Treating status epilepticus in adults. / Behandling av status epilepticus hos voksne.

This clinical review examines the treatment of status epilepticus, a condition in which epileptic seizures are prolonged and pose a significant risk of brain damage and death. International guidelines recommend the use of benzodiazepines as first-line treatment, and these should be administered promptly and in appropriate doses. Second-line treatment involves the use of high-dose anti-seizure medications to stop and prevent seizures. If seizure activity persists, general anaesthesia should be administered as soon as possible. All neurological hospital departments should have established and rehearsed protocols for treating status epilepticus.

Cognition in adult patients with newly diagnosed non-lesional temporal lobe epilepsy.

OBJECTIVE: To evaluate whether cognitive performance is affected in newly diagnosed temporal lobe epilepsy (TLE) and to determine the most vulnerable cognitive domains. METHODS: In this baseline longitudinal study, differences in memory and non-memory cognitive functions were assessed using comprehensive neuropsychological test batteries in 21 adult patients with newly diagnosed non-lesional TLE and individually matched controls. In addition, the analyses included ratings of self-perceived emotional status. RESULTS: The patients performed more poorly than the control group regarding delayed visual memory (p = 0.013) and executive function tasks related to switching (Trail Making Test and verbal fluency shifting; p = 0.025 and p = 0.03, respectively). We found no differences in verbal learning and memory, attention/working memory/processing speed, and other executive functions. SIGNIFICANCE: Our results show that patients with TLE often have specific cognitive deficits at time of diagnosis, even in the absence of structural brain abnormalities. This supports the hypothesis that memory dysfunction is linked to an underlying pathology rather than to the effect of recurrent seizures, long-term use of anti-seizure medication, or other epilepsy-related factors. As certain executive functions are affected at an early stage, the pathology may involve brain regions beyond the temporal lobe and may comprise larger brain networks. These results indicate the need for greater awareness of cognition at the time of diagnosis of TLE and before initiation of treatment, and integration of neuropsychological assessment into early routine clinical care.

Influence of valproate-induced hyperammonemia on treatment decision in an adult status epilepticus cohort.

INTRODUCTION: Status epilepticus (SE) is a neurological emergency in which immediate intervention is required to prevent permanent brain damage and death. Intravenous (IV) valproic acid (VPA) is often used for the treatment of SE. However, IV VPA frequently increases the blood ammonia level. In this study, we explore the impact of IV VPA-induced hyperammonemia (HA) on treatment management of SE and discuss the challenges related to this particular condition. METHODS: We used data from medical records of 31 adult patients (≥18 years) treated with IV VPA for SE at Oslo University Hospital between January 2006 and October 2019. Clinical and blood sample data and information about the influence of HA on treatment were collected. Correlations between ammonia levels and other continuous or categorical variables were tested using the Pearson's correlation coefficient. The Kruskal-Wallis H-test was used to analyze associations between different variables and treatment decisions. RESULTS: Thirty of 31 patients had increased ammonia level during IV VPA treatment. In 16/30 patients, VPA was discontinued, and in 6/30 patients, the dose was reduced. We found a difference in the median peak ammonia level among the groups where VPA was discontinued (99 µmol/l), reduced (71 µmol/l), and continued (55.5 µmol/l) (P = 0.008). Also clinical status, measured by West Haven Criteria, varied among the groups where VPA was discontinued (3.5), reduced (2.5), and continued (2.0) (P = 0.01). Treatment decisions at peak ammonia were not associated with the level of liver enzymes and bilirubin. CONCLUSION: Hyperammonemia had a substantial impact on further management. To date, no recommendations exist on how to manage VPA-induced HA in SE. We call for systematic prospective studies and evidence-based guidelines.

Episodic Memory Dysfunction and Effective Connectivity in Adult Patients With Newly Diagnosed Nonlesional Temporal Lobe Epilepsy.

OBJECTIVE: Epilepsy is associated with both changes in brain connectivity and memory function, usually studied in the chronic patients. The aim of this study was to explore the presence of connectivity alterations measured by EEG in the parietofrontal network in patients with temporal lobe epilepsy (TLE), and to examine episodic memory, at the time point of diagnosis. METHODS: The parietofrontal network of newly diagnosed patients with TLE (N = 21) was assessed through electroencephalography (EEG) effective connectivity and compared with that of matched controls (N = 21). Furthermore, we assessed phenomenological aspects of episodic memory in both groups. Association between effective connectivity and episodic memory were assessed through correlation. RESULTS: Patients with TLE displayed decreased episodic (p ≤ 0.001, t = -5.18) memory scores compared with controls at the time point of diagnosis. The patients showed a decreased right parietofrontal connectivity (p = 0.03, F = 4.94) compared with controls, and significantly weaker connectivity in their right compared with their left hemisphere (p = 0.008, t = -2.93). There were no significant associations between effective connectivity and episodic memory scores. CONCLUSIONS: We found changes in both memory function and connectivity at the time point of diagnosis, supporting the notion that TLE involves complex memory functions and brain networks beyond the seizure focus to strongly interconnected brain regions, already early in the disease course. Whether the observed connectivity changes can be interpreted as functionally important to the alterations in memory function, it remains speculative.

Predictive performances of STESS and EMSE in a Norwegian adult status epilepticus cohort.

PURPOSE: "Status Epilepticus Severity Score" (STESS) and "Epidemiology-based Mortality Score in Status Epilepticus" (EMSE) are two clinical scoring systems aiming to predict mortality in status epilepticus (SE). The objective of this study was to compare their predictive performances in a cohort of 151 SE-patients from Oslo University Hospital in the period 2001-2017. METHOD: Variables used to calculate STESS (age, previous seizures, worst SE-semiology, level of consciousness) and two different versions of EMSE, EMSE-EAC (etiology, age, comorbidities) and EMSE-EACE (etiology, age, comorbidities, EEG-pattern), as well as outcome were collected retrospectively. Receiver Operating Characteristic (ROC)-analyses, determination of best cut-off values, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were performed. In addition, Precision-Recall curves (PRC) were produced, plotting PPV as a function of Se. RESULTS: Thirteen patients (9%) died during their hospital stay. STESS did not accurately predict mortality, with a ROC-curve showing an area under the curve (AUC) of 0.625(95%CI = 0.472-0.783), p = 0.15. EMSE-EAC performed better with an AUC of 0.714(95%CI = 0.552-0.873), p = 0.01 and a best cut-off value of 37. Se was 69.2%, Sp 72.1%, PPV 19% and NPV 96.2%. EMSE-EACE performed best with an AUC of 0.855(95%CI = 0.736-0.976), p < 0.0005 and a best cut-off value of 79. Se was 77.8%, Sp 87.8%, PPV 36.8% and NPV 97.7%. The PRC showed areas under the PRC of 0.23 for EMSE-EAC and 0.46 for EMSE-EACE. CONCLUSIONS: EMSE-EAC and EMSE-EACE performed better than STESS and may be useful in identifying the patients at risk of death in SE. PRC may give a more relevant visual representation of predictive utility than ROC-curves in situations of imbalanced datasets.

Factors associated with refractoriness and outcome in an adult status epilepticus cohort.

PURPOSE: Several multinational prospective registers have shown that a significant proportion of status epilepticus (SE) patients are not treated in line with international guidelines. The aim of this study was to assess quality of treatment and to identify factors associated with refractoriness and outcome in a cohort of adult SE patients in Norway. METHODS: 151 patients treated in Oslo University Hospital from 2001 to 2017 were included. One SE-episode was selected per patient and variables related to the patient, SE-episode, treatment and outcome entered into a database. Status Epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in SE (EMSE) were calculated for each episode. RESULTS: 68% (n = 102) of SE-episodes were responsive, 20% (n = 30) refractory and 12% (n = 19) superrefractory. Mortality was 9%, with a significant difference between responsive episodes (1%) and refractory (superrefractory included) episodes (24%), p < 0.001. 86% of patients received a benzodiazepine as 1st antiepileptic drug. Multivariate analysis showed that non-convulsive SE in coma was significantly associated with refractoriness (p = 0.04), while focal non-convulsive SE without coma was associated with responsiveness (p = 0.03). Younger age was associated with superrefractoriness (p = 0.02). Regarding outcome, EMSE-EtiologyAgeComorbiditiesEEG (EACE)≥64 (p = 0.02) and use of vasopressors (p = 0.03) were associated with a worsening of the modified Rankin scale at discharge. STESS was only associated with outcome in univariate analysis. CONCLUSION: In this cohort in which international guidelines for treatment of SE were well followed, semiology of the SE was found to be the most important determinant of refractoriness, and the new clinical scoring system EMSE-EACE was robustly associated with outcome.

Seizure-like episodes and EEG abnormalities in patients with long QT syndrome.

PURPOSE: The congenital long QT-syndrome (cLQTS) is characterized by ventricular arrhythmias, syncope and sudden cardiac death. Many LQTS genes are also expressed in the brain and emerging evidence suggest that cardiac channelopathies can also cause epilepsy. The aim of the study is to explore evidence of epilepsy and/or EEG abnormalities in a cohort with a genotyped diagnosis of LQT1 or LQT2. METHODS: Adult patients were randomly selected from the outpatient clinic and a random sample of healthy controls were recruited from the general population. Ictal semiology was explored in symptomatic patients. A 1 h 64-channel awake EEG was performed and analyzed by visual assessment. Brain connectivity was quantified by Directed Transfer Function (DTF) from the current source density estimate within the theta band (4-7 Hz). RESULTS: Fifteen patients with LQT1, 20 with LQT2 and 20 controls were included. Seventy-one % of the patients reported loss of consciousness (LOC); 44% in combination with convulsions. EEG was abnormal in 34% of patients and 10% of controls (p < 0.05). Two patients had epileptiform or sharp activity. The fronto-parietal DTF connectivity was significantly altered in patients compared to controls (LQT1 p = 2.2 × 10-6, LQT2 p = 0.044). CONCLUSION: Seizure-like episodes and EEG abnormalities were common in our cohort with cLQTS patients. However, we could not find firm evidence of epilepsy. Our findings reinforce the notion that cLQTS is a cardiocerebral channelopathy. Correct classification of seizures may be challenging to the clinician, but of vital importance for patients.

Clinical and psychosocial follow-up study of children treated with extracorporeal membrane oxygenation.

BACKGROUND: Serious heart and pulmonary failure may be treated with extracorporeal membrane oxygenation (ECMO). The aim of this follow-up study was a multimodal assessment of outcome in children surviving ECMO at our hospital from 1991 to 2004. METHODS: Twenty-two children were, on average, 1.18 years old (SD = 1.92; range, 0.1 to 7.8) when ECMO was initiated. Average age at follow-up was 7.2 years (range, 1.8 to 13.9). Thirteen children were treated for cardiac and nine for pulmonary failure. Venoarterial ECMO was performed in 21 patients and venovenous ECMO in one patient. The protocol included a review of patients records, clinical, neurologic and neuropsychologic, and radiological examinations, electroencephalogram, and interviews with the parents. RESULTS: Moderate or severe impairment in at least two clinical assessments were found in 16 (72.7%) children. Five (22.7%) children had cerebral palsy and 15 (68.2%) had moderate or severe cognitive impairment. Eight (36%) children had pathological radiologic findings. Pathological electroencephalograms were found in 11 (50%) patients including four (18.2%) with epileptic activity. Children with radiologic findings had a slightly worse cognitive outcome. There was no association between the neurophysiologic findings and the neuropsychologic performance or the radiologic findings. Based on parental assessment, only four children had pathological scores. CONCLUSIONS: All children, except for two, came walking to the follow-up visit. All parents were positive to the ECMO treatment, and reported a good or slightly reduced quality of life for their child. Cerebral sequelae were frequently found in children treated with ECMO. The need for treatment and support should be assessed in order to optimize their physical and psychosocial functioning.