Negative myoclonus causes locomotory disability in progressive myoclonus epilepsy type EPM1- Unverricht-Lundborg disease.

OBJECTIVE: Patients with Unverricht-Lundborg disease/EPM1 develop increasing locomotory disability or ataxia in the course of their disease. To test our hypothesis that negative myoclonus is the reason for this increasing ataxia, we investigated a possible correlation over time. METHODS: In 15 patients with EPM1who were confirmed to have a mutation in the CSTB gene, polygraphic video-EEG-EMG recordings were performed in freely moving or standing patients. The criterion for the duration of the negative myoclonus was the measured length of the silent periods on the EMG. RESULTS: All 15 patients had documented negative myoclonus when standing and walking. The mean duration of silent periods significantly increased from 100 (SD: 19.1) ms at time point T1 to 128 (SD: 26.6) ms at T2 in seven of eight patients, based on two recordings and a mean interval of 12.8 (SD: 4.9) years. Using a cross-sectional approach, all 15 patients were classified based on whether they were ambulatory, could walk with aid, or needed a wheelchair. Ambulatory patients had a mean duration of 97.3 (SD: 16.5) ms, patients who could walk with aid had a mean duration of 106.7 (SD: 16) ms, and patients who were wheelchair-bound had a mean duration of 138 (SD: 23.6) ms. In addition to the prolongation of the silent periods, there was an observed increase in frequency of the negative myoclonus, becoming more continuous and tremulous. SIGNIFICANCE: Using simultaneous EEG/EMG recordings in freely moving or standing patients, we have shown that the locomotor disability or ataxia is due to negative myoclonus in voluntary innervated muscles. The reason for the progression is the prolongation of the silent periods as measured by the duration of the negative myoclonus and their increase in frequency.

Minimum standards for inpatient long-term video-EEG monitoring: A clinical practice guideline of the international league against epilepsy and international federation of clinical neurophysiology.

The objective of this clinical practice guideline is to provide recommendations on the indications and minimum standards for inpatient long-term video-electroencephalographic monitoring (LTVEM). The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology develop guidelines aligned with the Epilepsy Guidelines Task Force. We reviewed published evidence using The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We found limited high-level evidence aimed at specific aspects of diagnosis for LTVEM performed to evaluate patients with seizures and nonepileptic events (see Table S1). For classification of evidence, we used the Clinical Practice Guideline Process Manual of the American Academy of Neurology. We formulated recommendations for the indications, technical requirements, and essential practice elements of LTVEM to derive minimum standards used in the evaluation of patients with suspected epilepsy using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Further research is needed to obtain evidence about long-term outcome effects of LTVEM and establish its clinical utility.

Minimum standards for inpatient long-term video-electroencephalographic monitoring: A clinical practice guideline of the International League Against Epilepsy and International Federation of Clinical Neurophysiology.

The objective of this clinical practice guideline is to provide recommendations on the indications and minimum standards for inpatient long-term video-electroencephalographic monitoring (LTVEM). The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology develop guidelines aligned with the Epilepsy Guidelines Task Force. We reviewed published evidence using the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement. We found limited high-level evidence aimed at specific aspects of diagnosis for LTVEM performed to evaluate patients with seizures and nonepileptic events. For classification of evidence, we used the Clinical Practice Guideline Process Manual of the American Academy of Neurology. We formulated recommendations for the indications, technical requirements, and essential practice elements of LTVEM to derive minimum standards used in the evaluation of patients with suspected epilepsy using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Further research is needed to obtain evidence about long-term outcome effects of LTVEM and to establish its clinical utility.

Sensitivity of long-term EEG monitoring as a second diagnostic step in the initial diagnosis of epilepsy.

In this retrospective study, we aimed to evaluate the sensitivity and negative predictive value of long-term EEG (L-EEG) in patients being assessed for epilepsy, who had already undergone non-specific standard EEG(s) (S-EEG). Secondary endpoints of this study were: (1) the correlation of non-specific changes on EEG with epileptiform patterns on L-EEG; and (2) the correlation of clinical parameters such as subjective frequency of seizures or epileptogenic lesions on cerebral imaging with epileptiform changes on L-EEG. We retrospectively analysed clinical and electrophysiological data of 75 patients, assessed for epilepsy at the University Hospital Zurich, who had undergone an L-EEG for at least 48 hours, between 2010 and 2015. All patients had already undergone S-EEG(s) before L-EEG, which showed no epileptic changes. Furthermore, the association with clinical parameters, such as frequency of presumptive seizures, abnormalities on standard-EEG, AED intake and cerebral imaging with the final diagnosis, was analysed. Out of 75 patients, 14 (19%) patients were finally diagnosed with epilepsy. In eight of these patients, L-EEGs showed typical ictal/interictal patterns, with a sensitivity of 57% and negative predictive value of 91%. Neither the subjective frequency of seizures nor potentially epileptogenic lesions on cerebral imaging were associated with a positive epilepsy diagnosis. In this preselected cohort of patients, who had already undergone a non-diagnostic S-EEG, the sensitivity of L-EEG remained considerable. Nonetheless, our study also revealed a significant false-negative rate. Based on the high negative predictive value in this study, L-EEG appears to be most useful at excluding epilepsy. Nevertheless, thorough evaluation of seizure history and clinical findings remain crucial for a reliable diagnosis.

The medial pulvinar as a subcortical relay in temporal lobe status epilepticus.

PURPOSE: Mutual cortico-thalamic interactions are assumed to be the basis for sustained ictal activity during status epilepticus. We aimed to investigate thalamic involvement during focal status epilepticus through the analysis of ictal diffusion-weighted MR-imaging. METHODS: We retrospectively analyzed a cohort of 62 patients who received an MRI scan during an episode of focal onset status epilepticus in our center between 2001 and 2018. RESULTS: Thalamic diffusion restrictions during focal status epilepticus were found in 29 of 62 cases (46.8 %). As the most frequent localization, the medial pulvinar was affected in 22 cases (75.9 %). Temporal status epilepticus was associated with thalamic DWI-findings (20/33, 60.6 %), in particular in the medial pulvinar (18/33, 54.5 %). To the contrary, the medial pulvinar was less frequently involved in parietal (3/11, 27.3 %) and only rarely in frontal status epilepticus (1/15, 6.7 %). CONCLUSION: The medial pulvinar appears to be a frequently involved subcortical relay for maintenance of ictal activity in temporal onset focal status epilepticus. Our findings provide possible novel insights regarding the interpretation of thalamic DWI restrictions in patients with unclear neurological conditions.

Ictal nausea and vomiting - Is it left or right?

PURPOSE: Ictal nausea/vomiting has been linked to the non-dominant hemisphere and has been considered a lateralizing sign. However, small case series and single cases have reported seizure localisation in the dominant hemisphere. Here we aimed to determine the seizure localisation and lateralization in cases with ictal nausea/retching/vomiting to test the hypothesis that these signs are of lateralizing value. METHODS: We searched two large tertiary epilepsy-center video-EEG databases (period: 1980-2017) for reports on ictal nausea/retching/vomiting and retrieved ictal EEG seizure location, lateralization and clinical symptoms. RESULTS: We identified 13 patients with focal epilepsy and video-EEG-documented ictal nausea (n = 2), nausea and retching (n = 3), retching followed by vomiting (n = 5) or only vomiting (n = 3). Aetiology was genetic (n = 1), structural/metabolic (n = 7) or of unclear origin (n = 5). While in 12/13 patients epileptic discharges were temporal, a single case was parietal. A left-sided seizure origin was more frequent than a right-sided origin (62 vs. 38%). Assuming a left-sided language dominance in the single left-handed patient and in those two patients with unclear handedness (based on the known distribution of hemispheric speech-dominance), the distribution of ictal nausea/retching/vomiting to the dominant vs. non-dominant hemisphere was not significantly different from a random distribution (8 vs. 5, p = 0.581). CONCLUSION: Ictal nausea/retching/vomiting are most frequently of temporal origin. In contrast to previous studies, our ictal video-EEG data suggests that these signs have no lateralizing value. Thus, video-EEG should be performed and while this clinical sign points to a temporal seizure origin, it does not determine its lateralization.

Survival in 76 cats with epilepsy of unknown cause: a retrospective study.

Survival of cats with epilepsy of unknown cause (EUC) has not been reported. Seizure semiology and its relationship to treatment outcome and survival was studied in a population of 76 cats. A questionnaire for seizure semiology was developed based on experimental data. Seizure semiology was characterised by owner interviews at least one year after discharge. Seizures were classified as (1) primary generalised and (2) focal without and (3) with secondary generalisation. Median age at seizure onset was four (range 0.3-18) years. One-third of cats with EUC presented with primary generalised seizures and 78 per cent of those with initially focal seizures progressed to secondary generalised seizures. Clinical signs of generalised seizures included sudden onset of loss of consciousness and tonic-clonic seizures, while cats with focal seizures had unilateral signs. Antiepileptic drug (AED) therapy was initiated in 62 cats. Complete remission rate was 42 per cent and the median survival time was 3.2 (range 1-11) years with or without AED, and 91 per cent were still alive at the time of interview. Neither semiology nor seizure type predicted survival, response to treatment and outcome in cats with EUC. A seizure-free status of more than 12 months was observed in 79 per cent of cats without AED.

Persistent generalized periodic discharges: A specific marker of fatal outcome in cerebral hypoxia.

OBJECTIVES: Electroencephalography (EEG) is one of the methods used in predicting the outcome after cerebral hypoxia. In this study we aim to evaluate the significance of generalized periodic discharges (GPD) as a prognostic marker. METHODS: We retrospectively analyzed the medical histories of patients, who underwent an EEG after cardiac arrest during the time period from 2005 to 2013 at the University Hospital Zurich. All EEGs were re-interpreted using the 2012 American Clinical Neurophysiology Society (ACNS) classification for intensive care unit (ICU) EEGs. RESULTS: Out of 131 patients, in which an EEG was recorded after cardiopulmonary resuscitation, 119 were included in our study. The average interval between cardiac arrest and EEG-recording was 3.8±3.0days (range: 0-14days). Persistent GPDs (i.e. GPDs more than 24h after the event) were found in thirty-two (26.9%) of the patients initial EEGs. The appearance of persistent GPDs preceded fatal outcome in 100% of all cases (vs. 69.0% in the non-GPD-group, p<0.0001). CONCLUSION: Among other encephalopathic markers in EEG persistent GPDs are a highly specific prognostic marker of fatal outcome in patients with hypoxic encephalopathy. SIGNIFICANCE: Using standardized EEG interpretation, this study identified persistent GPDs as a specific prognostic marker in post cardiac arrest syndrome.

Automated morphometric magnetic resonance imaging analysis for the detection of periventricular nodular heterotopia.

PURPOSE: To describe a novel magnetic resonance imaging (MRI) postprocessing technique for the detection of periventricular nodular heterotopia (PNH) and to evaluate its diagnostic value. The method is a further development of voxel-based morphometric analysis with focus on a region of interest around the lateral ventricles to increase the sensitivity and specificity for automated detection of abnormally located gray matter in this area. METHODS: T(1) -weighted MRI volume data sets were normalized and segmented in statistical parametric mapping (SPM 5 software), and the distribution of gray matter was compared to a normal database. As a new approach, individual masks derived from segmentation of the lateral ventricles were used to restrict the search for ectopic gray matter to the periventricular area. PNH were automatically detected by localizing the maximum deviation from the normal database in this area, provided that the z-score exceeded a certain threshold. The optimal z-score threshold for maximum sensitivity and specificity was determined by a receiver operating characteristic (ROC) curve analysis. The method was applied in 40 patients with PNH and 400 controls. KEY FINDINGS: PNH were detected in 37 of 40 patients, and false positives were found in 34 of 400 controls, amounting to 92.5% sensitivity and 91.5% specificity. In 17 of the patients in whom PNH could be identified, these lesions had been overlooked in the past, and in 8 patients even in the high-resolution MRI subsequently used for postprocessing. SIGNIFICANCE: The results suggest that automated morphometric MRI analysis with focus on ectopic gray matter in the periventricular areas facilitates the evaluation of MRI data and increases the sensitivity for the detection of PNH.

Management and long-term outcome in patients presenting with ictal asystole or bradycardia.

PURPOSE: Ictal asystole (IA) and ictal bradycardia (IB) are rare autonomic symptoms during epileptic seizures and may be potentially life-threatening. Guidelines for the care of these patients are missing. The aim of this multicenter study was to evaluate the management and long-term outcome in patients with IA and IB. PATIENTS AND METHODS: All patients with IA and IB were included from four epilepsy centers (Bielefeld, Kork, Marburg, and Zürich) from 2002 until 2009. Using a standardized assessment form, clinical data, treatment decisions, and outcomes were extracted from patient charts and simultaneous electroencephalography/electrocardiography (EEG/ECG) recordings. KEY FINDINGS: Seizures with IA or IB were identified in 16 patients. In all patients an associated temporal seizure pattern was recorded and in 15 patients, sudden falls, fainting, or trauma was previously reported or recorded during the monitoring. In three patients (18.8%) diagnosis of focal epilepsy was newly established and anticonvulsive treatment was initiated. Two patients with refractory epilepsy underwent epilepsy surgery. In seven patients (43.8%) a cardiac pacemaker was implanted. In 14 of 16 treated patients, seizure freedom (n = 5) or absence of sudden falls, fainting, or trauma (n = 9) could be achieved. Two patients denied epilepsy surgery as well as a pacemaker and continue to have frequent falls and trauma. SIGNIFICANCE: Our study demonstrates that epilepsy surgery and antiepileptic drugs may lead to sustained freedom of seizures as well as ictal syncope. In drug-resistant patients not suitable for epilepsy surgery, implantation of a cardiac pacemaker may prevent sudden falls as well as trauma. Based on our results and previously reported cases we propose a treatment algorithm.

Brain electrical responses to high- and low-ranking buildings.

Since the ancient world, architecture generally distinguishes two categories of buildings with either high- or low-ranking design. High-ranking buildings are supposed to be more prominent and, therefore, more memorable. Here, we recorded event-related potentials (ERPs) to drawings of buildings with either high- or low-ranking architectural ornaments and found that ERP responses between 300 and 600 ms after stimulus presentation recorded over both frontal lobes were significantly more positive in amplitude to high-ranking buildings. Thus, ERPs differentiated reliably between both classes of architectural stimuli although subjects were not aware of the two categories. We take our data to suggest that neurophysiological correlates of building perception reflect aspects of an architectural rule system that adjust the appropriateness of style and content ("decorum"). Since this rule system is ubiquitous in Western architecture, it may define architectural prototypes that can elicit familiarity memory processes.

Levetiracetam-induced myoclonic status epilepticus in myoclonic-astatic epilepsy: a case report.

We report on a 3-year-old boy with myoclonic-astatic epilepsy who developed myoclonic status epilepticus with continuous twitching of the face and unresponsiveness under monotherapy with levetiracetam. Recently, a nonconvulsive status epilepticus in an adult epilepsy patient has also been described. Our observation points to the possibility of a causal relationship between the induction of myoclonic status by levetiracetam in certain patients with Doose's syndrome. However, a spontaneous evolution cannot be excluded. Levetiracetam is a well-known drug for the control of myoclonic seizures. A controlled study would provide a better understanding of any possible aggravating role in certain forms of myoclonic-astatic epilepsy.