than with corticosteroids, azathioprine, rituximab, or plasma exchange [1,5–7]. This was associated with cessation of FBDS and no further falls and fractures after a follow-up of currently more than 2.5 years. It should be noted that the IVIG treatment effect appeared to have occurred less rapid than that described for corticosteroids [5] and also a spontaneous remission cannot be excluded. However, the reduction of FBDS clearly coincided with the start of IVIG therapy, suggesting that IVIG might be a possible treatment approach in elderly patients with FBDS, especially regarding the frequent comorbidities (e.g. osteoporosis, diabetes) limiting the use of corticosteroids in this patient group. Still, in the absence of contraindications, corticosteroid therapy represents an important treatment option also in elderly patients with FBDS [5]. In conclusion, autoimmune encephalitides may manifest at a very old age and must be taken into account in the differential diagnosis of movement disorders or neuropsychiatric abnormalities in an age group where untreatable neurodegenerative diseases are often

Letter to the Editor

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Fig. 1. (A) Coronal section of cerebral fluorodeoxyglucose-positron emission tomography (FDG-PET) demonstrating bilateral hypermetabolism in the striata (arrows). The image was obtained shortly before the first IVIG treatment. (B) Coronal fluid attenuated inversion recovery MRI image shows mild generalized atrophy, microangiopathic leukoencephalopathy, but no abnormalities in the basal ganglia.

suspected in the first place. Since immunotherapy may be associated with marked improvement of symptoms even in patients with a very advanced age, correct diagnosis of autoimmune encephalitides is important and immunotherapy, including IVIG, should be considered also in this age group.

Conflict of interest The authors declare that they have no conflict of interest. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References [1] Irani SR, Michell AW, Lang B, Pettingill P, Waters P, Johnson MR, et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol May 2011; 69(5):892–900. [2] Irani SR, Buckley C, Vincent A, Cockerell OC, Rudge P, Johnson MR, et al. Immunotherapy-responsive seizure-like episodes with potassium channel antibodies. Neurology Nov 11 2008;71(20):1647–8. [3] Wegner F, Wilke F, Raab P, Tayeb SB, Boeck AL, Haense C, et al. Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography. BMC Neurol 2014;14:136. [4] Boesebeck F, Schwarz O, Dohmen B, Graef U, Vestring T, Kramme C, et al. Faciobrachial dystonic seizures arise from cortico-subcortical abnormal brain areas. J Neurol Jun 2013;260(6):1684–6. [5] 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 Oct 2013;136(Pt 10):3151–62. [6] Irani SR, Gelfand JM, Bettcher BM, Singhal NS, Geschwind MD. Effect of rituximab in patients with leucine-rich, glioma-inactivated 1 antibody-associated encephalopathy. JAMA Neurol Jul 1 2014;71(7):896–900.

[7] Shin YW, Lee ST, Shin JW, Moon J, Lim JA, Byun JI, et al. VGKC-complex/LGI1-antibody encephalitis: clinical manifestations and response to immunotherapy. J Neuroimmunol Dec 15 2013;265(1–2):75–81.

Pawel Fidzinski Department of Neurology, Charité — Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany Sven Jarius Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany Christian Gaebler Department of Neurology, Charité — Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany Friedrich Boegner Roland Nohr Department of Neurology, Theodor-Wenzel-Werk Berlin, Potsdamer Chaussee 69, 14129 Berlin, Germany Klemens Ruprecht Department of Neurology, Charité — Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany Corresponding author at: Department of Neurology, Charité — Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Tel.: +49 30 450 560 374; fax: +49 30 450 560 922. E-mail address: [email protected]. 7 September 2014

Faciobrachial dystonic seizures and antibodies to Lgi1 in a 92-year-old patient: a case report.

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