Esme Ekizoglu

Investigation of neuronal autoantibodies in two different focal epilepsy syndromes

Neuronal antibodies have been identified in patients with seizures as the main or sole symptom. Our aim was to investigate the prevalence of these autoantibodies in patients with focal epilepsy of unknown cause (FEoUC) and in the group having mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS).

Long‐term MRI findings in neuromyelitis optica: seropositive versus seronegative patients

Neuromyelitis optica (NMO) is a severe demyelinating inflammatory disorder associated with serum antibodies against aquaporin 4 (AQP4‐Ab). A significant number of patients with NMO remain seronegative over time. Long‐term observational magnetic resonance imaging (MRI) studies of the CNS in patients with NMO are rare or of limited duration. The objective of this study is to determine long‐term MRI characteristics of seropositive and seronegative patients, and assess possible overlap with multiple sclerosis (MS).

The analysis of allodynia in patients with idiopathic intracranial hypertension.

Objectives: Allodynia is frequently associated with migraine and other primary headaches. Our aim was to investigate the presence of allodynia and related features in idiopathic intracranial hypertension (IIH), which is a disabling secondary headache disorder. Methods: We included 46 IIH patients and analyzed their clinical and laboratory findings retrospectively. Allodynia was assessed using the validated 12-item allodynia symptom checklist (ASC-12), in addition to examining pressure (with von Frey filaments) and brush allodynia. Results: Allodynia was detected in 23 (50%) of IIH patients with ASC-12 and/or instrumental testing. The most commonly reported location was unilateral V1 distribution. The allodynic symptom profile was similar but milder when compared to 143 migraineurs with ASC-12. Only the aggravation of headache with physical activity emerged as a significant variable associated with allodynia in IIH. Among allodynic patients, only eight had previous migraine diagnosis. After onset of IIH, 20 patients reported migraine-like headache, while only three reported non-migrainous headache. In contrast, 13 of 23 non-allodynic IIH patients had non-migrainous headache features (p = 0.0045). Conclusion: Half of the IIH patients reported allodynia, and these allodynic patients had mostly migraine-like headache profiles. Our study suggested that IIH may trigger some common mechanisms with migraine in pain pathways causing allodynia.

Are There Any Specific EEG Findings in Autoimmune Epilepsies

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.

Glycine receptor and myelin oligodendrocyte glycoprotein antibodies in Turkish patients with neuromyelitis optica.

BACKGROUND Seronegative NMO is highly prevalent in non-Western countries implying the presence of as yet unknown antibodies (Ab). We investigated potential novel Ab in aquaporin-4 Ab (AQP-4-Ab) positive and negative NMO patients. METHODS Sera of 20 NMO patients were examined for AQP-4, myelin oligodendrocyte glycoprotein (MOG) and glycine receptor (GlyR) Ab by cell-based assays. RESULTS AQP-4-Ab was identified in 10 NMO patients, MOG-Ab was detected only in one AQP-4-Ab positive patient and GlyR-Ab was detected in two AQP-4-Ab negative patients. GlyR-Ab positive patients displayed simultaneous optic neuritis and transverse myelitis attacks and relatively low disability, whereas MOG and AQP-4-Ab double positive patient had a significantly increased disability. CONCLUSION This study showed for the first time the presence of GlyR-Ab in Turkish NMO patients. In contrast with previous reports, MOG Ab does not appear to be a distinctive marker for Turkish AQP-4-Ab negative NMO patients.

Aquaporin-4 antibodies are not present in patients with idiopathic intracranial hypertension

Objectives: We aimed to investigate anti-aquaporin-4 (AQP-4) water channel antibodies, affecting cerebrospinal fluid (CSF) secretion and absorption, in idiopathic intracranial hypertension (IIH) patients. Methods: Patients fulfilling the modified Dandy’s diagnostic criteria for IIH were included and their clinical features and CSF findings were reviewed. Their serum samples and control groups were investigated by immunofluorescence and a cell-based assay for anti-AQP-4 antibodies and by immunohistochemistry for IgG binding patterns. Results: Twenty-nine patients diagnosed with IIH were investigated. We could not detect any anti-AQP-4 antibodies in our series. However, we identified different serum IgG binding patterns in 11 IIH patients. Conclusion: There is only one report investigating the anti-AQP4 antibodies in IIH. Our study with a larger sample confirmed the results of this report and indicated that AQP4 antibodies did not have a primary role in IIH pathogenesis, but provided some support for the contribution of inflammatory mechanisms in IIH.

Oligoclonal bands and increased cytokine levels in idiopathic intracranial hypertension.

Objectives The pathogenesis of idiopathic intracranial hypertension (IIH) is currently unknown and there are speculations about the contribution of some immunologic factors. The aim of this study is to investigate the presence of oligoclonal bands (OCBs) and cerebrospinal fluid (CSF) and/or serum cytokine levels in patients with IIH. Methods Patients fulfilling revised diagnostic criteria for IIH were included. Their demographic, clinical, ophthalmologic and laboratory features were examined. Serum and CSF samples were detected by isoelectric focusing and immunoblotting for OCBs. The samples of IIH patients and control groups were investigated by ELISA for cytokine levels. Results We detected OCBs in eight (30.77%) patients diagnosed with IIH. There were no other obvious clinical and laboratory differences of IIH profiles between the patients with and without OCBs, but frequency of vision loss was significantly higher in the group with OCBs in comparison to OCB negatives (p = 0.038). Patients with IIH had highly elevated TNF-α, IFN-γ, IL-4, IL-10, IL-12, IL-17 in their sera compared to patients with multiple sclerosis (MS) and healthy controls. Furthermore, all cytokines except TNF-α in the CSF were found significantly higher in IIH patients compared to MS controls. Conclusion The presence of OCBs and elevated cytokine levels in IIH patients may support an immunologic background in the pathophysiological pathway of this disorder.

Neuronal autoantibodies in mesial temporal lobe epilepsy with hippocampal sclerosis

Objective Our aim was to investigate the prevalence of neuronal autoantibodies (NAbs) in a large consecutive series with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to elucidate the clinical and laboratory clues for detection of NAbs in this prototype of frequent, drug-resistant epilepsy syndrome. Methods Consecutive patients diagnosed with MTLE fulfilling the MRI criteria for HS were enrolled. The sera of patients and various control groups (80 subjects) were tested for eight NAbs after ethical approval and signed consents. Brain tissues obtained from surgical specimens were also investigated by immunohistochemical analysis for the presence of inflammatory infiltrates. The features of seropositive versus seronegative groups were compared and binary logistic regression analysis was performed to explore the differentiating variables. Results We found antibodies against antigens, contactin-associated protein-like 2 in 11 patients, uncharacterised voltage-gated potassium channel (VGKC)-complex antigens in four patients, glycine receptor (GLY-R) in 5 patients, N-methyl-d-aspartate receptor in 4 patients and γ-aminobutyric acid receptor A in 1 patient of 111 patients with MTLE-HS and none of the control subjects. The history of status epilepticus, diagnosis of psychosis and positron emission tomography or single-photon emission CT findings in temporal plus extratemporal regions were found significantly more frequently in the seropositive group. Binary logistic regression analysis disclosed that status epilepticus, psychosis and cognitive dysfunction were statistically significant variables to differentiate between the VGKC-complex subgroup versus seronegative group. Conclusions This first systematic screening study of various NAbs showed 22.5% seropositivity belonging mostly to VGKC-complex antibodies in a large consecutive series of patients with MTLE-HS. Our results indicated a VGKC-complex autoimmunity-related subgroup in the syndrome of MTLE-HS.

Characterization of Migraineurs Having Allodynia: Results of a Large Population-based Study.

Objective:Allodynia reflects the clinical correlate of central sensitization, but it is usually neglected in clinical headache management. We aimed to report the prevalence and previously unnoticed associations of allodynia in migraineurs by a nationwide face-to-face questionnaire-based study by physicians. Methods:A total of 5323 households were examined for headache according to the diagnostic criteria of International Classification of Headache Disorders-II. Detailed headache features, premonitory signs, demographics, socio-economic status, and hormonal status of female individuals were analyzed with regard to the presence of allodynia in patients with definite migraine. Results:Allodynia was present in 61.1% of migraineurs in the general population of Turkey. The duration and severity of attacks (P<0.0001), photophobia (P=0.001), phonophobia, and also osmophobia (P<0.0001), as well as premonitory signs (P=0.018), showed significant associations with allodynia. Migraineurs with aura or family history of migraine more often reported allodynia in comparison with those without (P=0.001 and 0.028, respectively). Allodynic migraineurs had a higher rate of physician consults and high levels on the Migraine Disability Assessment questionnaire, reflecting increased burden of headache. Furthermore, migraineurs with allodynia had high probability of attacks close to menses. Migraine improved during pregnancy, but it worsened after menopause or during oral contraceptive use in individuals experiencing allodynia when compared with those without allodynia. Discussion:The duration, severity, and disability of migraine attacks, photophobia, phonophobia, and osmophobia, as well as premonitory signs, showed significant associations with allodynia in the general population. Moreover, migraineurs with aura or family history of migraine more often reported allodynia, and allodynic migraneurs were more sensitive to hormonal changes. Allodynia, which seems to indicate higher tendency to central sensitization, should be implemented in daily headache practice to predict the prognosis and high levels of migraineous involvement.

Sleep characteristics of patients with epilepsy with pure sleep-related seizures.

OBJECTIVE Our aim was to investigate the clinical features and sleep characteristics of patients with pure sleep-related seizures. METHODS Patients with pure sleep epilepsy were prospectively enrolled and their clinical, EEG, and MRI findings investigated. The Medical Outcomes Study Sleep Scale (MOS-SS) was administered after receiving consent. RESULTS Thirty-nine of 1401 consecutive patients (2.7%) with pure sleep-related seizures were included. Of these, 30 (76.9%) had epilepsy of unknown cause and 7 had epilepsy with known structural etiologies. Twenty-seven patients reported less than one seizure per month and 19 had been seizure free for at least 1 year. Thirty-four patients participated in our MOS-SS study. Comparison of sleep problems between those with epilepsy and healthy controls and between the subgroups with frequent and rare seizures did not reveal significant differences. CONCLUSION Patients with pure sleep seizures had mostly undetermined etiology usually with a good prognosis, and this rare condition did not seem to affect their sleep quality.