The purpose of this study was to evaluate systematically shape and positioning of the hippocampal formation (HF) in patients with partial epilepsy related to malformations of cortical development (MCD) and those with temporal lobe epilepsy (TLE). We studied 76 patients with MCD, including focal cortical dysplasia (n = 29; lesions located outside the temporal lobe in all), heterotopia (lesions outside of the temporal lobe, n = 14; lesions extending into the temporal lobe, n = 16), polymicrogyria (bilateral perisylvian, n = 14; unilateral perisylvian, n = 3) and 30 patients with TLE (hippocampal atrophy, n = 15; normal hippocampal volumes, n = 15). Shape and positioning of the HF were evaluated using a set of eight predefined morphological characteristics. In addition, the degree of hippocampal vertical orientation and medial positioning were assessed quantitatively. Patients were compared with 50 healthy controls. At least three criteria describing abnormal HF shape and positioning were found in 5/50 (10%) healthy controls, 37/76 (49%) MCD and 13/30 (43%) TLE patients. An association with all criteria was found in MCD and TLE, but not in healthy controls. In MCD there was no association between the side of HF shape abnormalities and the side of the cortical malformation or the EEG focus. Likewise, in TLE, HF abnormalities were not related to the side of the EEG focus. In both MCD and TLE patients who had hippocampal atrophy, no association was found between the side of HF shape abnormalities and the side of atrophy. Abnormal HF shape and positioning are found in a similar proportion in MCD and TLE. In TLE, they may be a marker of a more extensive disorder of brain development and may participate in the development of this condition.

The clinical features and EEGs of 45 consecutive patients (40 adults and 5 children) who had periodic lateralized epileptiform discharges (PLEDs) were reviewed to determine the relationship between seizures and PLEDs. Focal encephalitis and ischemic stroke were the most frequent underlying processes for adult patients. All of the children, but only six of the adults, had long-lasting cerebral disorders whereas the remaining adults had acute or subacute illness. There were 38 patients (84.4%) experiencing a seizure disorder. Twenty-six of them had their first seizure during their acute illness, as the pattern of PLED was encountered. Eight cases had status epilepticus, and seven of them had epilepsia partialis continua. Nineteen patients had a recent seizure in the day when PLEDs were observed but not during EEG recording; 12 patients had their seizures within 10 days before the observation of PLED. PLEDs were grouped into three categories with respect to their extensions: lateralized to one hemisphere (n = 22), localized in one region (n = 17) and being prominent over one side with contralateral spread (n = 6). The last group was found to be more closely associated with frequent seizures or status epilepticus than the other two groups. Our results showed that PLEDs were highly correlated with recent seizures in the majority of the patients. These EEG findings may be considered as a manifestation of an increased neuronal excitability caused by different etiologies; but not an ictal pattern.

A small hippocampus was present in all types of MCD; however, the classic MRI characteristics of hippocampal sclerosis were often lacking. Abnormal enlargement of the hippocampus was associated with only diffuse MCD due to abnormal neuronal migration (lissencephaly-agyria-pachygyria and SLH).

This study evaluated the EEG findings of patients whose seizures were associated with a possible autoimmune etiology. Our aim was to find clues to distinguish patients with antineuronal antibodies (Ab) through EEG studies. We reviewed our database and identified antineuronal Ab positive epilepsy patients with or without autoimmune encephalitis. These patients had Abs to N-methyl-d-aspartate receptor (NMDAR) (n = 5), glycine receptor (GLY-R) (n = 5), contactin-associated protein-like 2 (CASPR-2) (n = 4), uncharacterized voltage-gated potassium channel complex (VGKC) antigens (n = 2), glutamic acid decarboxylase (GAD) (n = 2), Hu (n = 1), and amphiphysin (n = 1). The control group consisted of 21 seronegative epilepsy or encephalopathy patients with similar clinical features. EEG findings were compared between the groups in a blindfolded design. We did not find any significant difference in EEG findings between antineuronal Ab positive epilepsy patients and seronegative control group. It was remarkable that four seropositive but none of the seronegative patients presented with nonconvulsive status epilepticus (NCSE) or focal motor status epilepticus. Continuous theta and delta rhythms were observed in 5 (71%) seropositive patients with autoimmune encephalitis and 2 (25%) seronegative patients. Eight (40 %) seropositive patients showed a frontal intermittent rhythmic delta activity (FIRDA) pattern as opposed to 5 (24%) seronegative patients. Two patients with NMDAR Ab positivity showed rhythmic delta waves superimposed with beta frequency activity resembling "delta brush" pattern. EEG seems as a limited diagnostic tool in differentiating epilepsy and/or encephalopathy patients with a possible autoimmune etiology from those without. However, antineuronal Abs associated with encephalitis should be considered in the etiology of status epilepticus forms. A possible autoimmune etiology for seizures may be considered in the presence of continuous slow waves, FIRDA, and delta brush pattern in the EEG.

Aim. Rasmussen encephalitis is associated with severe seizures that are unresponsive to antiepileptic drugs, as well as immunosuppressants. Transcranial direct current stimulation (t‐DCS) is a non‐invasive and safe method tried mostly for focal epilepsies with different aetiologies. To date, there is only one published study with two case reports describing the effect of t‐DCS in Rasmussen encephalitis. Our aim was to investigate the effect of t‐DCS on seizures in Rasmussen encephalitis and to clarify its safety. Methods. Five patients (mean age: 19; three females), diagnosed with Rasmussen encephalitis were included in this study. Patients received first cathodal, then anodal (2 mA for 30 minutes on three consecutive days for non‐sham stimulations), and finally sham stimulation with two‐month intervals, respectively. Three patients received classic (DC) cathodal t‐DCS whereas two patients received cathodal stimulation with amplitude modulation at 12 Hz. Afterwards, all patients received anodal stimulation with amplitude modulation at 12 Hz. In the last part of the trial, sham stimulation (a 60‐second stimulation with gradually decreasing amplitude to zero in the last 15 seconds) was applied to three patients. Maximum current density was 571 mA/m2 using 70 mm × 50 mm wet sponge electrodes with 2‐mA maximum, current controlled stimulator, and maximum charge density was 1028 C/m2 for a 30‐minute stimulation period. Results. After cathodal stimulation, all but one patient had a greater than 50% decrease in seizure frequency. Two patients who received modulated cathodal t‐DCS had better results. The longest positive effect lasted for one month. A second trial with modulated anodal stimulation and a third with sham stimulation were not effective. No adverse effect was reported with all types of stimulations. Conclusion. Both classic and modulated cathodal t‐DCS may be suitable alternative methods for improving seizure outcome in Rasmussen encephalitis patients.

Objective: To describe a potential association between comorbid autoimmune disease and Rasmussen encephalitis (RE) and discuss potential insights into underlying RE pathogenesis. Methods:We report a case series of 4 patients with RE in whom a comorbid autoimmune disease was subsequently diagnosed and review the literature on possible common susceptibility factors.Results: In 4 patients who presented with typical clinical features of RE, a comorbid autoimmune disease was subsequently diagnosed: Hashimoto thyroiditis, ulcerative colitis, Crohn disease, and systemic lupus erythematosus. We discuss the possible common predisposing factors. Conclusions:The association of RE, a rare entity, with a comorbid autoimmune disease raises the possibility of shared mechanisms of susceptibility, including common immunogenetic and/or environmental risk factors. Neurology ® 2014;83:1049-1055 GLOSSARY a7nAChR 5 a7 nicotinic acetylcholine receptors; AID 5 autoimmune disease; ANA 5 antinuclear antibodies; CD 5 Crohn disease; GWAS 5 genome-wide association studies; HT 5 Hashimoto thyroiditis; Ig 5 immunoglobulin; IVIg 5 IV immunoglobulin; RE 5 Rasmussen encephalitis; SLE 5 systemic lupus erythematosus; T1D 5 type 1 diabetes; UC 5 ulcerative colitis.

Precipitation of spike and wave (SW) discharges in some epileptic patients by eye closure (EC) has rarely been reported. To disclose the clinical characteristics and classification of syndromes of epileptic patients with SW discharges induced by EC, we investigated 10 patients (1 M, 9 F) showing this peculiar EEG feature. The patients aged between 9-39 years (mean 20.6 +/- 9.058), underwent short-term (1-3.5 hr) video-EEG investigations in order to document the appearance of the SW discharges within 3 seconds of the act of EC, in at least two occasions. Clinical analysis showed that 5 female patients who had the syndrome of juvenile myoclonic epilepsy (JME) had a later onset of epilepsy (13-15 years) than the 3 patients (3 girls) with eyelid myoclonia with absences (EMA) (3-8 years of age at onset). The remaining 2 patients who were diagnosed as childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) according to the international classification, did not show photosensitivity on the video-EEG. All but one of the 5 JME patients had experienced myoclonic seizures in intermittent photic stimulation (IPS) at the time of EC, associated with multiple spike and wave discharges. Two of the 3 EMA patients exhibited typical absences with eyelid myoclonia during the act of EC. The high rate of family history of epilepsy in first degree relatives of our patients was an outstanding feature, which could have future implications in research of the genetic basis of epilepsy patients with ECS.

Aim. Rasmussen's encephalitis (RE) is a rare disease with unknown pathophysiology. To disclose whether anti‐neuronal autoimmunity participates in the aetiology of RE, various neuronal autoantibodies (NAAbs) were investigated in sera of patients with RE and controls. Methods. The study included five patients who fulfilled the RE diagnostic criteria (clinical, EEG, and MRI findings) as the patient group, and 50 multiple sclerosis patients and 50 healthy subjects as the control groups. Sera were evaluated for various NAAbs by radioimmunoassay or cell‐based assays. All sera were also screened for uncharacterized antibodies to neuronal cell surface or synapse antigens by indirect immunofluorescence using hippocampal cell cultures. Results. The mean age at onset of seizures was 8.3±3.4 years (range: 4–13.5) and mean follow‐up time was 11.2±5.4 years (range: 5–19). All patients had unihemispheric atrophy of the cerebral cortex and epilepsia partialis continua. Two of the patients had moderate cognitive impairment, while the others were severely affected, as shown by neuropsychological testing. NAAb positivity was not detected in any of the patients. Conclusion. Immune aetiology is thought to have a role in RE, but the responsible players have not yet been elucidated. Our extensive antibody screening in a small number of patients does not support the presence of antigen‐specific anti‐neuronal autoimmunity in RE pathophysiology.