Psychogenic non-epileptic seizures (PNES) in the context of concurrent epilepsy – making the right diagnosis

Epilepsy is a risk factor for the development of psychogenic non-epileptic seizures (PNES) and comorbid epilepsy is recognized as a comorbidity in about 10–30% of patients with PNES. The combination of epileptic and nonepileptic seizures poses a particular diagnostic challenge. In patients with epilepsy, additional PNES may be suspected on the basis of their typical semiology. The possibility of additional PNES should also be considered if seizures fail to respond to antiepileptic drug treatment, in patients with frequent emergency admissions with seizures and in those who develop new types of seizures. The description of semiological details by patients and witnesses can suggest additional PNES. Home video recordings can support an initial diagnosis, however, especially in patients with mixed seizure disorders it is advisable to seek further diagnostic confirmation by capturing all habitual seizure types with video-EEG. The clinical features of PNES associated with epilepsy are similar to those in isolated PNES disorders and include longer duration, fluctuating course, asynchronous movements, pelvic thrusting, side-to-side head or body movement, persistently closed eyes and mouth, ictal crying, recall of ictal experiences and absence of postictal confusion. PNES can also present as syncope-like episodes with unresponsiveness and reduced muscle tone. There is no unique epileptological or brain pathology profile putting patients with epilepsy at risk of additional PNES. However, patients with epilepsy and PNES typically have lower educational achievements and higher levels of psychiatric comorbidities than patients with epilepsy alone. Psychological trauma, including sexual abuse, appears to be a less relevant aetiological factor in patients with mixed seizure disorders than those with isolated PNES, and the gender imbalance (i.e. the greater prevalence in women) is less marked in patients with PNES and additional epilepsy than those with PNES alone. PNES sometimes develop after epilepsy surgery. A diagnosis of ‘known epilepsy’ should never be accepted without (at least brief) critical review. This narrative review summarises clinical, electrophysiological and historical features that can help identify patients with epilepsy and additional PNES.

P12.01 The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide

BACKGROUND Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide. MATERIAL AND METHODS In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity. RESULTS We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI: 26–51%) versus 30% (95%CI: 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI: 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. CONCLUSION Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

Entry of antiepileptic drugs (valproate and lamotrigine) into the developing rat brain

Background: Women with epilepsy face difficult choices whether to continue antiepileptic drug treatment during pregnancy, as uncontrolled seizures carry great risk to mother and fetus but continuing treatment may have adverse effects on baby’s development. This study aimed at evaluating antiepileptic drug entry into developing brain. Methods: Anaesthetised pregnant, non-pregnant adult females, postnatal and fetal rats were injected intraperitoneally with different doses, single or in combinations, of valproate and lamotrigine, within clinical range. Injectate included 3H-labelled drug. After 30min, CSF, blood and brain samples were obtained; radioactivity measured using liquid scintillation counting. Some animals were also exposed to valproate in feed throughout pregnancy and into neonatal period. Drug levels measured by liquid chromatography coupled to mass spectrometry (LC-MS). Results given as CSF or tissue/plasma% as index of drug entry. Results: Entry of valproate into brain and CSF was higher at E19 and P4 compared to adult and was dose-dependent except at E19; placental transfer increased significantly at highest dose of 100mg/kg. Lamotrigine entry into the brain was dose dependent only at E19. Chronic valproate treatment, or combination of valproate and lamotrigine had little effect on either drug entry, except for reduced valproate brain entry in adult brain with chronic treatment. Placental transfer decreased significantly after chronic valproate treatment. LC-MS measurement of valproate in adults confirmed that rat plasma values were within the clinical range and CSF/plasma and brain/plasma ratios for LC-MS and 3H-valproate were similar. Conclusion: Results suggest that entry of valproate may be higher in developing brain, the capacity of barrier mechanism is mostly unaffected by doses within the clinical range, with or without addition of lamotrigine. Chronic valproate exposure may result in upregulation in cellular mechanisms restricting its entry into the brain. Entry of lamotrigine was little different at different ages and was not dose dependent.

The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide

Purpose Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide. Methods In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity. Results We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI 26–51%) versus 30% (95%CI 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. Conclusion Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

The Effectiveness of Antiepileptic Drug Treatment in Glioma Patients: Lamotrigine Versus Lacosamide

Purpose: Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide.Methods: In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2-4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity.Results: We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI: 26-51%) versus 30% (95%CI: 20-41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI: 0.46-1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. Conclusion: Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

Entry of antiepileptic drugs (valproate and lamotrigine) into the developing rat brain

Background: Women with epilepsy face difficult choices whether to continue antiepileptic drug treatment during pregnancy, as uncontrolled seizures carry great risk to mother and fetus but continuing treatment may have adverse effects on baby’s development. This study aimed at evaluating antiepileptic drug entry into developing brain. Methods: Anaesthetised pregnant, non-pregnant adult females, postnatal and fetal rats were injected intraperitoneally with different doses, single or in combinations, of valproate and lamotrigine, all within clinical range. Injectate included 3H-labelled drug. After 30min, CSF, blood and brain samples were obtained; radioactivity was measured using liquid scintillation counting. Some animals were also exposed to valproate in feed throughout pregnancy and into neonatal period. Drug levels were measured by liquid chromatography coupled to mass spectrometry (LC-MS). Results are given as CSF or tissue/plasma% as index of drug entry. Results: Entry of valproate into brain and CSF was higher at E19 and P4 compared to adult but was not dose-dependent; placental transfer increased significantly at highest dose of 100mg/Kg. Lamotrigine entry into the brain was dose dependent only at E19. Chronic valproate treatment, or combination of valproate and lamotrigine had little effect on either drug entry, except for reduced valproate brain entry in adult brain with chronic treatment. Placental transfer decreased significantly after chronic valproate treatment. LC-MS measurement of valproate in adults confirmed that rat plasma values were within the clinical range and CSF/plasma and brain/plasma ratios for LC-MS and 3H-valproate were similar. Conclusion: Results suggest that entry of valproate may be higher in developing brain, the capacity of barrier mechanism is mostly unaffected by doses within the clinical range, with or without addition of lamotrigine. Chronic valproate exposure may result in upregulation in cellular mechanisms restricting its entry into the brain. Entry of lamotrigine was little different at different ages and was not dose dependent.

A study of psychogenic non-epileptic seizures in an inpatient video-electroencephalography monitoring service in Tabriz, Northwest of Iran

Background: Psychogenic non-epileptic seizures (PNES) are manifested as paroxysmal alterations in motor, sensory, autonomic, and/or cognitive and behavioral signs and symptoms, without associated ictal epileptiform discharges. A misdiagnosis of PNES as epilepsy results in a prolonged and unnecessary (antiepileptic) drug treatment and social and psychological stigma of epilepsy in these patients. This study aimed to determine the epidemiology, clinical manifestations, and associated factors of PNES in hospitalized patients in the video-electroencephalography (EEG) monitoring (VEM) service of Razi Hospital, Tabriz, Iran. Methods: In this cross-sectional descriptive study, 55 patients with a final diagnosis of PNES were selected from the patients referred to the VEM unit of Razi Hospital for the evaluation of epilepsy. The study was performed from May 2017 to June 2019. Patient information included demographic data and medical history (drug history, comorbidities, trauma, and family history). The clinical manifestations (semiology and duration of attacks) and EEG findings, as recorded by VEM during hospitalization, were collected. Results: 55 patients with PNES were studied with VEM, 27 (49.1%) of which were men, and 28 (50.9%) were women. The mean and standard deviation (SD) of age of the patients was 34.16 ± 12.64 years. No significant differences were observed in the semiology of PNES between men and women. Depression was the most common psychiatric comorbidity. Conclusion: The clinical manifestations of PNES in the present study were similar to those in most previous studies from other countries. The culture and sex of the patients did not seem to be a contributing factor in PNES semiology.