Learn how to interpret and use intracranial EEG findings.

Epilepsy surgery is the therapy of choice for many patients with drug-resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure-onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective "1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings" of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG.

Standard procedures for the diagnostic pathway of sleep-related epilepsies and comorbid sleep disorders: an EAN, ESRS and ILAE-Europe consensus review.

BACKGROUND AND PURPOSE: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2). METHODS: The project was conducted under the auspices of the European Academy of Neurology, the European Sleep Research Society and the International League Against Epilepsy Europe. The framework entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For the literature search a stepwise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library. RESULTS: Scenario 1: Despite a low quality of evidence, recommendations on anamnestic evaluation and tools for capturing the event at home or in the laboratory are provided for specific SREs. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizure control. CONCLUSIONS: Definitive procedures for evaluating patients with SRE are lacking. Advice is provided that could be of help for standardizing and improving the diagnostic approach of specific SREs. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined.

Evidence-based recommendations for examination and diagnostic strategies of polyneuropathy electrodiagnosis.

The purpose of this report is to recommend evidence-based strategies for polyneuropathy (PNP) electrodiagnosis based on a large cohort of patients examined prospectively. Nerve conduction studies (NCS) of bilateral tibial, peroneal and sural nerves, the latter with both near-nerve-technique (NNT) and surface recordings, were done in 313 patients with clinically suspected PNP. Bilateral dorsal sural and medial plantar nerves, and unilateral median and ulnar nerves were further examined in a subgroup of patients. The final clinical diagnosis retrieved from the patients medical records 1-6 years after the neurophysiological investigation served as diagnostic reference standard. The clinical follow-up diagnosis confirmed PNP in 219 patients. The tibial nerve was the most sensitive nerve (75%), with prolonged tibial F-wave as the most sensitive parameter (72%). Sural NNT recordings were more sensitive (66%) than surface recordings (49%) (p < 0.05), however, dorsal sural (68%) and medial planter (70%) nerves had similar sensitivities as NNT. There was no side difference in the incidence of abnormality for any nerve. Based on these results, we recommend a strategy starting with tibial and sural NCS on one side for electrophysiological screening for distal symmetric PNP. If one of these is abnormal, we recommend examining the other lower and upper extremity nerves, including distal sensory nerves, particularly if NNT is not applicable. While one abnormal parameter is sufficient to interpret a nerve as abnormal, we recommend at least two abnormal nerves for PNP diagnosis, preferentially one being the sural nerve. We believe that the strategies recommended in this study may improve PNP electrodiagnosis.

Ictal and interictal electric source imaging in pre-surgical evaluation: a prospective study.

BACKGROUND AND PURPOSE: Accurate localization of the epileptic focus is essential for surgical treatment of patients with drug-resistant epilepsy. Electric source imaging (ESI) is increasingly used in pre-surgical evaluation. However, most previous studies have analysed interictal (II) discharges. Prospective studies comparing the feasibility and accuracy of II and ictal (IC) ESI are lacking. METHODS: We prospectively analysed long-term video-electroencephalography recordings (LTM) of patients admitted for pre-surgical evaluation. We performed ESI of II and IC signals using two methods, i.e. equivalent current dipole (ECD) and a distributed source model (DSM). LTM recordings employed the standard 25-electrode array (including inferior temporal electrodes). An age-matched template head model was used for source analysis. Results were compared with intracranial recordings, conventional neuroimaging methods [magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT)] and outcome at 1 year after surgery. RESULTS: A total of 87 consecutive patients were analysed. ECD gave a significantly higher proportion of patients with localized focal abnormalities (94%) compared with MRI (70%), PET (66%) and SPECT (64%). Agreement between the ESI methods and intracranial recording was moderate to substantial (k = 0.56-0.79). A total of 54 patients were operated (47 patients more than 1 year ago) and 62% of them became seizure-free. The localization accuracy of II-ESI was 51% for DSM and 57% for ECD, and that for IC-ESI was 51% for DSM and 62% for ECD. The differences between the ESI methods were not significant. Differences in localization accuracy between ESI and MRI (55%), PET (33%) and SPECT (40%) were not significant. CONCLUSIONS: The II-ESI and IC-ESI of LTM data have high feasibility and their localization accuracy is similar to that of conventional neuroimaging methods.

Clinical utility of EEG in diagnosing and monitoring epilepsy in adults.

Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline. Instead, our goal is to summarize the scientific evidence for the utility of EEG when diagnosing and monitoring PWE.

The utility of motor unit number estimation methods versus quantitative motor unit potential analysis in diagnosis of ALS.

OBJECTIVE: To compare the diagnostic utility of motor unit number estimation (MUNE) methods to motor unit potential (MUP) analysis in amyotrophic lateral sclerosis (ALS). METHODS: Twenty-five patients (1 definite, 11 probable, 9 possible ALS and 4 progressive muscular atrophy) and 22 healthy controls were prospectively included. Quantitative MUP analysis and three MUNE methods; Multiple Point Stimulation MUNE (MPS), Motor Unit Number Index (MUNIX) and MScanFit MUNE (MScan) were done in abductor pollicis brevis muscle. The sensitivities were compared by McNemar chi-square test. MUNE, MUP and revised ALS Functional Rating Scale (ALSFRS-R) parameters were correlated by regression analysis. RESULTS: The sensitivities of MPS (76%) and MScan (68%) were higher than MUP duration (36%) and amplitude (40%) in detecting motor unit loss (p < 0.05). MUNE methods increased the categorical probability from possible to probable ALS in 4 patients (16%). There was only significant correlation between ALSFRS-R and MScan (r = 0.443, p = 0.027) among the electrophysiological tests. MUNE methods did not correlate to MUP parameters. CONCLUSIONS: MUNE methods are more sensitive in showing abnormality than MUP analysis. SIGNIFICANCE: MUNE methods, in particular MScan, may have the potential to be implemented in the clinical practice for diagnosis and follow-up of neuromuscular disorders particularly ALS.

Efficacy of the Danish epilepsy surgery programme.

OBJECTIVE: Despite optimal medical treatment, approximately one-third of patients with epilepsy continue to have seizures. Epilepsy surgery is widely accepted as a therapeutic option in the selected subset of patients with drug-resistant focal epilepsy. Here, we report the results of the Danish epilepsy surgery programme from 2009 to 2014. MATERIAL AND METHODS: A total of 169 consecutive patients, operated at Rigshospitalet, were included. Information was gathered from digital patient records. Before 1-year follow-up, two patients were lost to follow-up and three were referred to new surgery. RESULTS: The median years of drug resistance before operation were 11 years. At 1-year follow-up (n = 164), seizure outcomes were as follows: 65% Engel I (free from disabling seizures), 51% Engel IA (completely seizure free) and 9% Engel IV (no worthwhile improvement), and for patients operated in the medial temporal lobe (n = 114): 70% Engel I, 56% Engel IA, 5% Engel IV. The outcomes of the 53 patients needing intracranial EEG recording (ICR) were not significantly different from the patients only evaluated with surface EEG. None of the eight MRI-negative patients operated outside the medial temporal lobe after ICR were free of disabling seizures. 12% of MTLE patients developed de novo depression after epilepsy surgery despite good surgical outcome. Three patients required rehabilitation due to post-operative hemiplegia. CONCLUSION: The outcomes of the Danish epilepsy surgery programme align with international results found in recent meta-analyses. Serious complications to epilepsy surgery are seldom. In accordance with international recommendations, Danish drug-resistant patients should be referred to epilepsy surgery evaluation at an earlier stage of the disease.

Modified automatic R-peak detection algorithm for patients with epilepsy using a portable electrocardiogram recorder.

Earlier studies have shown that short term heart rate variability (HRV) analysis of ECG seems promising for detection of epileptic seizures. A precise and accurate automatic R-peak detection algorithm is a necessity in a real-time, continuous measurement of HRV, in a portable ECG device. We used the portable CE marked ePatch® heart monitor to record the ECG of 14 patients, who were enrolled in the videoEEG long term monitoring unit for clinical workup of epilepsy. Recordings of the first 7 patients were used as training set of data for the R-peak detection algorithm and the recordings of the last 7 patients (467.6 recording hours) were used to test the performance of the algorithm. We aimed to modify an existing QRS-detection algorithm to a more precise R-peak detection algorithm to avoid the possible jitter Qand S-peaks can create in the tachogram, which causes error in short-term HRVanalysis. The proposed R-peak detection algorithm showed a high sensitivity (Se = 99.979%) and positive predictive value (P+ = 99.976%), which was comparable with a previously published QRS-detection algorithm for the ePatch® ECG device, when testing the same dataset. The novel R-peak detection algorithm designed to avoid jitter has very high sensitivity and specificity and thus is a suitable tool for a robust, fast, real-time HRV-analysis in patients with epilepsy, creating the possibility for real-time seizure detection for these patients.

Neurophysiological localisation of ulnar neuropathy at the elbow: Validation of diagnostic criteria developed by a taskforce of the Danish Society of clinical neurophysiology.

OBJECTIVE: This study validates consensus criteria for localisation of ulnar neuropathy at elbow (UNE) developed by a taskforce of the Danish Society of Clinical Neurophysiology and compares them to the existing criteria from the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). The Danish criteria are based on combinations of conduction slowing in the segments of the elbow and forearm expressed in Z-scores, and difference between the segments in m/s. Examining fibres to several muscles and sensory fibres can increase the certainty of the localisation. METHODS: Diagnostic accuracy for UNE was evaluated on 181 neurophysiological studies of the ulnar nerve from 171 peer-reviewed patients from a mixed patient-group. The diagnostic reference standard was the consensus diagnosis based on all available clinical, laboratory, and electrodiagnostic information reached by a group of experienced Danish neurophysiologists. RESULTS: The Danish criteria had high specificity (98.4%) and positive predictive value (PPV) (95.2%) and fair sensitivity (76.9%). Compared to the AANEM criteria, the Danish criteria had higher specificity (p<0.001) and lower sensitivity (p=0.02). CONCLUSIONS: The Danish consensus criteria for UNE are very specific and have high PPV. SIGNIFICANCE: The Danish criteria for UNE are reliable and well suited for use in different centres as they are based on Z-scores.

Reproducibility, and sensitivity to motor unit loss in amyotrophic lateral sclerosis, of a novel MUNE method: MScanFit MUNE.

OBJECTIVE: To examine inter- and intra-rater reproducibility and sensitivity to motor unit loss of a novel motor unit number estimation (MUNE) method, MScanFit MUNE (MScan), compared to two traditional MUNE methods; Multiple point stimulation MUNE (MPS) and Motor Unit Number Index (MUNIX). METHODS: Twenty-two ALS patients and 20 sex- and age-matched healthy controls were included. MPS, MUNIX, and MScan were performed twice each by two blinded physicians. Reproducibility of MUNE values was assessed by coefficient of variation (CV) and intra class correlation coefficient (ICC). Ability to detect motor unit loss was assessed by ROC curves and area under the curve (AUC). The times taken for each of the methods were recorded. RESULTS: MScan was more reproducible than MPS and MUNIX both between and within operators. The mean CV for MScan (12.3%) was significantly lower than for MPS (24.7%) or MUNIX (21.5%). All methods had ICC>0.94. MScan and Munix were significantly quicker to perform than MPS (6.3mvs. 13.2m). MScan (AUC=0.930) and MPS (AUC=0.899) were significantly better at discriminating between patients and healthy controls than MUNIX (AUC=0.831). CONCLUSIONS: MScan was more consistent than MPS or MUNIX and better at distinguishing ALS patients from healthy subjects. SIGNIFICANCE: MScan may improve detection and assessment of motor unit loss.

Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study.

BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. METHODS: We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. RESULTS: A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. CONCLUSIONS: Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1-positive patients presented with a classical limbic encephalitis. The majority of patients recovered well.

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".

How long shall we record electroencephalography?

BACKGROUND: The duration of electroencephalography (EEG) recordings varies widely among laboratories. Although several recommendations had been published, there are no previous studies directly addressing this. AIMS OF THE STUDY: To assess the effect of the recording duration on detection of EEG abnormalities in a tertiary referral centre for epilepsy. METHODS: We have reviewed 1005 EEG recordings and determined the shortest recording duration necessary to identify interictal EEG abnormalities. RESULTS: Standard, awake recordings shorter than 20 min yielded a significantly lower incidence of abnormal findings as compared to longer recordings. Although there was an increase in the diagnostic yield from 30 to 180 min recording duration, this failed to reach the level of significance. For sleep recordings, there was no significant increase in the diagnostic yield beyond 30 min. CONCLUSIONS: Our results provide evidence for recommending at least 20 min recording duration for standard awake EEGs and 30 min for sleep EEG recordings. As data were derived from patients referred to our epilepsy centre, the results are only valid for epilepsy-related indications.

Effectiveness of the ketogenic diet in a broad range of seizure types and EEG features for severe childhood epilepsies.

BACKGROUND: Ketogenic diet (KD) is an effective treatment for pharmacoresistant epilepsy: more than half of the patients show a greater than 50% reduction in seizures. OBJECTIVE: To identify clinical or electroencephalogram (EEG) variables predicting the response to KD. METHODS: Clinical and EEG data were retrospectively analysed from 50 consecutive patients treated by KD for severe, pharmacoresistant epilepsy. Most of the patients (70%) had retarded mental and motor development. RESULTS: Three months after the start of the KD two-thirds (33) of the patients were responders (had a more than 50% reduction in seizure frequency). The presence of epileptiform EEG discharges in the temporal region correlated with an unfavourable response (P = 0.03). The presence of bilateral synchronous epileptiform discharges, and the presence of complex partial seizures approached significance but all other variables did not. CONCLUSIONS: Our results further support that KD is efficient in a wide variety of epileptic patients with a broad range of EEG features. However, patients with epileptiform discharges in the temporal region are less likely to achieve therapeutic response.

Changes in muscle fiber density following a stroke.

OBJECTIVES: Previous studies have revealed a selective functional loss of the large, high-threshold motor units in the paretic muscles after lesion of the upper motor neuron. We set out to study the degree and the time course of the reorganization of the motor units following a stroke. METHODS: Examinations were performed on 59 patients with a unilateral ischemic stroke in the territory of the middle cerebral artery, and on 42 healthy controls. The duration of hemiparesis ranged from 2 weeks to 48 months. The fiber density (FD) in the abductor digiti minimi muscle was determined by means of single-fiber electromyography on both the hemiparetic and the unaffected side in the patients, and unilaterally in the control subjects. RESULTS: The FD was increased on the hemiparetic side relative to the unaffected side and the control group. This change correlated with the severity of the clinical signs. The FD increased during the first 10 months following the stroke and subsequently remained stable. CONCLUSIONS: The process of reinnervation in the muscles takes place in the acute phase after stroke. These changes are related to the severity of the symptoms. SIGNIFICANCE: Our findings suggest that trans-synaptic degeneration of the spinal motor neurons occurs shortly after the lesion of the upper motor neurons.

Large motor units are selectively affected following a stroke.

OBJECTIVE: Previous studies have revealed a loss of functioning motor units in stroke patients. However, it remained unclear whether the motor units are affected randomly or in some specific pattern. We assessed whether there is a selective loss of the large (high recruitment threshold) or the small (low recruitment threshold) motor units following a stroke. METHODS: Forty-five stroke patients and 40 healthy controls participated in the study. Macro-EMG was recorded from the abductor digiti minimi muscle at two levels of force output (low and high). The median macro motor unit potential (macro-MUP) amplitude on the paretic side was compared with those on the unaffected side and in the controls. RESULTS: In the control group and on the unaffected side, the macro-MUPs were significantly larger at the high force output than at the low one. However, on the paretic side the macro-MUPs at the high force output had the same amplitude as those recorded at the low force output. These changes correlated with the severity of the paresis. CONCLUSIONS: Following a stroke, there is a selective functional loss of the large, high-threshold motor units. These changes are related to the severity of the symptoms. SIGNIFICANCE: Our findings furnish further insight into the pathophysiology of the motor deficit following a stroke.

Evidence-based pharmacological treatment of neuropathic pain syndromes.

Neuropathic pain, caused or initiated by a primary lesion in the peripheral or central nervous system, can result in a dramatic reduction in the patient's quality of life. The expression neuropathic pain covers a heterogeneous group of conditions, including peripheral neuropathy, complex regional pain syndrome, trigeminal neuralgia and central pain. Neuropathic pain poorly responds to conventional analgesics. However, with appropriate therapy, a significant proportion of patients experience a substantial pain reduction. We present here an evidence-based review of the options for the treatment of neuropathic pain syndromes. Consideration is given to the mechanisms of action, numbers needed to treat (NNT), the recommended doses and the most frequent side-effects of the drugs for which consistent support has been found for treatment of these pain conditions.