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BACKGROUND: Juvenile myoclonic epilepsy (JME) is associated with cortical thinning of the motor areas. The relative contribution of antiseizure medication to cortical thickness is unknown. We aimed to investigate how valproate influences the cortical morphology of JME. METHODS: In this cross-sectional study, individuals with JME with and without valproate, with temporal lobe epilepsy (TLE) with valproate and controls were selected through propensity score matching. Participants underwent T1-weighted brain imaging and vertex-wise calculation of cortical thickness. RESULTS: We matched 36 individuals with JME on valproate with 36 individuals with JME without valproate, 36 controls and 19 individuals with TLE on valproate. JME on valproate showed thinning of the precentral gyri (left and right, p<0.001) compared with controls and thinning of the left precentral gyrus when compared with JME not on valproate (p<0.01) or to TLE on valproate (p<0.001). Valproate dose correlated negatively with the thickness of the precentral gyri, postcentral gyri and superior frontal gyrus in JME (left and right p<0.0001), but not in TLE. CONCLUSIONS: Valproate was associated with JME-specific and dose-dependent thinning of the cortical motor regions. This suggests that valproate is a key modulator of cortical morphology in JME, an effect that may underlie its high efficacy in this syndrome.
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Psychosis of epileptic origin can present a wide range of cognitive and affective symptoms and is often underrecognized. Usually occurring in the inter- and postictal phase, epileptic psychosis is mostly related to temporal lobe epilepsy. Here, we describe the clinical presentation and diagnostic workup including routine EEG recording and brain MRI of a 63-year-old woman expressing isolated nihilistic delusions comprising belief of being dead and denial of self-existence. EEG showed an ictal pattern fulfilling the Salzburg criteria of nonconvulsive status epilepticus and brain MRI revealed extensive peri-ictal hyperperfusion. Delusional symptoms and EEG abnormalities subsided after acute antiseizure treatment. Our case illustrates how nihilistic delusions can occur as a direct clinical correlate of seizure activity, thereby expanding the spectrum of ictal neuropsychiatric phenomena in temporal lobe epilepsy and highlighting the need to consider an epileptic origin in patients presenting with psychotic symptoms.
Subject(s)
Delusions , Electroencephalography , Status Epilepticus , Humans , Status Epilepticus/physiopathology , Status Epilepticus/etiology , Female , Delusions/etiology , Delusions/physiopathology , Middle Aged , Magnetic Resonance Imaging , Psychotic Disorders/physiopathology , Psychotic Disorders/etiology , Anticonvulsants/therapeutic useABSTRACT
OBJECTIVE: Perception and recognition of emotions are fundamental prerequisites of human life. Patients with juvenile myoclonic epilepsy (JME) may have emotional and behavioral impairments that might influence socially desirable interactions. We aimed to investigate perception and recognition of emotions in patients with JME by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). METHODS: Sixty-five patients with JME (median age = 27 years, interquartile range [IQR] = 23-34) were prospectively recruited at the Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria. Patients were compared to 68 healthy controls (median age = 24 years, IQR = 21-31), matched for sex, age, and education. All study participants underwent the Networks of Emotion Processing test battery (NEmo), an fMRI paradigm of "dynamic fearful faces," a structured interview for psychiatric and personality disorders, and comprehensive neuropsychological testing. RESULTS: JME patients versus healthy controls demonstrated significant deficits in emotion recognition in facial and verbal tasks of all emotions, especially fear. fMRI revealed decreased amygdala activation in JME patients as compared to healthy controls. Patients were at a higher risk of experiencing psychiatric disorders as compared to healthy controls. Cognitive evaluation revealed impaired attentional and executive functioning, namely psychomotor speed, tonic alertness, divided attention, mental flexibility, and inhibition of automated reactions. Duration of epilepsy correlated negatively with parallel prosodic and facial emotion recognition in NEmo. Deficits in emotion recognition were not associated with psychiatric comorbidities, impaired attention and executive functions, types of seizures, and treatment. SIGNIFICANCE: This prospective study demonstrated that as compared to healthy subjects, patients with JME had significant deficits in recognition and perception of emotions as shown by neuropsychological tests and fMRI. The results of this study may have importance for psychological/psychotherapeutic interventions in the management of patients with JME.
Subject(s)
Myoclonic Epilepsy, Juvenile , Humans , Adult , Young Adult , Prospective Studies , Executive Function , Neuropsychological Tests , Emotions , PerceptionABSTRACT
Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME. Methods: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/). Findings: Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73). Interpretation: We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools. Funding: MING fonds.
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Objective: According to Panksepp's hierarchical emotion model, emotion processing relies on three functionally and neuroanatomically distinct levels. These levels comprise subcortical networks (primary level), the limbic system (secondary level), and the neocortex (tertiary level) and are suggested to serve differential emotional processing. We aimed to validate and extend previous evidence of discrete and dimensional emotion processing in patient with juvenile myoclonic epilepsy (JME). Methods: We recorded brain activity of patients with JME and healthy controls in response to lexical decisions to words reflecting the discrete emotion fear and the affective dimension negativity previously suggested to rely on different brain regions and to reflect different levels of processing. In all study participants, we tested verbal cognitive functions, as well as the relationship of psychiatric conditions, seizure types and duration of epilepsy and emotional word processing. Results: In support of the hierarchical emotion model, we found an interaction of discrete emotion and affective dimensional processing in the right amygdala likely to reflect secondary level processing. Brain activity related to affective dimensional processing was found in the right inferior frontal gyrus and is suggested to reflect tertiary level processing. Psychiatric conditions, type of seizure nor mono- vs. polytherapy and duration of epilepsy within patients did not have any effect on the processing of emotional words. In addition, no differences in brain activity or response times between patients and controls were observed, despite neuropsychological testing revealed slightly decreased verbal intelligence, verbal fluency and reading speed in patients with JME. Significance: These results were interpreted to be in line with the hierarchical emotion model and to highlight the amygdala's role in processing biologically relevant stimuli, as well as to suggest a semantic foundation of affective dimensional processing in prefrontal cortex. A lack of differences in brain activity of patients with JME and healthy controls in response to the emotional content of words could point to unaffected implicit emotion processing in patients with JME.
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OBJECTIVE: We investigated whether the COVID-19 pandemic has affected the clinical characteristics of patients with functional seizure (FS) (at the time of diagnosis) in a large multicenter international study. METHODS: This was a retrospective study. We investigated all patients with FS, who were admitted at the epilepsy monitoring units at six centers in the world: 1. Shiraz, Iran; 2. Salzburg, Austria; 3. Nancy, France; 4. Atlanta, USA; 5. Kuwait City, Kuwait; and 6. Cairo, Egypt. Patients were studied during two time periods: admitted in 2018-2019 (pre-COVID era) and 2020-2021 (COVID era). RESULTS: Three hundred and twenty-six patients were studied. Two hundred and twenty-four (68.7%) patients were diagnosed before and 102 (31.3%) persons during the COVID-19 pandemic. Only, a history of family dysfunction was significantly associated with the COVID-19 pandemic era (Odds Ratio: 1.925, 95% Confidence Interval: 1.099-3.371; pâ¯=â¯0.022). A low level of education might also be associated with FS during the COVID-19 pandemic, at least in some cultures (e.g., the Middle-East). CONCLUSION: The COVID-19 pandemic has not affected the clinical characteristics of patients with FS (at the time of diagnosis). However, a history of family dysfunction was significantly more frequently associated with FS during the COVID-19 pandemic. Multiagency integration of law enforcement responses, social services, and social awareness is recommended to address family dysfunction and domestic violence and support the victims during this pandemic.
Subject(s)
COVID-19 , Pandemics , Humans , Retrospective Studies , SARS-CoV-2 , Seizures/epidemiologyABSTRACT
Several emergencies were admitted less frequently to the hospital during the coronavirus disease 2019 (COVID-19) pandemic. To investigate whether this also occurred with status epilepticus (SE) we compared admissions due to first SE from March to April 2020 ("Time of COVID," TOC) with January to February 2020 ("pre-COVID," preCOV). We also compared admission numbers in TOC and preCOV with the respective 2-month periods in 2018 and 2019 in a retrospective cohort analysis. Two investigators independently searched the hospital patient database for various forms of SE. There was no significant change in the 2-month incidences of first SE in the city of Salzburg from preCOV of 6.1 (95% confidence interval [CI] 2.9-12.3) to TOC of 6.9/100 000 adults (95% CI 3.4-13.3). Admission numbers did not differ significantly from previous years. Estimated adjusted incidence was in line with a recent 5-year epidemiological study in Salzburg. However, a trend toward less-frequent nonconvulsive SE (NCSE) and loss of female predominance were indirect hints of underdiagnosing SE. In contrast to other medical conditions, SE most often presents clinically with impaired consciousness, which may promote admission to emergency departments even in times of lock-down. Further research of medical support of women and patients with NCSE during pandemic-related restrictions is warranted.
Subject(s)
COVID-19 , Hospitalization/statistics & numerical data , Status Epilepticus/epidemiology , Adult , Aged , Aged, 80 and over , Austria , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Young AdultABSTRACT
OBJECTIVE: In 2015, the International League Against Epilepsy (ILAE) proposed a new definition of status epilepticus (SE): 5 minutes of ongoing seizure activity to diagnose convulsive SE (CSE, ie, bilateral tonic-clonic SE) and 10 minutes for focal SE and absence SE, rather than the earlier criterion of 30 minutes. Based on semiology, several types of SE with prominent motor phenomena at any time (including CSE) were distinguished from those without (ie, nonconvulsive SE, NCSE). We present the first population-based incidence study applying the new 2015 ILAE definition and classification of SE and report the impact of the evolution of semiology and level of consciousness (LOC) on outcome. METHODS: We conducted a retrospective population-based incidence study of all adult patients with SE residing in the city of Salzburg between January 2011 and December 2015. Patients with hypoxic encephalopathy were excluded. SE was defined and classified according to the ILAE 2015. RESULTS: We identified 221 patients with a median age of 69 years (range 20-99 years). The age- and sex-adjusted incidence of a first episode of SE, NCSE, and SE with prominent motor phenomena (including CSE) was 36.1 (95% confidence interval [CI] 26.2-48.5), 12.1 (95% CI 6.8-20.0), and 24.0 (95% CI 16.0-34.5; including CSE 15.8 [95% CI 9.4-24.8]) per 100 000 adults per year, respectively. None of the patients whose SE ended with or consisted of only bilateral tonic-clonic activity died. In all other clinical presentations, case fatality was lower in awake patients (8.2%) compared with patients with impaired consciousness (33%). SIGNIFICANCE: This first population-based study using the ILAE 2015 definition and classification of SE found an increase of incidence of 10% compared to previous definitions. We also provide epidemiologic evidence that different patterns of status evolution and LOCs have strong prognostic implications.
Subject(s)
Population Surveillance , Status Epilepticus/diagnosis , Status Epilepticus/epidemiology , Adult , Aged , Aged, 80 and over , Austria/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Population Surveillance/methods , Retrospective Studies , Status Epilepticus/classification , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: The European Union-funded E-PILEPSY network (now continuing within the European Reference Network for rare and complex epilepsies [EpiCARE]) aims to harmonize and optimize presurgical diagnostic procedures by creating and implementing evidence-based guidelines across Europe. The present study evaluates the current evidence on the diagnostic accuracy of long-term video-electroencephalographic monitoring (LTM) in identifying the epileptogenic zone in epilepsy surgery candidates. METHODS: MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched for relevant articles. First, we used random-effects meta-analytical models to calculate pooled estimates of sensitivity and specificity with respect to postsurgical seizure freedom. In a second phase, we analyzed individual patient data in an exploratory fashion, assessing diagnostic accuracy within lesional and nonlesional temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE) patients. We also evaluated seizure freedom rate in the presence of "localizing" or "nonlocalizing" LTM within each group. The quality of evidence was assessed using the QUADAS-2 tool and the GRADE approach. RESULTS: Ninety-four studies were eligible. Forty-four were included in sensitivity meta-analysis and 34 in specificity meta-analysis. Pooled sensitivity was 0.70 (95% confidence interval [CI] = 0.60-0.80) and specificity was 0.40 (95% CI = 0.27-0.54). Subgroup analysis was based on individual data of 534 patients (41% men). In lesional TLE patients, sensitivity was 0.85 (95% CI = 0.81-0.89) and specificity was -0.19 (95% CI = 0.13-0.28). In lesional ETLE patients, a sensitivity of 0.47 (95% CI = 0.36-0.58) and specificity of 0.35 (95% CI = 0.21-0.53) were observed. In lesional TLE, if LTM was localizing and concordant with resection site, the seizure freedom rate was 247 of 333 (74%), whereas in lesional ETLE it was 34 of 56 (61%). The quality of evidence was assigned as "very low." SIGNIFICANCE: Long-term video-electroencephalographic monitoring is associated with moderate sensitivity and low specificity in identification of the epileptogenic zone. Sensitivity is remarkably higher in lesional TLE compared to lesional ETLE. Substantial heterogeneity across the studies indicates the need for improved design and quality of reporting.
Subject(s)
Electroencephalography/methods , Epilepsy/diagnosis , Epilepsy/surgery , Neurosurgical Procedures , Humans , Monitoring, Physiologic , Prognosis , Reproducibility of ResultsABSTRACT
Status epilepticus (SE) is among the most common neurological emergencies. In refractory SE, due to subcellular maladaptive changes, γ-aminobutyric acidergic drugs are no longer effective, and there is an increase in synaptic N-methyl-d-aspartate (NMDA) receptors. Ketamine (KET) is a noncompetitive N-methyl-d-aspartate receptor antagonist that could be of value in the treatment of refractory SE. The aim was to analyze all published studies on KET in the treatment of SE. A systematic search (PubMed) of the literature identified 25 studies (from December 1996 to March 2017); with the exception of two prospective studies, all studies were retrospective in nature and published as a full paper. To date, PubMed lists a total number of 244 episodes of SE treated with KET (13 case reports and five case series in adults; four case reports and three case series in children); the overall success rate was 74% (153/207) in adults and 73% (27/37) in children. Adverse events were rare. Current evidence on the use of KET in acute seizures and SE is mostly restricted to retrospective case reports and case series, except for two prospective case series without control (class IV). Further prospective studies to inform clinicians are necessary.
Subject(s)
Anticonvulsants/administration & dosage , Ketamine/administration & dosage , Status Epilepticus/drug therapy , Administration, Intravenous , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , PubMed , Treatment Outcome , Young AdultABSTRACT
In refractory status epilepticus (SE), γ-aminobutyric acidergic drugs become less effective and glutamate plays a major role in seizure perpetuation. Data on the efficacy of perampanel (PER) in treatment of refractory SE in humans are limited. Here, we present a single-center case series of patients with refractory SE who received PER orally in an intensive care unit. We retrospectively analyzed treatment response, outcome, and adverse effects of all patients with refractory SE in our Neurological Intensive Care Unit who received add-on PER between September 2012 and February 2018. Thirty patients with refractory SE (median = 72 years, range = 18-91, 77% women) were included. In 14 patients (47%), a high-dose approach was used, with a median initial dose of 24 mg (range = 16-32). In five patients (17%), SE could be terminated after PER administration (median dose = 6 mg, range = 6-20 mg, 2/5 patients in high-dose group). Clinical response was observed after a median of 24 hours (range = 8-48 hours), whereas electroencephalogram resolved after a median of 60 hours (range = 12-72 hours). Time to treatment response tended to be shorter in patients receiving high-dose PER (median clinical response = 16 hours vs 18 hours; electroencephalographic response = 24 hours vs 72 hours), but groups were too small for statistical analysis. Continuous cardiorespiratory monitoring showed no changes in cardiorespiratory function after "standard" and "high-dose" treatment. Elevated liver enzymes without clinical symptoms were observed after a median of 6 days in seven of 30 patients (23%; 57% high dose vs 43% standard dose), of whom six also received treatment with phenytoin (PHT). Outcome was unfavorable (death, persistent vegetative state) in 13 patients (43%; 39% high dose vs 61% standard dose), and good recovery (no significant disability, moderate disability) was achieved in nine patients (56% high dose vs 44% standard dose). Oral PER in loading doses up to 32 mg were well tolerated but could terminate SE only in a few patients (5/30; 17%). Long duration of SE, route of administration, and severe underlying brain dysfunction might be responsible for the modest result. An intravenous formulation is highly desired to explore the full clinical utility in the treatment of refractory SE.
Subject(s)
Anticonvulsants/therapeutic use , Pyridones/therapeutic use , Status Epilepticus/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Austria , Electroencephalography , Female , Humans , Intensive Care Units , Male , Middle Aged , Nitriles , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
Brivaracetam (BRV) is a high-affinity synaptic vesicle glycoprotein 2A ligand that is structurally related to levetiracetam (LEV). Compared to LEV, its affinity to the ligand is >10%-30% higher. Due to its more lipophilic characteristics, it might have a quicker penetration across the blood-brain barrier and potentially also a stronger anticonvulsant effect. Thus, we aimed to explore its usefulness in the treatment of status epilepticus (SE). We retrospectively assessed treatment response and adverse events in adjunctive treatment with intravenous BRV in patients with SE from January 2016 to July 2017 at our institution. Seven patients aged median 68 years (range = 29-79) were treated with intravenous BRV. Three patients had SE with coma and four without. SE arose de novo in two patients; etiology was remote symptomatic in four patients and progressive symptomatic in one patient. The most frequent etiology was remote vascular in two patients. BRV was administered after median four antiepileptic drugs (range = 2-11). Time of treatment initiation ranged from 0.5 hours to 105 days (median = 10.5 hours). Immediate clinical and electrophysiological improvement was observed in two patients (29%). Median loading dose was 100 mg intravenously over 15 minutes (range = 50-200 mg), titrated up to a median dose of 100 mg/d (range = 100-300). Median Glasgow Outcome Scale score was 3 (range = 3-5), with an improvement in 86% of patients compared to admission. We observed no adverse events regarding cardiorespiratory function. BRV might have potential as a novel antiepileptic drug in early stages of SE. Its potential may lie its ability to cross the blood-brain barrier more quickly than LEV and its favorable safety profile. Prospective studies for the use of BRV in SE are required.
Subject(s)
Anticonvulsants/administration & dosage , Pyrrolidinones/administration & dosage , Status Epilepticus/drug therapy , Treatment Outcome , Administration, Intravenous , Adult , Aged , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Retrospective Studies , Time FactorsABSTRACT
Alterations of interaction (connectivity) of the EEG reflect pathological processes in patients with neurologic disorders. Nevertheless, it is questionable whether these patterns are reliable over time in different measures of interaction and whether this reliability of the measures is the same across different patient populations. In order to address this topic we examined 22 patients with mild cognitive impairment, five patients with subjective cognitive complaints, six patients with right-lateralized temporal lobe epilepsy, seven patients with left lateralized temporal lobe epilepsy, and 20 healthy controls. We calculated 14 measures of interaction from two EEG-recordings separated by 2 weeks. In order to characterize test-retest reliability, we correlated these measures for each group and compared the correlations between measures and between groups. We found that both measures of interaction as well as groups differed from each other in terms of reliability. The strongest correlation coefficients were found for spectrum, coherence, and full frequency directed transfer function (average rho > 0.9). In the delta (2-4 Hz) range, reliability was lower for mild cognitive impairment compared to healthy controls and left lateralized temporal lobe epilepsy. In the beta (13-30 Hz), gamma (31-80 Hz), and high gamma (81-125 Hz) frequency ranges we found decreased reliability in subjective cognitive complaints compared to mild cognitive impairment. In the gamma and high gamma range we found increased reliability in left lateralized temporal lobe epilepsy patients compared to healthy controls. Our results emphasize the importance of documenting reliability of measures of interaction, which may vary considerably between measures, but also between patient populations. We suggest that studies claiming clinical usefulness of measures of interaction should provide information on the reliability of the results. In addition, differences between patient groups in reliability of interactions in the EEG indicate the potential of reliability to serve as a new biomarker for pathological memory decline as well as for epilepsy. While the brain concert of information flow is generally variable, high reliability, and thus, low variability may reflect abnormal firing patterns.
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PURPOSE: The aim of this qualitative study was to determine which perception of personal comfort patients name in the context of their hospitalization in an Austrian Epilepsy Monitoring Unit (EMU). METHODS: Problem-centred interviews with twelve inpatients were conducted. Data analyses were done according to Mayring's qualitative content analyses following the technique of structuring-deductive category assignment. RESULTS: Patients experienced different kinds of comfort along with their hospitalization in the EMU. Comfort-decreasing factors were bed rest, boredom, and waiting for possible seizures. As comfort-increasing factors, hope for enhanced seizure control, support by family and staff, and intelligible information about the necessity of restrictive conditions were identified. CONCLUSIONS: The study results should assist health care professionals, enabling them to design comfort enhancing interventions for patients undergoing video-electroencephalography (EEG) investigations in an EMU. Some of these seem to be simple and obtainable without high financial or technical effort. Others are more complex and have to be further assessed for their feasibility.
Subject(s)
Electroencephalography/methods , Epilepsy/diagnosis , Hospitalization , Seizures/diagnosis , Adult , Austria , Epilepsy/physiopathology , Female , Humans , Male , Middle Aged , Patient Preference , Qualitative Research , Seizures/physiopathologyABSTRACT
Objective: Safety in epilepsy monitoring units (EMUs) has become an increasing concern because adverse events occur in up to 10% of patients undergoing long-term video EEG in EMUs. The aim of this study was to assess the effectiveness of a specific safety protocol in an EMU. Methods: We retrospectively assessed the adverse event rates in a group without (group 1, 84-month period, Innsbruck, Austria) and a group with (group 2, 33-month period, Salzburg, Austria) personalized safety measures utilizing a standardized protocol for long-term epilepsy monitoring in high-risk patients. Differences in adverse event rates during and after long-term video EEG between the two groups were calculated and compared. Results: In group 1, 44/507 (9%, 95% confidence interval [CI] 6.5-11.5%) patients experienced 53 adverse events: 20/507 (4%, 95% CI 2.6-6.0%) patients had psychiatric events, 15/507 (3%, 95% CI 1.8-4.8%) patients sustained a total of 19 injuries during seizures, and 10/507 (2%, 95% CI 1.1-3.6%) patients had 13 episodes of status epilepticus; one adverse event was treatment-related (valproic acid-induced encephalopathy; 1/507, 0.2%, 95% CI 0.0-1.1%). By using the new safety protocol in group 2, the adverse event rate was only 5% (95% CI 3.4-7.6%; 30 adverse events in 26/491; 45% reduction; p = 0.036), in contrast. These events included 13 psychiatric complications in 13/491 (2%, 95% CI 1.6-4.5%, p = 0.252) patients, 12 seizure-related injuries in 9/491 (2%, 95% CI 1.0-3.4%, p = 0.250) patients, and 5 episodes of status epilepticus in 4/491 (1%, 95% CI 0.3-2.1%, p = 0.120) patients. Significance: Implementation of personalized safety measures in high-risk patients resulted in a clinically relevant reduction of adverse events in the EMU. Safety protocols are a valid tool to reduce the occurrence of adverse events in EMUs.
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BACKGROUND: The aim of this study was to analyse registry data of seizure outcome and adverse events (AEs) for perampanel as add-on therapy in patients with focal epilepsy since its approval in 2012 for adjunctive treatment of focal epilepsy in patients ⩾12 years. METHOD: A retrospective 2-year chart review of all patients receiving perampanel was carried out. RESULTS: A total of 122 patients received perampanel [median treatment length: 20.1 (range: 3.4-26.8) months]; 71 (58%) remained on treatment at last follow up. Overall, 33 patients (27%) were seizure-free for ⩾3 months at last follow up; of these, eight were seizure free for ⩾3 times the longest interictal interval before perampanel therapy; 18 (15%) had reduced seizure frequency ⩾50%. A total of 58 (47%) had an AE and 34 (28%) withdrew from treatment because of AEs. AEs included dizziness (33%), fatigue (12%), psychiatric symptoms (8%), cognitive deficits (7%), speech problems (5%), nausea (4%) and gait problems (4%). AEs subsided in 17/18 patients (94%) following a 2 mg dose reduction. A total of 43 (35%) took a concomitant enzyme inducer. Patients not taking enzyme inducers were more likely to be seizure free (p = 0.002); there were no other between-group differences. CONCLUSIONS: Perampanel was well tolerated and improved seizure control in 42% of patients (50- 100% reduction), with higher rates in those not receiving a concomitant enzyme inducer. AEs, particularly dizziness, were common but often disappeared with a slight dose reduction. The results are consistent with those from randomized controlled trials.
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PURPOSE: Status epilepticus (SE) is one of the most common neurological emergencies with a high incidence in the elderly. Major determinants of prognosis are patients' age, duration of SE and underlying etiology. We aimed identifying differences in clinical presentation of SE, etiologies and outcome between patients (pts.) sixty years or older (≥60) and younger than sixty (<60) years (yrs). METHODS: We retrospectively analyzed 120 patients (48 women) with SE admitted to the Neurological Intensive Care Unit (NICU), Department of Neurology, Paracelsus Medical University Salzburg, Austria between 1/2011 and 01/2013. KEY FINDINGS: Median age was 69 years (range 14-90) (63% ≥60yrs). Generalized tonic clonic SE was the most common SE type, whereas non convulsive SE with and without coma tended to occur more frequently in the elderly (33% ≥60 yrs. vs. 20%<60 yrs, Chi2=3.511, p=0.061). Preexisting history of epilepsy was more common in the younger age group (64% vs 41% p=0.014). An acute symptomatic cause of SE was identified in 25% (31/120), with cerebrovascular diseases being more frequent in the elderly (47% vs. 11%; p<0.01). Duration of SE did not differ between the age groups (p=0.63). Mortality was higher in elderly patients (31% vs. 7%, p=0.028, Chi Square=5.18) and moderate disability in younger patients (42% vs 17%; p=0.005, Chi Square=7.83). After Bonferroni correction only the higher rate of cerebrovascular etiologies in the elderly was statistically significant. SIGNIFICANCE: In the elder population, SE occurs more often in patients without preexisting epilepsy and is most frequently caused by cerebrovascular diseases. NCSE tends to be more frequent in the elderly and diagnosis is complicated by subtle clinical presentation. Even though comorbidities represent treatment limitations, in our sample no differences in choice of AED as well as dosage were observed between the age groups, reflecting a trend toward AEDs with more favorable adverse event profile in all patients. SE in older patients is associated with poorer outcome and higher mortality.
Subject(s)
Status Epilepticus/epidemiology , Status Epilepticus/etiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Anticonvulsants , Comorbidity , Critical Care , Epilepsy/complications , Epilepsy/epidemiology , Epilepsy/therapy , Female , Humans , Incidence , Length of Stay , Male , Middle Aged , Retrospective Studies , Status Epilepticus/therapy , Young AdultABSTRACT
BACKGROUND: Several EEG criteria have been proposed for diagnosis of non-convulsive status epilepticus (NCSE), but none have been clinically validated. We aimed to assess the diagnostic accuracy of the EEG criteria proposed by a panel of experts at the fourth London-Innsbruck Colloquium on Status Epilepticus in Salzburg, 2013 (henceforth called the Salzburg criteria). METHODS: We did a retrospective, diagnostic accuracy study using EEG recordings from patients admitted for neurological symptoms or signs to three centres in two countries (Danish Epilepsy Centre, Dianalund, Denmark; Aarhus University Hospital, Aarhus, Denmark; and Paracelsus Medical University, Salzburg, Austria). Participants were included from the Danish centres if they were aged 4 months or older, and from the Austrian centre if aged 18 years or older. Participants were sorted into two groups: consecutive patients under clinical suspicion of having NCSE (the clinical validation group) or consecutive patients with abnormal EEG findings but no clinical suspicion of NCSE (the control group). Two raters blinded to all other patient data retrospectively analysed the EEG recordings and, using the Salzburg criteria, categorised patients as in NCSE or not in NCSE. By comparing with a reference standard inferred from all clinical and para-clinical data, therapeutic response, and the final outcome, we calculated sensitivity, specificity, overall diagnostic accuracy, positive and negative predictive values, and inter-rater agreement for the Salzburg criteria. The reference standard was inferred by two raters who were blinded to the scorings of the Salzburg criteria. FINDINGS: We retrospectively reviewed EEG data from 220 patients. EEGs in the clinical validation group were recorded in 120 patients between Jan 1, and Feb 28, 2014 (Austria), and Aug 1, 2014, and Jan 31, 2015 (Denmark). EEGs in the control group were recorded in 100 patients between Jan 13 and Jan 22, 2014 (Austria) and Jan 12 and Jan 26, 2015 (Denmark). According to the reference standard, 43 (36%) of the 120 patients in the validation group had NCSE. In the validation cohort sensitivity was 97·7% (95% CI 87·9-99·6) and specificity was 89·6% (80·8-94·6); overall accuracy was 92·5% (88·3-97·5). Positive predictive value was 84·0% (95% CI 74·1-91·5) and negative predictive value was 98·6% (94·4-100). Three people in the control group (n=100) fulfilled the Salzburg criteria and were therefore false positives (specificity 97·0%, 95% CI 91·5-99·0; sensitivity not calculable). Inter-rater agreement was high for both the Salzburg criteria (k=0·87) and for the reference standard (k=0·95). Therapeutic changes occurred significantly more often in the group of patients fulfilling Salzburg criteria (42 [84%] of 50 patients) than in those who did not (11 [16%] of 70; p<0·0001). INTERPRETATION: The Salzburg criteria for diagnosis of NCSE have high diagnostic accuracy and excellent inter-rater agreement, making them suitable for implementation in clinical practice. FUNDING: None.
Subject(s)
Electroencephalography/standards , Practice Guidelines as Topic/standards , Status Epilepticus/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Young AdultABSTRACT
OBJECTIVE: The aim was to describe the safety and efficacy of (S)-ketamine [(S)-KET] in a series of patients with refractory and super-refractory status epilepticus (RSE and SRSE) in a specialized neurological intensive care unit (NICU). METHODS: We retrospectively analyzed the data of patients with RSE and SRSE treated with (S)-KET in the NICU, Salzburg, Austria, from 2011 to 2015. Data collection included demographic features, clinical presentation, diagnosis, electroencephalogram (EEG) data, anticonvulsant treatment, timing, and duration of treatment with (S)-KET. Outcomes were seizure control and death. RESULTS: A total of 42 patients (14 women) with RSE and SRSE were treated with (S)-KET. The median duration of status epilepticus (SE) was 10 days [first quartile (Q1) 5.0, Q3 21.0]; the median latency from SE onset to the first administration of (S)-KET was 3 days (Q1 2.0, Q3 6.8). Prior to (S)-KET administration, patients had received a median of two (Q1 2.0, Q3 3.0) anesthetics and three (Q1 2.0, Q3 4.0) antiepileptic drugs. Forty percent of patients (17/42) received propofol: 65 % prior to (S)-KET; 35 % at the same time with (S)-KET. Seven patients received a median bolus of (S)-KET of 200 mg (Q1 200, Q3 250) followed by a continuous infusion, while 35 started with a continuous infusion (maximum rate median 2.55 mg/kg/h; Q1 2.09, Q3 3.22). In 64 % of patients (27/42), (S)-KET was the last drug before SE cessation; in five patients, it was given with propofol at the same time. Median duration of administration was 4 days (Q1 2.0, Q3 6.8). Overall (S)-KET treatment was well tolerated, adverse effects were not observed, and overall mortality was 45.2 %. CONCLUSIONS: Treatment of SRSE in adult patients with (S)-KET led to resolution of status in 64 %. No adverse events were found, indicating a favorable safety profile.
Subject(s)
Drug Resistant Epilepsy/drug therapy , Excitatory Amino Acid Antagonists/administration & dosage , Ketamine/administration & dosage , Status Epilepticus/drug therapy , Aged , Anesthetics/administration & dosage , Anticonvulsants/administration & dosage , Electroencephalography , Excitatory Amino Acid Antagonists/adverse effects , Female , Humans , Intensive Care Units , Ketamine/adverse effects , Male , Middle Aged , Propofol/administration & dosage , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: The non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) - receptor antagonist perampanel (PER) was approved in 2015 for treatment of primary generalized tonic-clonic seizures (pGTCS). The aim of this narrative review is to summarize available data on pharmacological properties, efficacy and tolerability of PER in pGTCs. AREAS COVERED: Data sources included MEDLINE, EMBASE, Google Scholar and ClinicalTrials.gov, conference proceedings of the ILAE congresses and the most recent conference proceedings of the American Epilepsy Society (2013 to 2015). EXPERT OPINION: A placebo-controlled clinical phase III study including 164 patients (≥ 12 years) with pGTCS in idiopathic generalized epilepsies (IGE) demonstrated efficacy of PER in reducing pGTCS with good tolerability profile, and without aggravating absence seizures or myoclonic seizures. Dizziness, the main adverse event (AE), can be avoided by bedtime administration. Psychiatric AEs ranging from mild depression to aggression and suicidal attempts should be especially monitored in patients with a history of psychiatric disorders. Co-administration of enzyme inducing antiepileptic drugs (AEDs) might decrease PER plasma levels and make dose adjustment necessary. A reduced efficacy of progesterone-containing oral contraceptives should be considered when administering PER to young women. There is lack of evidence on PER treatment in pregnancy. Although no teratogenic effects were observed in animal models, PER is not recommended for women of childbearing age without contraception.