Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up AppendixVan Sonderen et al.

Online supplemental material

Laboratory methods

Seizure and EEG description of two patients with LGI1 encephalitis

Table e-1. Description of CANTAB tests included in neuropsychological assessment

Figure e-1. Immunohistochemistry on rat brain

Figure e-2. Results of initial and serial MRI

Laboratory methods

LGI1 antibodies were detected with both commercially available cell-based immunofluorescence assay (CBA) according to the manufacturer’s instructions (Euroimmun, Lübeck, Germany) and immunohistochemistry (IHC). IHC was performed on rat brain,(1) and considered positive if it showed hippocampal staining typical for LGI1-antibodies (Suppl Figure 1). Tests were performed on both serum and cerebrospinal fluid (CSF) if available. Sera were tested for antibodies to the VGKC-complex by commercial radioimmunoassay (RIA; result >100 pM considered positive) according to the manufacturer’s instructions (DLD Diagnostika GmbH, Hamburg, Germany). Immunoblot assays were used to test for antibodies to onconeuronal antigens (CV2, Hu, Ma1, Ma2, Ri, Tr, Yo, amphiphysin) and CBA for Caspr2 and NMDA receptor antibodies (Ravo Diagnostika GmbH, Freiburg, Germany and Euroimmun, Lübeck, Germany, performed according to manufacturer’s instructions).

Seizure and EEG description of two patients with LGI1 encephalitis

Patient1presents with painful legs and hyperhidrosis. After six months paroxysmal symptoms started, consisting of faciobrachial dystonic seizures and focal seizures with dyscognitive and autonomic features, as described below. Progressive cognitive impairment evolved, followed by tonic-clonic seizures. Two different attacks occurred during 24-hours EEG:

-Up to seventy attacks lasting for several seconds with a tonic posture of the right hand, arm, neck and the right corner of the mouth. Patient is able to push the button to report these events. Ictal EEG recordings show no abnormalities besides muscle artifacts.

-Up to twenty episodes characterized by pupillarydilation, heavy breathing and an anxious facial expression. The patient reports nausea and an urge to vomit. Consciousness seems to be retained and after the attack patient immediately responds appropriately. During the attack, EEG shows theta or delta activity, followed by sharp waves and spike and wave complexes over the midfrontal and left frontal areas, with rapid recovery.

Patient 2 presents with mild behavioral problems. A few months later, memory declined and seizures started. Patient reports autonomic attacks lasting only seconds, occurring several times a day. These attacks consist of goose bumps and a shiver, sometimes accompanied by smelling a strange odor. Spouse described an early attack with dyscognitive features while the patient was driving a car. Patient was told to stop the car and they changed seats. After a few minutes, patient asked ‘how did I get in the passenger’s seat?’. Forty attacks similar occurred during 24-hours EEG registration:

-Attacks start with a shiver, sniffing and a pale face. Patient stops talking but is able to follow commands, without remember these afterwards. EEG started to become slow and irregular, followed by sharp waves and spike and wave complexes with a maximum over the frontal-temporal areas.

Table e-1. Description of CANTAB tests included in neuropsychological assessment
Test / Cognitive domain / Description
Graded naming task (GNT) / Verbal memory / Objects appear on the screen. Participants are instructed to name the object.
Delayed matching to sample (DMS) / Visual memory / A complex pattern appears on the screen. After a brief delay, four patterns appear. Participants must touch the pattern that matches the sample.
Pattern recognition memory (PRM) / Visual memory / Learning phase: several patterns appear, one at a time. Recognition phase: participants choose which of two patterns they have seen before
Spatial recognition memory (SRM)* / Visual memory / Learning phase: a white square is shown in various locations. Recognition phase: participants choose which of two boxes is in a location previously presenting a square.
Intra-extra dimensional set shift (IED)* / Executive function / Participants must first use feedback to learn a rule involving two dimensions. When feedback implies that the rule has changed, the participant must shift attention to the previously irrelevant dimension. Derived from the Wisconsin Card Sorting Test.
Spatial working memory (SWM) / Executive function / Participants search for blue tokens by touching colored boxes throughout the screen, without returning to a box where a blue token was previously found.
Spatial span (SSP) / Executive function / White squares on the screen briefly change color in a variable sequence. Participants must remember the sequence and touch squares in the same order, with growing sequence length throughout the test.
Matching to sample (MTS) / Attention / A test pattern is shown. Participants have to choose the matching pattern from a possible 8 patterns, measuring speed and accuracy.
Reaction time (RTI) / Attention / The participant must hold down a button until a yellow spot appears on the screen, and then touch the yellow spot.

CANTAB = Cambridge Neuropsychological Test Automated Battery

*Primary outcome measures

Reference List

(1) Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain 2005 Aug;128:1764-1777.