Clinical course and variability of non-Rasmussen, nonstroke motor and sensory epilepsia partialis continua: a European survey and analysis of 65 cases.

PURPOSE: To gain new insights into the clinical presentation, causes, treatment and prognosis of epilepsia partialis continua (EPC), and to develop hypotheses to be tested in a prospective investigation. METHODS: In this retrospective multicenter study, all cases were included that fulfilled these criteria: constantly repeated fragments of epileptic seizures, with preserved consciousness, lasting ≥ 1 h and representing locally restricted motor or sensory epileptic activity. Single episodes were included when they lasted for a minimum of 1 day. EPC with Rasmussen syndrome and acute stroke were excluded. KEY FINDINGS: Three time courses with two subtypes each were distinguished, that is, EPC as a solitary event (de novo or in preexistent epilepsy); chronic repetitive nonprogressive EPC (with frequent or rare episodes); and chronic persistent nonprogressive EPC (primarily or evolving out of an episodic course). These were unrelated to etiologies (morphologic lesions 34%, inflammatory 29%, systemic disorders 9%, idiopathic 5%, unknown 23%). Precipitation and inhibition of seizures is a frequent feature of EPC. Levetiracetam and topiramate have improved the possibilities for pharmacotherapy. Topiramate seems to be particularly effective with dysontogenetic etiologies. SIGNIFICANCE: The existence of several clearly distinct courses of nonprogressive EPC is a new finding. These distinctions will be further investigated in a prospective study with precise protocols for electroencephalography (EEG), imaging, and other studies. This should better establish the relation of motor and somatosensory EPC; further clarify the relations, pathogenesis, and significance of the different types and their etiologies; and possibly identify more semiologic variants. It should also provide more precise knowledge about therapy and modification of ictogenesis by external stimuli.

Nonconvulsive Status Epilepticus: Validating the Salzburg Criteria Against an Expert EEG Examiner.

PURPOSE: Rapid and correct diagnosis of nonconvulsive status epilepticus (NCSE) is crucial for optimal treatment. However, electroencephalographic diagnosis can be challenging. Salzburg Consensus Criteria (SCC) have been proposed to facilitate correct diagnosis, but their validity needs to be further established. METHODS: We retrospectively reanalyzed the first EEG in adult patients (n = 284) referred under the suspicion of NCSE at our institution in 2014. Nonconvulsive status epilepticus or possible NCSE was diagnosed according to the SCC by an examiner specifically trained in SCC and was compared with the original diagnosis made by an expert EEG examiner, which in this context served as the reference standard, to assess the validity of the criteria. Furthermore, the clinical outcome for patients not diagnosed using SCC (false-negatives) was examined. RESULTS: Nonconvulsive status epilepticus or possible NCSE was diagnosed in 40 patients by the inexperienced reader using the SCC, blinded to other clinical data, and in 47 patients by the experienced reader, not blinded to the clinical data, who did not use SCC. There were eight false-negatives, one false-positive, 39 true-positives, and 236 true-negatives. Concordance between SCC and the reference standard was high (k = 0.88 [95% confidence interval, 0.80 to 0.96]). Four of the eight false-negatives suffered from anoxic encephalopathy. The remainder had a history of epilepsy and returned to preictal functional state. CONCLUSIONS: The SCC for NCSE implemented by an inexperienced EEG reader, blinded to all other data, yielded results highly concordant with the evaluation of EEG by an experienced reader. False-negative diagnoses were associated with postictal states or anoxic encephalopathy.

The diagnostic value of continuous EEG for the detection of non-convulsive status epilepticus in neurosurgical patients - A prospective cohort study.

OBJECTIVE: To prospectively compare the diagnostic yields of standard EEG and continuous EEG (cEEG) monitoring for the diagnosis of non-convulsive status epilepticus (NCSE) in neurosurgical patients in the intensive care unit. METHODS: We included 50 consecutive patients with clinical suspicion of NCSE due to unexplained coma or subtle clinical phenomena such as discrete myoclonus. The initial 30-minute EEG recording and the following cEEG were analyzed separately for seizure activity. Data were collected on neurosurgical diagnosis, previous diagnosis of epilepsy, current medication, level of consciousness, and outcome at discharge from the neurosurgical department. RESULTS: Recurrent electrographic seizure activity was detected in five patients. This was within the first 30 mins for three patients and on the following cEEG for two patients. Antiepileptic treatment had been initiated in three of these patients. Most of the 50 patients had severe newly acquired neurological disability at discharge. CONCLUSIONS: The prospective finding of a 10% seizure incidence was lower than reports from retrospective studies. SIGNIFICANCE: Use of cEEG led to detection of seizure activity in 2 of 50 patients (4%) and was thus a low-yield method in neurosurgical patients with suspicion of NCSE. Specific markers for patient selection for cEEG are needed.

Angiotensin-converting enzyme activity and cognitive impairment during hypoglycaemia in healthy humans.

INTRODUCTION: In type 1 diabetes increased risk of severe hypoglycaemia is associated with high angiotensin-converting enzyme (ACE) activity. We tested in healthy humans the hypothesis that this association is explained by the reduced ability of subjects with high ACE activity to maintain normal cognitive function during hypoglycaemia. METHODS: Sixteen healthy volunteers selected by either particularly high or low serum ACE activity were subjected to hypoglycaemia (plasma glucose 2.7 mmol/L). Cognitive function was assessed by choice reaction tests. RESULTS: Despite a similar hypoglycaemic stimulus in the two groups, only the group with high ACE activity showed significant deterioration in cognitive performance during hypoglycaemia. In the high ACE group mean reaction time (MRT) in the most complex choice reaction task was prolonged and error rate (ER) was increased in contrast to the low ACE group. The total hypoglycaemic symptom response was greater in the high ACE group than in the low ACE group (p=0.031). There were no differences in responses of counterregulatory hormones or in concentrations of substrates between the groups. CONCLUSION: Healthy humans with high ACE activity are more susceptible to cognitive dysfunction and report higher symptom scores during mild hypoglycaemia than subjects with low ACE activity.

A quantitative EEG and MRI analysis of intermittent temporal slowing in the elderly.

OBJECTIVE: Whereas the correlation between diffuse slowing of EEG activity and neurodegenerative diseases such as Alzheimer's disease is well established, intermittent slowing over the temporal regions, which is a frequent finding in the elderly, does not have a specific clinical correlate. In this study, we compared quantitative EEG parameters between patients with temporal slowing with no signs of neurological disease and controls to evaluate cortical function in the temporal lobes and other cerebral regions. We also compared the width of the temporal lobes on magnetic resonance imaging (MRI). METHODS: Mean dominant frequency and relative power in delta, theta, alpha, and beta frequency bands were examined in 20 patients older than 60 years with intermittent temporal slowing and 20 age-matched controls without significant lesions on MRI or medical conditions known to affect the EEG. Furthermore, the correlation between the frequency of temporal slowing and the mean dominant frequency and the width of the medial temporal lobes on MRI were examined. RESULTS: Mean dominant frequency and the relative power in the beta frequency band was lower in patients with temporal slowing than in controls in all of the cortical regions examined. No significant correlation was found between the frequency of slowing and the mean dominant frequency. There was no significant difference in the width of the medial temporal lobes. CONCLUSIONS: Intermittent temporal slowing was correlated with diffusely reduced mean dominant frequency and a shift in relative power to lower frequency bands. SIGNIFICANCE: The results suggest that subclinical diffuse cerebral pathology may be present in subjects with intermittent temporal slowing, but prospective studies including tests of cognitive function, cerebral perfusion, metabolic status, and advanced neuroimaging should be conducted.

Alternating hemiplegia of childhood and a pathogenic variant of ATP1A3: a case report and pathophysiological considerations.

We describe a case of a child suffering from alternating hemiplegia with a heterozygous p. E815K pathogenic variant of ATP1A3. The patient started to present abnormal eye movements in the first days of life, followed by the appearance at 2 months of dystonic episodes, and later on, by recurrent episodes of alternating hemiplegia more often on the right side. A severe epilepsy started at the age of 2 years with episodes of status epilepticus since the onset which frequently recurred, requiring admission to the intensive care unit. MRI showed bilateral mesial temporal sclerosis and a left-sided ischaemic lesion. Interictal EEG showed bilateral abnormalities, whereas postictal EEG after status epilepticus showed overt slowing on the left side, suggesting a predominant involvement of ictal activity of the left hemisphere. We hypothesize that in our patient, the left hemisphere might have been more prominently affected by the pathogenetic abnormalities underlying alternating hemiplegia of childhood, rendering it more prone to early ischaemic lesions and recurrent unilateral status epilepticus. We speculate whether alternating hemiplegia of childhood shares some common pathophysiological mechanisms with familial hemiplegic migraine that may be associated with a pathogenic variant of ATP1A2.

Pharmacodynamics of remifentanil. Induced intracranial spike activity in mesial temporal lobe epilepsy.

Patients with medically refractory epilepsy may benefit from resective epilepsy surgery. However even the best centers experience surgical failures. It is therefore important to find techniques that may aid in neurosurgical planning of epileptic focus resection. Recordings of electrical brain activity with EEG during seizures reveal abnormal cortical hypersynchronization. Between seizures the EEG often shows interictal depolarizing phenomena such as spikes reflecting an irritable focus of the brain. In the present study we investigated the effect of intravenous remifentanil on the spike activity in the temporal neocortex and hippocampus. We examined 65 patients with mesial temporal lobe epilepsy during surgery, prior to resection. We used a 20-lead grid on the cortex and a 4-lead strip in the lateral ventricle on the hippocampus. At least two 3-min periods of ECoG were recorded - before and after remifentanil injection. In a number of patients we examined the effect of repeated injections in order to estimate the dose-response curve. We describe a significant effect of remifentanil on the average spike activity with an increment from 16 spikes per minute at baseline to 36 spikes per minute after remifentanil injection (p<0.0001). The increase in spike activity was typically seen after 40-50s. When mu-receptors were antagonized with a preceding injection of naloxone, spike activity increased 25% in response to remifentanil as opposed to 80% when remifentanil was preceded by placebo. In only seven out of 59 patients did the injection of remifentanil change the topographic location of the spike focus. Typically administration of remifentanil led to a focus of increased spike count. Activity in other areas was suppressed making the focus stand out from the background. Our observation that remifentanil potentiates spike activity is in agreement with previous findings from smaller studies. Furthermore, we were able to describe the pharmacodynamics of the remifentanil effect on spike activity. Peri-operative provocation with remifentanil may play a future role in guiding neurosurgical intervention during epilepsy resection surgery.

Heart rate variability in infants with West syndrome.

PURPOSE: West syndrome (WS) is a severe age-related acute epileptic encephalopathy of infancy characterized by infantile spasms, hypsarrhythmia and psychomotor delay. The aim of this study was to investigate if patients with WS had an altered autonomic output to the heart. METHODS: In 23 patients with WS the heart rate variability (HRV) was investigated by examining time- and frequency-domain parameters of HRV at the time of the diagnosis of hypsarrhythmia and compared to 22 age-matched controls. For the WS patients the same dataset was obtained and compared again at the end of the study period, when hypsarrhythmia was no longer present. RESULTS: Compared to controls, patients with WS during hypsarrhythmia had significantly lower SDNN (the standard deviation of the NN interval, i.e. the square root of variance) (19.2 ms; p = 0.007, Mann-Whitney's U-Test) and total power (242 ms(2); p = 0.044, Mann-Whitney's U-Test) in the awake state, indicating an abnormal autonomic output to the heart. Comparing the initial to the final examination demonstrated a significant increase in the HRV parameters SDNN (31.3 ms) and total power (757 ms(2); p = 0.001 and p = 0.013, Wilcoxon Signed Ranked Test). In addition, at the final examination the WS-patients no longer differed significantly from the controls. CONCLUSION: Our data suggest that the initial reduction in HRV in patients at the time of onset of WS is transient and related to the presence of hypsarrhythmia.

Danish experience with paediatric epilepsy surgery.

INTRODUCTION: Epilepsy surgery is increasingly used to treat children with medically intractable epilepsy. This study investigates the aetiology and seizure outcome in Danish children operated between 1996 and 2010. METHODS: Retrospectively collected data on structural magnetic resonance imaging (MRI) diagnoses, surgical procedures and seizure outcomes classified according to the Engel Classification were used. Changes over time grouped as 1996-2000, 2001-2005 and 2006-2010 were analysed. RESULTS: A total of 95 children underwent epilepsy surgery. Sixty-three operations were performed in Denmark and 50 abroad. In all, 14 children needed reoperation. The median follow-up period was four years. At the latest follow-up, Engel class I (indicating no disabling seizures) was found in 67% of the patients. Cortical dysplasia, mesial temporal sclerosis and tumour were the most common MRI findings. The percentage of tumours operated decreased over time, and frontal lobe resections increased. In the 2006-2010 period, resections with normal MRI were performed, resulting in a less favourable Engel outcome. Persistent, unexpected complications were seen in three of 113 operations. CONCLUSIONS: The majority of children who undergo epilepsy surgery have a good, worthwhile seizure outcome. The seizure outcome for Danish children corresponds to that of other epilepsy surgery centres. The clinical criteria for selection of patients changed over time. FUNDING: none. TRIAL REGISTRATION: The Danish Data Protection Agency approved the project with record number: 2013-41-2459.

[Epilepsy surgery of Danish children 1996-2002]. / Epilepsikirurgisk behandling af danske børn 1996-2002.

INTRODUCTION: Epilepsy surgery is done in order to obtain seizure freedom or to reduce the number of epileptic seizures in selected patients not responding to medical treatment. Few Danish children have had this treatment, most probably because of some restrictions imposed by The Danish National Health Board. We present the results of the first 22 Danish children who have had epilepsy surgery. MATERIAL AND METHODS: All children up to the age of 15 operated from January 1st 1996 to May 1st 2002 are included. According to the guidelines of The Danish National Health Board, 17 children have been operated abroad because the epileptic focus was extratemporal or intracranial EEG-monitoring was necessary. Follow-up varied from five years and six months to one month. RESULTS: At the time of the operation, all children had a long-lasting medical intractable epilepsy. 18 children had daily seizures and 15 were mentally retarded. Multi-lobar resection was performed in ten, hemispherectomy in three and lobar resection in eight children. Total seizure-free outcome was seen in 12 children, whereas three only had simple partial seizures (totally 68 per cent). The remaining children had at least a 50 per cent seizure reduction. On an average, the cognitive function was unchanged one year after the surgery. The majority of the parents stated that the behaviour of the child had improved on one or more specific issues. One mother stated that to a certain degree she regretted the operation. In four children, an unexpected complication was registered (slight hemiparesis and a hemianopsia). DISCUSSION: The results documented that epilepsy surgery is effective for selected children in spite of long-lasting severe epilepsy. In order to alleviate the consequences of severe epilepsy it is, however, important to refer the patients early. There seems to be a need for more and early referrals for childhood epilepsy surgery in Denmark.

Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study.

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. METHODS: Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. FINDINGS: 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6-9·2) per 1000 patient-years, with a risk of 1·2 (0·6-2·1) per 10,000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. INTERPRETATION: SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time. FUNDING: Commission of European Affairs of the International League Against Epilepsy.

Outcome of accidental hypothermia with or without circulatory arrest: experience from the Danish Præstø Fjord boating accident.

BACKGROUND: Resuscitation guidelines for the treatment of accidental hypothermia are based primarily on isolated cases. Mortality rates are high despite aggressive treatment aimed at restoring spontaneous circulation and normothermia. METHODS: The present report is based on a boating accident where 15 healthy subjects (median age 16 (range 15-45) years) were immersed in 2 °C salt water. Seven victims were recovered in circulatory arrest with a median temperature of 18.4 °C (range 15.5-20.2 °C). They were all rewarmed with extracorporeal membrane oxygenation (ECMO) and were subsequently evaluated with advanced neuroradiological and functional testing. The remaining 7 had established spontaneous circulation without the use of ECMO. One victim drowned in the accident. RESULTS: The victims that survived the accident without circulatory arrest were predominantly females with a higher body mass index. Victims with circulatory arrest pH on arrival was a median of 6.61 (range 6.43-6.94), with ECMO being established a median of 226 (178-241)min after the accident. Magnetic resonance spectroscopy showed neuronal dysfunction in five. In five victims initial normal white matter spectra progressed to show evidence of abnormal axonal membranes. Based on the seven-level Functional Independence Measure test functional outcome was good in six circulatory arrest victims and in all without circulatory arrest. Mild to moderate cognitive dysfunction was seen in six and severe dysfunction in one circulatory arrest victim. CONCLUSION: Seven patients with profound accidental hypothermic circulatory arrest were successfully resuscitated using a management approach that included extracorporeal rewarming, followed by successive periods of therapeutic hypothermia and sedated normothermia and intensive neurorehabilitation. Seven other hypothermic victims (core temperature as low as 23 °C) that did not suffer circulatory arrest also survived the accident.

Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity.

INTRODUCTION: High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patients with low RAS activity. MATERIALS AND METHODS: Nine patients with type 1 diabetes and high and nine with low RAS activity were subjected to hypoglycaemia and euglycaemia in a cross-over study using an intravenous insulin infusion protocol. Cognitive function, electroencephalography, auditory evoked potentials and hypoglycaemic symptoms were recorded. RESULTS: At a hypoglycaemic nadir of 2.2 (SD 0.3) mmol/L the high RAS group displayed significant deterioration in cognitive performance during hypoglycaemia in the three most complex reaction time tasks. In the low RAS group, hypoglycaemia led to cognitive dysfunction in only one reaction time task. The high RAS group reported lower symptom scores during hypoglycaemia than the low RAS group, suggesting poorer hypoglycaemia awareness. CONCLUSION: High RAS activity is associated with increased cognitive dysfunction and blunted symptoms during mild hypoglycaemia compared to low RAS activity. This may explain why high RAS activity is a risk factor for severe hypoglycaemia in type 1 diabetes.

The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease.

Laboratory markers have a prominent place among the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). Here we investigate the capability of protein 14-3-3, total-tau (t-tau), threonin-181-phosphorylated tau (p-tau), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) together with the prion protein gene genotype to discriminate patients with sCJD (n=21) from neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p-tau/t-tau ratio was the best single marker for sCJD with 90% specificity against neurological controls at 86% sensitivity whilst NSE was the least accurate with 79% sensitivity at 90% specificity. Many of the sCJD patients had extremely elevated t-tau values but normal values of the AD-marker p-tau. Protein 14-3-3 was very sensitive (95%) although the specificity was relatively low (75%). A combination of elevated t-tau concentration with the presence of 14-3-3 protein in CSF gave the best test specificity of 96% at 84% sensitivity. We conclude that the combination of more than one CSF marker for neurodegeneration can improve the diagnostic test accuracy for sCJD against neurological controls including patients with other dementias.

Nonconvulsive status epilepticus after electroconvulsive therapy.

SUMMARY: We describe three cases of nonconvulsive status epilepticus induced by electroconvulsive therapy (ECT). Nonconvulsive status epilepticus is an important differential diagnosis in patients who develop prolonged confusion after ECT. The present cases exemplify the difficulty in defining the diagnosis on the basis of the clinical manifestations. The application of electroencephalography is recommended in monitoring patients with prolonged confusion following ECT. Concurrent drug therapy and ECT is discussed.