Non-Paraneoplastic Limbic Encephalitis Characterized by Mesio-Temporal Seizures and Extratemporal Lesions: a Case Report

Seizure 19 (2010) 446–449

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Case report Non-paraneoplastic limbic encephalitis characterized by mesio-temporal seizures and extratemporal lesions: A case report

Vittoria Cianci a,b, Angelo Labate a, Pierluigi Lanza d, Angela Vincent e, Antonio Gambardella a,d, Damiano Branca c, Luciano Arcudi c, Umberto Aguglia a,b,* a Institute of Neurology, Magna Græcia University of Catanzaro, Italy b Magna Græcia University of Catanzaro; Regional Epilepsy Center, Italy c Neurological Unit, ‘‘Riuniti’’ Hospital of Reggio Calabria, Italy d National Research Council, Piano Lago–Mangone, Cosenza, Italy e Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Department of Clinical Neurology, England, United Kingdom

ARTICLE INFO ABSTRACT

Article history: Limbic encephalitis (LE) can be either paraneoplastic or a non-paraneoplastic autoimmune disorder. Received 12 December 2009 Magnetic resonance imaging (MRI) of the brain on T2-weighted ﬂuid-attenuated inversion recovery Received in revised form 21 May 2010 (FLAIR) classically shows hyperintensities of the temporal structures, but multifocal involvement of Accepted 4 June 2010 extratemporal cortex has also been described in paraneoplastic LE. Here we describe a 27-year-old woman whose idiopathic autoimmune (glutamic acid decarboxylase-antibody positive) LE debuted with Keywords: multiple daily mesio-temporal seizures, amnesia and multifocal extratemporal cortical MRI Antibodies abnormalities. Mesio-temporal MRI signal increase was found after 20 days. This case report highlights Epilepsy that early diagnosis of non-paraneoplastic LE may be considered in patients with multiple daily mesio- GAD Limbic encephalitis temporal seizures and amnesia even in the absence of early typical MRI abnormalities. Magnetic resonance imaging ß 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. Seizures

1. Introduction 2. Case report

It is now accepted that limbic encephalitis (LE) can be A 27-year-old woman with no family or personal history of paraneoplastic or non-paraneoplastic.1–3 In non-paraneoplastic epilepsy or febrile convulsions presented at the emergency room cases, high serum levels of voltage-gated potassium channels because of daily episodes of funny feelings four days after a febrile (VGKC) antibodies (Abs)2,3 have been found, as well as Abs directed episode. At admission to neurology department, she was against glutamic acid decarboxylase (GAD),4 N-methyl-D-aspar- diagnosed of mesio-temporal lobe epilepsy with multiple daily tate (NMDA) receptor/channel or to unknown antigens.5 The seizures. In the past history, she had depression, anxiety treated typical clinical presentation of idiopathic LE is a subacute onset of with antidepressants, and autoimmune Hashimoto’s thyroiditis confusion, anterograde amnesia, temporal lobe seizures and diagnosed at the age of 24 and treated for 11 months with behavioral changes. Magnetic resonance imaging (MRI) of the corticosteroids that were stopped 18 months before. Her interictal brain on T2-weighted fluid-attenuated inversion recovery (FLAIR) neurological examination was normal. The neuropsychological shows hyperintensities with swelling usually restricted to the examination included Raven’s coloured progressive matrices mesio-temporal cortex, with late atrophy and occasional involve- [score = 23.5, normal value (n.v.) > 17.5], immediate and delayed ment of other temporal structures.6,7 Extratemporal cortical recall of a short story (score = 4, n.v. > 6.5), thirty paired word involvement has been reported only in patients with paraneo- associates (score = 4, n.v. >6.5), semantic verbal fluency test plastic LE.8–11 Here we describe a young woman whose idiopathic (score = 36, n.v. > 17), phonemic verbal fluency test (score = 31, autoimmune LE debuted with mesio-temporal seizures associated n.v. > 25), and revealed severe impairment of recent memory, with with multifocal cortical extratemporal abnormalities. preservation of language functions. The interictal EEG showed spike-waves over the right temporal lobe (Fig. 1a). Ictal video-EEG monitoring showed seizure pattern consisting of temporo-parietal, rhythmic theta waves followed by epigastric aura (Fig. 1b), and * Corresponding author at: Centro Regionale Epilessie, Presidio Riuniti, Via Melacrino, 89100, Reggio Cal., Italy. Tel.: +39 333 3167327; fax: +39 0965 397973. spiking activity and diffuse fast rhythms associated with fear, E-mail address: [email protected] (U. Aguglia). flushing, diaphoresis and de´ja`-vu without loss of consciousness or

1059-1311/$ – see front matter ß 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.seizure.2010.06.002 [(Fig._1)TD$IG] V. Cianci et al. / Seizure 19 (2010) 446–449 447

Fig. 1. EEG at admission to neurology department; (a) interictal EEG. Note spike-waves over the right temporal lobe; (b)–(d) ictal EEG. Note disappearance of the alpha activity and presence of rhythmic theta waves on leads P4, T4 and T6. Epigastric aura occurred six sec after onset (b). Spikes and spiking activity on leads T6, P4, F8 and T4 and diffuse fast (13–16 Hz) rhythms were associated with fear, flushing, diaphoresis and de´ja`-vu (c) and (d); (e) end of the seizure (40 s after (d)). There was no loss of consciousness during the seizure. language disorders (Fig. 1c–e). Temporo-spatial disorientation and showed the presence of oligoclonal bands, with normal protein sometimes amnesia followed the seizures. Visual and somatosen- and cellular content. No serum antibodies against onconeural sory evoked potentials were normal. Routine laboratory analyses antigens were found. PCR amplification for herpes simplex virus were normal (including glucose), but the sodium level was low (HSV) on CSF, serum antibodies to herpes simplex virus (HSV), 126 mEq/L (n.v. 135–145). Cerebrospinal fluid (CSF) analysis human herpes virus (HHV)-6 and HHV-7, extensive serum tests for 448 V. Cianci et al. / Seizure 19 (2010) 446–449 viral, bacterial and fungal infections, neoplastic serum markers brain, did not show any abnormality. On admission, 2 days after (Carcinoembryonic antigen, alpha-fetoprotein, Ca125, Ca19-9, the onset of illness, T2, FLAIR, and diffusion-weighted brain MRI Ca15-3), Anti-Nuclear-Abs, antibodies to Extractable-Nuclear- sequences showed two small hyperintensity areas localized in the Antigen, cytoplasmic-Antineutrophil Cytoplasmic-Abs (cANCA), parietal cortex of the right hemisphere and in the fronto-basal perinuclear-ANCA, anti-transglutaminase-Abs and anti-gliadin- cortex of the left hemisphere, with no contrast enhancement. Abs were negative or normal. At that time, no serum reactivity to Surprisingly, no abnormalities were observed in the temporal VGKC-Abs or to the NR1/NR2 heteromers of the NMDA receptor/ lobes (Fig. 2a–c) at this time, but a second MRI performed 20 days channel was detected (A.V.), whereas a radioimmunoprecipitation later showed typical bilateral swelling with hyperintensity (with assay evaluation of stored serum and CSF collected at entry no contrast enhancement) of the mesial temporal lobes bilaterally, demonstrated very high levels of anti-GAD-Abs in the serum but more evident on the right side, as well as persistence of the (6000 U/ml normal value < 1.0 U/ml) and in CSF (120 U/ml, extratemporal lesions (Fig. 2d–f). The patient was treated with normal value: < 1 U/ml). The anti-GAD intrathecal synthesis index anti-epileptic medication (topiramate 200 mg/day) and i.v. meth- [CSF anti-GAD IgG value/serum anti-GAD value]/[CSF albumin/ ylprednisolone (1 g/day for five consecutive days). One week after serum albumin], (positive value > 1) was positive (value: 7.7). steroid treatment, the seizures were reduced in frequency and Thyroid hormones were also normal, while high serum titer of both duration, the interictal EEG was normal and MRI showed only the antithyroid microsomal (424 IU/ml, n.v. < 50) and antithyroid persistence of hyperintensity over the right mesial temporal lobe peroxidase (3334 IU/ml: n.v. < 60) antibodies were at lower levels (Fig. 2g–i). The patient was discharged with anticonvulsant than 30 months previously (anti-microsomal-Abs: 800 IU/ml; therapy only. However, at follow-up (1, 2 and 3 months after [(Fig._2)TD$IG]anti-peroxidase-Abs: 4585 IU/ml). Whole-body CT, including the end of immunotherapy) she still had severe impairment of the

Fig. 2. MRI (FLAIR-sequences). At entry (a)–(c): note two small intracortical lesions localized in the parietal cortex of the right hemisphere (10 mm: (a) and (b)) and in the fronto-basal cortex of the left hemisphere (6 mm: (c)). No abnormalities were observed in the temporal lobes. Twenty days after admission (d)–(f): persistence of the extratemporal cortical lesions (d) and (e) with bilateral hyperintensity and swelling of the mesial temporal lobes (more evident on the right side: (e) and (f). Seven days after immunotherapy (g)–(i) persistence of hyperintensity of the mesial temporal lobe on the right side and disappearance of the other lesions. V. Cianci et al. / Seizure 19 (2010) 446–449 449 recent memory and her temporal lobe seizures had become and multifocal extratemporal cortical abnormalities, in the resistant to anti-epileptic treatment, but she refused treatment absence of typical limbic lesions seen on MRI at onset of disease. with i.v. immunoglobulins or oral steroids. Six months after onset, Besides in patients with LE with classic MRI features, GAD-Abs a repeated MRI was unchanged (showing only right temporal lobe should also be assayed in patients with subacute onset of amnesic signal abnormality, without hippocampal atrophy) and whole- syndrome, temporomesial seizures and extratemporal MRI abnor- body PET scan was normal. Treatment with oral prednisone malities. (50 mg/day) was then accepted. Six months after onset of oral prednisone, neurological and psychometric evaluations were unchanged. References

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