A European questionnaire survey on epilepsy monitoring units' current practice for postoperative psychogenic nonepileptic seizures' detection.

BACKGROUND: In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES. METHODS: We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databases to allow extraction of cases with postoperative PNES, the data that these bases could provide, and EMUs' interest to participate in a retrospective postoperative PNES project. RESULTS: Twenty EMUs completed the questionnaire sheet. The number of patients operated every year/per center is 26.7 ( ±â€¯19.1), and systematic preoperative and postoperative psychiatric evaluation is performed in 75% and 50% of the EMUs accordingly. Sexual or other abuse is systematically recorded in one-third of the centers, and the mean follow-up period after epilepsy surgery is 10.5 ±â€¯7.5 years. In suspected postoperative PNES, video-EEG is performed in 85% and psychiatric assessment in 95% of the centers. An electronic database to allow extraction of patients with PNES after epilepsy surgery is used in 75% of the EMUs, and all EMUs that sent the sheet completed expressed their interest to participate in a retrospective postoperative PNES project. CONCLUSION: Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES.

Magnetoencephalographic study of hand and foot sensorimotor organization in 325 consecutive patients evaluated for tumor or epilepsy surgery.

OBJECTIVES: The presence of intracranial lesions or epilepsy may lead to functional reorganization and hemispheric lateralization. We applied a clinical magnetoencephalography (MEG) protocol for the localization of the contralateral and ipsilateral S1 and M1 of the foot and hand in patients with non-lesional epilepsy, stroke, developmental brain injury, traumatic brain injury and brain tumors. We investigated whether differences in activation patterns could be related to underlying pathology. METHODS: Using dipole fitting, we localized the sources underlying sensory and motor evoked magnetic fields (SEFs and MEFs) of both hands and feet following unilateral stimulation of the median nerve (MN) and posterior tibial nerve (PTN) in 325 consecutive patients. The primary motor cortex was localized using beamforming following a self-paced repetitive motor task for each hand and foot. RESULTS: The success rate for motor and sensory localization for the feet was significantly lower than for the hands (motor_hand 94.6% versus motor_feet 81.8%, p < 0.001; sensory_hand 95.3% versus sensory_feet 76.0%, p < 0.001). MN and PTN stimulation activated 86.6% in the contralateral S1, with ipsilateral activation < 0.5%. Motor cortex activation localized contralaterally in 76.1% (5.2% ipsilateral, 7.6% bilateral and 11.1% failures) of all motor MEG recordings. The ipsilateral motor responses were found in 43 (14%) out of 308 patients with motor recordings (range: 8.3-50%, depending on the underlying pathology), and had a higher occurrence in the foot than in the hand (motor_foot 44.8% versus motor_hand 29.6%, p = 0.031). Ipsilateral motor responses tended to be more frequent in patients with a history of stroke, traumatic brain injury (TBI) or developmental brain lesions (p = 0.063). CONCLUSIONS: MEG localization of sensorimotor cortex activation was more successful for the hand compared to the foot. In patients with neural lesions, there were signs of brain reorganization as measured by more frequent ipsilateral motor cortical activation of the foot in addition to the traditional sensory and motor activation patterns in the contralateral hemisphere. The presence of ipsilateral neural reorganization, especially around the foot motor area, suggests that careful mapping of the hand and foot in both contralateral and ipsilateral hemispheres prior to surgery might minimize postoperative deficits.

High frequency oscillations in the intra-operative ECoG to guide epilepsy surgery ("The HFO Trial"): study protocol for a randomized controlled trial.

BACKGROUND: Intra-operative electrocorticography, based on interictal spikes and spike patterns, is performed to optimize delineation of the epileptogenic tissue during epilepsy surgery. High frequency oscillations (HFOs, 80-500 Hz) have been identified as more precise biomarkers for epileptogenic tissue. The aim of the trial is to determine prospectively if ioECoG-tailored surgery using HFOs, instead of interictal spikes, is feasible and will lead to an equal or better seizure outcome. METHODS\ DESIGN: We present a single-blinded multi-center randomized controlled trial "The HFO Trial" including patients with refractory focal epilepsy of all ages who undergo surgery with intra-operative electrocorticography. Surgery is tailored by HFOs (arm 1) or interictal spikes (arm 2) in the intra-operative electrocorticography. Primary outcome is post-operative outcome after 1 year, dichotomized in seizure freedom (Engel 1A and 1B) versus seizure recurrence (Engel 1C-4). Secondary outcome measures are the volume of resected tissue, neurologic deficits, surgical duration and complications, cognition and quality of life. The trial has a non-inferiority design to test feasibility and at least equal performance in terms of surgical outcome. We aim to include 78 patients within 3 years including 1 year follow-up. Results are expected in 2018. DISCUSSION: This trial provides a transition from observational research towards clinical interventions using HFOs. We address methodological difficulties in designing this trial. We expect that the use of HFOs as a biomarker for tailoring will increase the success rate of epilepsy surgery while reducing resection volume. This may reduce neurological deficits and yield a better quality of life. Future technical developments, such as validated automatic online HFO identification, could, together with the attained clinical knowledge, lead to a new objective tailoring approach in epilepsy surgery. TRIAL REGISTRATION: This trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02207673 (31 July 2014) and the Central Committee on Research Involving Human Subjects, The Netherlands #NL44257.041.13 (18 March 2014).

Severe Neonatal Epileptic Encephalopathy and KCNQ2 Mutation: Neuropathological Substrate?

BACKGROUND: Neonatal convulsions are clinical manifestations in a heterogeneous group of disorders with different etiology and outcome. They are attributed to several genetic causes. METHODS: We describe a patient with intractable neonatal seizures who died from respiratory compromise during a status epilepticus. RESULTS: This case report provides electroencephalogram (EEG), MRI, genetic analysis, and neuropathological data. Genetic analysis revealed a de novo heterozygous missense mutation in the KCNQ2 gene, which encodes a subunit of a voltage-gated potassium channel. KCNQ2 gene mutation is associated with intractable neonatal seizures. EEG, MRI, data as well as mutation analysis have been described in other KCNQ2 cases. Post-mortem neuropathological investigation revealed mild malformation of cortical development with increased heterotopic neurons in the deep white matter compared to an age-matched control subject. The new finding of this study is the combination of a KCNQ2 mutation and the cortical abnormalities. CONCLUSION: KCNQ2 mutations should be considered in neonates with refractory epilepsy of unknown cause. The mild cortical malformation is an important new finding, though it remains unknown whether these cortical abnormalities are due to the KCNQ2 mutation or are secondary to the refractory seizures.

[Reversible neurological deficit years after high grade glioma--the SMART syndrome]. / Reversibele neurologische uitval jaren na hooggradig glioom: het SMART-syndroom.

BACKGROUND: Survival in patients with high grade glioma has been extended in recent years as a result of more intensive therapy. As a consequence, more late term complications of treatment may be observed. CASE DESCRIPTION: A 69-year-old woman presented at the outpatient department of Neurology with headache and loss of strength in the left arm. She had been treated 7 years previously for a high grade glioma with resection and radiotherapy. One year later she had received chemotherapy for a local recurrence. Since then she was free of complaints. At investigation a left sided hemiparesis was found. As recurrence of the tumour was suspected, MR imaging of the brain was performed, which showed abnormalities suggestive for the so called 'stroke-like migraine attacks after radiotherapy' (SMART) syndrome. The further clinical course, with spontaneous recovery of strength within a few weeks and the regression of the cortical hyperintensity on MRI, confirmed the probable diagnosis. CONCLUSION: The SMART syndrome is a relatively unknown condition and should be included in the differential diagnosis in patients who present with new complaints long after cerebral radiotherapy.

'Functional connectivity' is a sensitive predictor of epilepsy diagnosis after the first seizure.

BACKGROUND: Although epilepsy affects almost 1% of the world population, diagnosis of this debilitating disease is still difficult. The EEG is an important tool for epilepsy diagnosis and classification, but the sensitivity of interictal epileptiform discharges (IEDs) on the first EEG is only 30-50%. Here we investigate whether using 'functional connectivity' can improve the diagnostic sensitivity of the first interictal EEG in the diagnosis of epilepsy. METHODOLOGY/PRINCIPAL FINDINGS: Patients were selected from a database with 390 standard EEGs of patients after a first suspected seizure. Patients who were later diagnosed with epilepsy (i.e. > or = two seizures) were compared to matched non-epilepsy patients (with a minimum follow-up of one year). The synchronization likelihood (SL) was used as an index of functional connectivity of the EEG, and average SL per patient was calculated in seven frequency bands. In total, 114 patients were selected. Fifty-seven patients were diagnosed with epilepsy (20 had IEDs on their EEG) and 57 matched patients had other diagnoses. Epilepsy patients had significantly higher SL in the theta band than non-epilepsy patients. Furthermore, theta band SL proved to be a significant predictor of a diagnosis of epilepsy. When only those epilepsy patients without IEDs were considered (n = 74), theta band SL could predict diagnosis with specificity of 76% and sensitivity of 62%. CONCLUSION/SIGNIFICANCE: Theta band functional connectivity may be a useful diagnostic tool in diagnosing epilepsy, especially in those patients who do not show IEDs on their first EEG. Our results indicate that epilepsy diagnosis could be improved by using functional connectivity.

An electro-encephalogram beta gap after induction with diazepam: a localization method in epileptogenic lesions.

OBJECTIVE: We clinically tested a quantitative EEG method to localize abnormal variations in benzodiazepine-induced fast rhythms to localize focal epileptogenic lesions, assuming altered quality/quantity of GABA receptors in the lesions. METHODS: During a 64-channel-EEG (sampled at 1 kHz) recording benzodiazepines were administered to five patients with localization related epilepsy associated with an MRI visible focal lesion. We determined the post-injection dominant spectral modulation using Gabor wavelets and analysed the symmetry of spatial distribution. This was compared to the localization of the lesion on the MRI scan. RESULTS: The principal component was found in the beta/gamma band. In all patients one region of decreased change was associated with the lesional hemisphere, and overlapped with the site of the lesion in four. Three patients underwent surgery: interictal corticographic findings concurred with the area of decreased benzodiazepine response. CONCLUSIONS: This simple method localized abnormal function associated with epileptogenic lesions. Further methodological validation is now justified. Final clinical validation must be done in MRI-negative cases as well. SIGNIFICANCE: This research may lead to techniques for non-invasive easy localization of epileptogenic tissue that is not visible on a structural MRI scan.