Salzburg Consensus Criteria for Non-Convulsive Status Epilepticus--approach to clinical application.

BACKGROUND: Salzburg Consensus Criteria for diagnosis of Non-Convulsive Status Epilepticus (SCNC) were proposed at the 4th London-Innsbruck Colloquium on status epilepticus in Salzburg (2013). METHODS: We retrospectively analyzed the EEGs of 50 consecutive nonhypoxic patients with diagnoses of nonconvulsive status epilepticus (NCSE) at discharge and 50 consecutive controls with abnormal EEGs in a large university hospital in Austria. We implemented the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology, 2012 version (ACNS criteria) to increase the test performance of SCNC. In patients without preexisting epileptic encephalopathy, the following criteria were applied: (1) more than 25 epileptiform discharges (ED) per 10-second epoch, i.e., >2.5/s and (2) patients with EDs ≤ 2.5/s or rhythmic delta/theta activity (RDT) exceeding 0.5/s AND at least one of the additional criteria: (2a) clinical and EEG improvements from antiepileptic drugs (AEDs), (2b) subtle clinical phenomena, or (2c) typical spatiotemporal evolution. In case of fluctuation without evolution or EEG improvement without clinical improvement, "possible NCSE" was diagnosed. For identification of RDT, the following criteria were compared: (test condition A) continuous delta-theta activity without further rules, (B) ACNS criterion for rhythmic delta activity (RDA), and (C) ACNS criteria for RDA and fluctuation. RESULTS: False positive rate in controls dropped from 28% (condition A) to 2% (B) (p = 0.00039) and finally to 0% (C) (p = 0.000042). Application of test condition C in the group with NCSE gives one false negative (2%). Various EEG patterns were found in patients with NCSE: (1) 8.2%, (2a) 2%, (2b) 12.2%, and (2c) 32.7%. Possible NCSE was diagnosed based on fluctuations in 57.1% and EEG improvement without clinical improvement in 14.2%. CONCLUSION: The modified SCNC with refined definitions including the ACNS terminology leads to clinically relevant and statistically significant reduction of false positive diagnoses of NCSE and to minimal loss in sensitivity. This article is part of a Special Issue entitled "Status Epilepticus".

Predicting outcome of status epilepticus.

BACKGROUND: Status epilepticus (SE) is a frequent neurological emergency complicated by high mortality and often poor functional outcome in survivors. The aim of this study was to review available clinical scores to predict outcome. METHODS: Literature review. PubMed Search terms were "score", "outcome", and "status epilepticus" (April 9th 2015). Publications with abstracts available in English, no other language restrictions, or any restrictions concerning investigated patients were included. RESULTS: Two scores were identified: "Status Epilepticus Severity Score--STESS" and "Epidemiology based Mortality score in SE--EMSE". A comprehensive comparison of test parameters concerning performance, options, and limitations was performed. Epidemiology based Mortality score in SE allows detailed individualization of risk factors and is significantly superior to STESS in a retrospective explorative study. In particular, EMSE is very good at detection of good and bad outcome, whereas STESS detecting bad outcome is limited by a ceiling effect and uncertainty of correct cutoff value. Epidemiology based Mortality score in SE can be adapted to different regions in the world and to advances in medicine, as new data emerge. In addition, we designed a reporting standard for status epilepticus to enhance acquisition and communication of outcome relevant data. A data acquisition sheet used from patient admission in emergency room, from the EEG lab to intensive care unit, is provided for optimized data collection. CONCLUSION: Status Epilepticus Severity Score is easy to perform and predicts bad outcome, but has a low predictive value for good outcomes. Epidemiology based Mortality score in SE is superior to STESS in predicting good or bad outcome but needs marginally more time to perform. Epidemiology based Mortality score in SE may prove very useful for risk stratification in interventional studies and is recommended for individual outcome prediction. Prospective validation in different cohorts is needed for EMSE, whereas STESS needs further validation in cohorts with a wider range of etiologies. This article is part of a Special Issue entitled "Status Epilepticus".

Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit.

INTRODUCTION: In refractory status epilepticus (SE), because of subcellular maladaptive changes, GABAergic drugs are no longer effective, and the excitatory neurotransmitter glutamate (Glu) plays a major role in seizure perpetuation. Perampanel (PER, licensed since 09/2012) is the first orally active noncompetitive AMPA receptor antagonist for adjunctive treatment of refractory focal epilepsy. METHODS: We analyzed treatment response, seizure outcome, and adverse effects of add-on treatment with perampanel in patients with refractory status epilepticus in the Neurological Intensive Care Unit (NICU), Salzburg, Austria between 09/2012 and 11/2014 by retrospective chart review. RESULTS: Twelve patients (75% women) with refractory status epilepticus were treated with PER administered per nasogastric tube between 09/2012 and 11/2014. Median age was 75 years [range: 60-91]. The most frequent SE type was nonconvulsive SE (NCSE) with (5/12, 42%) and without coma (6/12, 50%). In seven patients (58%), SE arose de novo, with an acute symptomatic cause in five patients (42%). Cerebrovascular diseases (4/12, 33%) and cerebral tumors (4/12, 33%) were the most common etiologies. Perampanel was given after a median number of four antiepileptic drugs [range: 2-7] and a median time of 1.5 days [range: 0.8-18.3]. In one patient (8%), clinical improvement was observed within 24h and EEG improvement within 60 h after administration of PER, while in another patient (8%), clinical and EEG improvement was observed more than 48 h after administration. Median initial dose was 4 mg [range: 2-12; SD: 4.11], titrated up to a median of 12 mg [range: 4-12] in steps of 2 to 4 mg per day. No adverse effects were reported regarding cardiorespiratory changes or laboratory parameters. Outcomes after SE were moderate disability in five patients (42%), death in three patients (25%), and persistent vegetative state in two patients (17%). CONCLUSION: Though glutamate plays a major role in seizure perpetuation, the noncompetitive AMPA receptor antagonist PER could only ameliorate seizure activity in a few patients with refractory SE. The long duration of SE before the administration of PER via nasogastric tube, as well as relatively low doses of PER, might be responsible for the modest result. Perampanel was well tolerated, and no adverse events were reported. This article is part of a Special Issue entitled Status Epilepticus.

Epidemiology-based mortality score in status epilepticus (EMSE).

BACKGROUND: Status epilepticus (SE) is a neurological emergency with high mortality and often a poor functional outcome amongst survivors. So far, only status epilepticus severity score (STESS) is available to predict individual outcomes. STESS is based on weighted sum scores of age, type of seizure, level of consciousness and history of previous seizures. Weighting factors were based on a priori assumptions. METHODS: We tested in an explorative, hypothesis generating approach, whether epidemiological data (i.e. mortality rates) can be combined to form a score (Epidemiology-based Mortality score in SE-EMSE), and further, which combination of aetiology, age, comorbidity, EEG, duration and level of consciousness yields highest test performance. Positive and negative predictive value, and correctly classified were compared to STESS (with different cut-off levels: STESS-3, STESS-4). Score points for each parameter, e.g. age, were derived from previously published specific mortality rates. For each combination of parameters, the lowest sum-score of deceased individuals was taken as cut-off. Ninety-two consecutive non-hypoxic patients (age range 20-90 years), with various forms of SE admitted to a tertiary care neurological intensive care unit were investigated retrospectively. RESULTS: EMSE using a combination of aetiology, age, comorbidity and EEG (NPV = 100 %, PPV = 68.8 %, correctly classified 89.1 %) was superior to STESS-3 and STESS-4 (p = 0.0022 or lower). CONCLUSION: EMSE explained individual mortality in almost 90 % of cases, and performed significantly better than previous scores. This explorative study needs external prospective corroboration. EMSE may be a valuable tool for risk stratification in interventional studies in the future.

Cerebral vasospasm following temporal lobe epilepsy surgery.

OBJECTIVE: Selective amygdalohippocampectomy (AHE) has been associated with postoperative cerebral vasospasm (CVS) in patients with medically intractable temporal lobe epilepsy. The incidence in temporal lobe resection (TLR) is unknown. This retrospective cohort study evaluates the incidence of and risk factors for the development of CVS in patients with TLR and AHE. METHODS: A total of 119 patients were included between 1998 and 2009. All patients were evaluated by standardized preoperative and postoperative transcranial Doppler sonography (TCD) evaluations and neurologic examinations. Postoperative CT scans were evaluated by an independent radiologist and the volume of bleeding within the resection cavity was quantified. RESULTS: Of 107 patients with longitudinal TCD data, 35 (32.7%) developed postoperative CVS. The incidence of CVS did not differ between patients with TLR and AHE. CVS was associated with female gender and a higher bleeding volume in the postoperative CT scan (p = 0.035 and 0.046). Patients with CVS showed a significantly higher incidence of postoperative neurologic signs and symptoms (48.6%) compared to patients without CVS (25%, p = 0.015). The mean length of stay was significantly prolonged in patients with diffuse CVS compared to patients with localized CVS or no CVS (28.8 ± 10.9, 24.2 ± 6.6, and 18.2 ± 6.1 days, p < 0.001). CONCLUSION: CVS is a frequent complication of surgery for temporal lobe epilepsy irrespective of the resection method. Important risk factors for the development of postoperative CVS are female gender and a higher amount of bleeding in the postoperative CT. Patients with CVS more frequently have neurologic signs and symptoms resulting in prolonged hospital stay.

Idiopathic generalised epilepsy of late onset: a separate nosological entity?

AIM: Seizure onset in idiopathic generalised epilepsies (IGE) is considered to be rare after the second decade of life. The authors aimed to explore age of seizure onset in patients with IGE and compare 'classical' onset to late onset cases. METHODS: Patients with IGE, treated at the outpatient epilepsy clinic (Medical University of Innsbruck, Austria, 1985-2006, n=798) were retrospectively screened. The inclusion criteria were: diagnosis of IGE, more than two follow-up (FU) visits, duration of FU more than 1 year and normal brain imaging. The authors analysed demographic data, age of seizure onset, seizure types, syndromes, neuroimaging and EEG findings, seizure triggers and seizure freedom for 1 and 5 years at last FU. RESULTS: A total of 492 patients (mean age at seizure onset 14.6 years, range 0.1-55, SD 7.9) with IGE were identified: childhood absence epilepsy (n=113, range 1-55, SD 6.5), juvenile absence epilepsy (n=75, range 4-39, SD 5.1), juvenile myoclonic epilepsy (n=112, range 2-39, SD 5.7), and epilepsy with grand mal seizures on awakening (n=192 range 1-52, SD 17.3). Population was stratified into three groups: 28 patients with seizure onset at >30 years, 180 patients between 15 and 30 years and 284 patients <15 years. The distribution of seizure types and epilepsy syndromes differed significantly in a group comparison (p<0.001); seizure outcome and other clinical variables did not differ throughout the groups. CONCLUSION: Apart from age-related onset of seizure types and syndromes with a loose upper limit of onset age, patients with a late onset did not differ from their younger counterparts. These data do not support the view of IGE of late onset as a separate syndrome.

Hippocampal abnormalities in malformations of cortical development: MRI study.

OBJECTIVES: Hippocampal abnormalities may coexist with malformations of cortical development (MCD). This cross-sectional MRI study aimed at categorizing hippocampal abnormalities in a large group of MCD and comparing MCD patients with (group W) and without (group W/O) hippocampal abnormalities. METHODS: Hippocampal anatomy, rotation, size, internal structure, and MRI signal alterations were assessed visually by 3 independent raters in patients with MCD and epilepsy. Four types of hippocampal abnormalities were examined in 220 patients (116 women, mean age 31 +/- 16.6, range 2-76 years): partially infolded/hypoplastic hippocampus (HH), hippocampal sclerosis (HS), malrotated hippocampus (MH), and enlarged hippocampus (EH). The commonest MCD in the cohort were focal cortical dysplasia (27%), polymicrogyria (PMG) (21%), developmental tumors (15%), and periventricular nodular heterotopia (PNH) (14%). RESULTS: Hippocampal abnormalities were seen in 69/220 (31%) patients: HH in 34/69 (49%); HS in 18/69 (26%); MH in 15/69 (22%); and EH in 2/69 (3%). PNH (21/30 [70%]) and PMG (22/47 [47%]) were most commonly associated with hippocampal abnormalities. Compared to the W/O group, patients in the W group had a higher rate of learning disability (W 41/69 [59%] vs W/O 56/151 [37%]; p = 0.003) and delayed developmental milestones (W 36/69 [52%] vs W/O 53/151 [35%]; p = 0.025); groups did not differ otherwise with regard to clinical presentation. HH was associated with symptomatic generalized epilepsies (11/34 [32%]) and high rate of learning disability (27/34 [79%]), neurologic deficits (25/34 [73%]), and delayed developmental milestones (23/34 [68%]). CONCLUSIONS: About a third of patients with malformations of cortical development had hippocampal abnormalities. Patients with hypoplastic hippocampus had the most severe clinical phenotype.

Integration of multimodality imaging and surgical navigation in the management of patients with refractory epilepsy. A pilot study using a new minimally invasive reference and head-fixation system.

OBJECTIVE: To review the experience with a new system (VBH system) for minimally invasive frameless stereotactic guidance, acting as a common platform to provide multimodal image integration and surgical navigation in a consecutive series of 25 patients who underwent surgery for drug-resistant seizures. METHODS: The usefulness of the VBH system for integrating all images to produce one dataset and for intraoperative instrument guidance and navigation was judged semiquantitatively in a three-tiered scale (+, ++, +++). Seizure outcome was classified according to Engel. RESULTS: The presurgical evaluation extended over 21.2 months (mean). A total of 141 registrations of images were performed (mean 5.6 per patient, range: 2 to 16). In 19 (76%) of 25 patients structural data fused with functional data were used for the presurgical workup. Six patients proceeded directly to navigated resection. Nineteen patients (76%) underwent invasive recording, of whom 13 underwent resective surgery. In seven patients (28%) the combination of multimodal image fusion and intra-operative stereotactic guidance was judged "essential" (+++) to remove the epileptogenic zone. Integration of all images to form one dataset was "essential" (+++) for decision making in 15 and "helpful" (++) in 4 patients (overall 76% of patients). Intraoperative use of frameless neuronavigation was "essential" (+++) in ten and "helpful" (++) in all remaining patients. Eighty percent of the patients achieved satisfactory seizure outcome after 1 year. CONCLUSION: The VBH system is a safe and effective non-invasive tool for repetitive imaging, multimodal image fusion and frameless stereotactic surgical navigation in candidates for epilepsy surgery.

Flexibility of head positioning and head fixation provided by a novel system for non-invasive maxillary fixation and frameless stereotaxy: technical note.

OBJECTIVE: The aim of this study was to demonstrate the flexibility in patient positioning and head fixation provided by a newly developed, minimally invasive upper jaw fixation device in combination with standard navigation software. TECHNIQUE: The Vogele-Bale-Hohner (VBH) headholder and the Stereotactic Intervention and Planning Laboratory (SIP-Lab) Innsbruck reference frame, were applied in epilepsy surgery requiring stereotactic guidance. The system can be adapted to various positioning and instrument guidance requirements. Instrument holders can be fixed either to a base plate or directly to the mouthpiece. When used together with a head clamp and a stabilizing arm, there are no restrictions on patient positioning. When used with the non-invasive headholder, only the supine position is well-suited for use with the described guidance instrumentation. The system can also be used with the head placed on the horseshoe headholder without altering navigation support. CONCLUSION: The VBH mouthpiece combined with an external registration frame is a flexible tool that permits patient positioning and neuronavigation with the head either fixed with a head clamp, or restrained non-invasively with a headholder, or not fixed at all. This might be advantageous within the context of epilepsy surgery.

Tuberous sclerosis complex with unilateral perisylvian polymicrogyria and contralateral hippocampal sclerosis - a case report.

Malformations of cortical development (MCD) encompass a wide spectrum of brain disorders. Although rare, the combination of certain MCD may occur. We report a rare case of combination of three distinct cerebral pathologies: tuberous sclerosis, polymicrogyria and hippocampal sclerosis in a patient with intractable epilepsy. Ictal EEG and ictal SPECT suggested right perisylvian area as a seizure onset zone. However, on MRI multiple potentially epileptogenic lesions were identified. The neurobiological background of the coexistence of different types of malformations of cortical development remains enigmatic.

Electroclinical and imaging findings in ulegyria and epilepsy: a study on 25 patients.

PURPOSE: Ulegyria refers to cerebral cortex scarring, which results from a perinatal ischaemic brain injury. It presents with a characteristic gyral pattern: small circumvolutions with atrophy at sulci bottom and spared apex. Ulegyria is frequently associated with epilepsy, cerebral palsy and mental disability. We analysed electroclinical and MRI features in patients with ulegyria and epilepsy. PATIENTS AND METHODS: We reviewed 25 patients (14 males/11 females) with ulegyria and epilepsy from the database (about 5000 patients with epilepsy) of our unit. Patients were examined clinically, underwent high resolution MRI, EEG recordings, positron emission tomography, single photon emission computed tomography and neuropsychological testing. Two patients with refractory seizures underwent epilepsy surgery. RESULTS: Mean age of patients was 34 years (5-66) at the reassessment time. The majority (16/25, 64%) had a history of perinatal asphyxia. 15 patients had delayed developmental milestones; 20 had learning disabilities and five patients were severely disabled. Mean age at seizure onset was 4.2 years (1-18). 17 patients (68%) had medically intractable epilepsy. 11 patients (44%) had occipital lobe seizures. The majority (n = 24, 96%) had parieto-occipital lesions on MRI. In 13 patients (52%), ulegyria was bilateral. 12 patients (48%) had hippocampal sclerosis. Two patients underwent epilepsy surgery with an excellent postoperative outcome (Engel class IA and IC). CONCLUSION: Patients with ulegyria often have a history of perinatal asphyxia and present with pharmacoresistant seizures. Their presurgical assessment is complicated because of frequent dual pathology (hippocampal sclerosis) and bilateral lesions.

Outcome of adult patients with temporal lobe tumours and medically refractory focal epilepsy.

BACKGROUND: Tumours are a well-recognized cause of medically intractable epilepsies. Tumours represent the primary pathology in 10%-30% of patients undergoing surgical treatment for chronic epilepsy. This study examines the surgical and epileptological outcome of adults with temporal lobe tumoural epilepsy treated within a comprehensive epilepsy surgery programme. METHODS: Between 1999 and 2004, 99 consecutive patients have been operated for intractable temporal lobe epilepsy (TLE). Among these, 14 adult patients exhibited temporal lobe neoplasms associated with TLE. Every patient underwent a comprehensive presurgical evaluation including video-EEG monitoring, MRI, interictal PET scan, ictal SPECT and neuropsychological testing. Surgical strategies were determined in an interdisciplinary seizure conference and tailored to the findings of the presurgical evaluation. All patients were available for follow up at regular intervals after 3, 6, 12 months and yearly thereafter. Epileptological outcome was classified according to Engel [10] and the ILAE (International League Against Epilepsy)/systems [33]. FINDINGS: The surgical procedures performed were temporal lobe resection in 3 patients, extended lesionectomy in 4 and extended lesionectomy with resection of the temporomesial structures in 7. One patient with an astrocytoma grade III underwent a second and third operation for recurrent disease. Histological results: Astrocytoma 5 patients, ganglioglioma/gangliocytoma 5, oligodendroglioma 2, ependymoma 1 and dysembryoplastic neuroepithelial tumour (DNET) 1. Postoperative follow-up was performed after 12-74 months (mean 31). The outcome according to the Engel classification indicated class IA in 9 patients, class IC in 3, and 1 each in classes IIIA and IVA. Epileptological outcome according to the ILAE classification indicated class 1 (12 patients) and class 4 (2 patients). Surgical mortality was zero and mild permanent neurological deficits due to surgery were seen in 2 patients. Postoperatively 3 patients showed a homonymous quadrantanopia. CONCLUSIONS: Patients with drug resistant epilepsy and temporal lobe tumours should undergo evaluation in dedicated epilepsy surgery programmes.

Unilateral polymicrogyria with ipsilateral cerebral hemiatrophy: a distinct syndrome?

INTRODUCTION: There are sporadic reports of unilateral polymicrogyria with ipsilateral hemiatrophic cerebri associated with epilepsy, focal neurological deficit and mental retardation. The mechanisms which cause this condition are not well understood. The aim of our study was to delineate further, clinical and neuroimaging features of this malformation of cortical development and to explore its possible etiological background. PATIENTS AND METHODS: Four patients (two males and two females), aged from 23 to 31 years (mean age range 27.5 years) were evaluated. Subjects underwent clinical, electrophysiological, neuropsychological and high resolution magnetic resonance imaging assessment. RESULTS: No significant perinatal event or exposure to intrauterine infection was noted. None suffered from birth asphyxia or ischemic injury. The parents of two patients were first cousins. Every subject had delayed developmental milestones, mental disability and congenital, non-progressive, spastic hemiparesis. They had epilepsy with seizure-onset ranging from three months to 17 years (mean 6.8 years); two had intractable seizures. In all patients, unilateral, right-sided polymicrogyria was associated with ipsilateral cerebral hemiatrophy. Polymicrogyria involved mainly anterior perisylvian areas; occipital regions were relatively spared. CONCLUSION: The evaluated patients showed homogenous clinical and neuroimaging characteristics. We support the idea that the disorder could constitute a clinical entity with an underlying genetic cause.

Transient and permanent magnetic resonance imaging abnormalities after complex partial status epilepticus.

Epileptic seizures, especially status epilepticus can produce MRI changes. In contrast to convulsive status epilepticus (CSE), permanent parenchymal loss is not well documented with nonconvulsive status epilepticus (NCSE) and the observed MRI changes are transient. We describe a patient with non-lesional right-sided temporal lobe epilepsy with complex partial seizures and repeated episodes of untreated complex partial status epilepticus (CPSE). Diffusion-weighted MRI exhibited marked and extended signal changes within the right temporal, frontal, insular and cingulate regions. The affected areas are considered propagation pathways of temporal lobe epilepsies. After admission, the patient was treated with i.v. antiepileptic drugs. Behavioral, EEG and MRI signal changes resolved. An atrophy of the right temporal lobe not seen in the pre-status MRI examinations was observed 6 weeks after the resolution of MRI hyperintensities. Prior episodes of CPSE had been correctly treated and remained without permanent brain damage. This case report is in favour of immediate and aggressive treatment of partial NCSE in order to avoid irreversible parenchymal loss.

Gyratory seizures revisited: a video-EEG study.

PURPOSE: Gyratory seizures (GSs) have been rarely described in generalized as well as in focal epilepsies. They were defined as a rotation around the body axis during a seizure for at least 180 degrees. The mechanisms of generation are unknown and have been discussed controversially. The aim of this investigation was to further delineate seizure semiology and assess a possible lateralizing and localizing value of GSs. METHODS: The authors screened 277 consecutive patients with intractable epilepsies referred to a University Hospital for presurgical evaluation between 1998 and 2004 for GSs: 169 had temporal lobe epilepsy (TLE), 47 frontal lobe epilepsy (FLE), 38 generalized epilepsies (GE), and 23 had extratemporal or multifocal epilepsy. RESULTS: Twelve patients showed gyratory movements in 17 seizures. Eight had FLE and four TLE (p < 0.001). In 58% (7/12), the gyratory movement was initiated by a forced versive movement of the head followed by a rotation toward the contralateral side of seizure onset. In 42% (5/12), the gyratory movement was not preceded by a forced head version. In these seizures, the direction of the rotation was toward the side of seizure onset. CONCLUSIONS: The direction of rotation lateralizes seizure onset zone in focal epilepsy depending on the seizure evolution: 1) gyratory seizures (GSs) starting with a forced version of the head ensuing into a body rotation lateralize seizure onset zone contralateral to the direction of rotation. 2) In GSs without a preceding gyratory forced head version, the direction of rotation is toward the side of seizure onset. GSs occur more frequently in frontal lobe epilepsy than temporal lobe epilepsy, while none of our patients with GSs had generalized epilepsies.