1,721,004 research outputs found
Biomarcatori sierici, liquorali e neuroradiologici per la diagnosi e la prognosi in pazienti adulti con Stato Epilettico
No full textLo Stato Epilettico (SE) è una frequente emergenza neurologica caratterizzata da elevata morbidità e mortalità nel breve termine. Biomarcatori prognostici e diagnostici possono aiutare nella valutazione e nella gestione di questi pazienti. Un approccio multimodale, che aggiunga, a fianco della valutazione clinico-elettroencefalografica, la misurazione di biomarcatori neuroradiologici e di danno neuro-gliale può permettere di migliorare l’identificazione di coloro che svilupperanno sequele a breve e lungo termine ed assistere la diagnosi, specialmente nei casi più dubbi. Scopi dello studio: 1. Determinare i patterns perfusionali di CT (CTP) dello SE e definirne il ruolo diagnostico nei casi di SE non convulsivo (NCSE); 2. Definire i livelli sierici e liquorali di biomarcatori di danno neuro-gliale e valutarne il ruolo prognostico; 3. Definire l’utilità di un approccio multimodale nella diagnosi e prognosticazione dello SE.
I pazienti arruolati sono stati sottoposti a prelievo sierico durante lo SE, entro 72 ore dalla sua diagnosi per la misurazione di Neurofilamenti a catena leggera (NfL) e di proteina S100B. Gli stessi biomarcatori sono stati misurati nei gruppi di controllo: controlli sani (HC) e pazienti con diagnosi di epilessia (EP) omogenei per età e genere. Le misure di outcome misurate sono: mortalità e livello di disabilità a 30 giorni dallo SE, sviluppo di refrattarietà al trattamento e sviluppo di epilessia. Nei pazienti con NCSE, è stata effettuata un’analisi delle caratteristiche dei patterns perfusionali ed EEG.
Ventuno pazienti con NCSE sono stati studiati con CTP ed EEG. In 18 pazienti (86%) è stato evidenziato un pattern di iper-perfusione ed è stata osservata una concordanza spaziale perfetta (100%) tra la sede multilobare dell’iper-perfusione e la sede dell’attività critica focale all’EEG. Tutti i pazienti con patterns epilettici continui all’EEG (12 pazienti) presentavano un pattern di iper-perfusione mentre soltanto 3 su 6 (50%) con patterns EEG discontinui (WWP) avevano iper-perfusione (χ2, p = 0.03).
Per 87 pazienti è stato possibile ottenere i livelli sierici di Nfl e S100B. Nei pazienti con SE, i livelli di entrambi i biomarcatori sono risultati significativamente maggiori rispetto a quelli rilevati nei gruppi di controllo (p 70.25 pg/ml sono risultati un predittore indipendente di mortalità a 30 giorni dopo correzione per età e refrattarietà (OR 6 95% CI 1-36.12 p = 0.05); NfL > 33.4 pg/ml sono risultati predittore indipendente (dopo correzione per età) di sviluppo di disabilità a 30 giorni (OR 3.9 95% CI 1.41-10.64 p = 0.009); NfL > 19.75 pg/ml si sono mostrati un predittore di sviluppo di refrattarietà al trattamento (OR 8.2 95% CI 2.08-32.58 p = 0.003). I livelli sierici di S100B invece sono risultati essere significativamente maggiori nei pazienti deceduti o peggiorati clinicamente ma non sono risultati essere predittori per questi ouctomes. SE responsivi e refrattari non hanno presentato differenze significative nei livelli di S100B. Comparando coloro che hanno sviluppato un’epilessia a coloro per i quali lo SE ha rappresentato un evento isolato, non si sono osservate differenze significative nei livelli di NfL mentre i livelli di S100B sono risultati significativamente ridotti in coloro che hanno sviluppato epilessia successivamente. Tuttavia nessuno dei due biomarcatori rappresenta un predittore di sviluppo di epilessia dopo uno SE.
In conclusione, i patterns CT di iper-perfusione rappresentano un biomarcatore neuroradiologico per supportare la diagnosi di NCSE utile soprattutto nei casi più dubbi. Inoltre, i livelli sierici di NfL sono utili per la prognosticazione in termini di mortalità e morbidità a breve termine e sviluppo di refrattarietà al trattamento.Status Epilepticus (SE) is a common neurological emergency characterized by high short-term morbidity and mortality. Identifying diagnostic and prognostic biomarkers could help in the evaluation and management of SE patients. Beside clinico-electroencefalographic evaluation, a multimodal approach based, on the measurement of neuro-glial injury biomarkers and on the identification of acute neuroimaging alterations related to SE could help both rapidly identifying those patients who will eventually develop short- and long-term consequences of SE and assisting the diagnosis in more doubtful cases. This study aims to: 1. determine the cerebral CT perfusion (CTP) patterns correlated to SE and define their role in supporting the diagnosis of NCSE; 2. define the profile changes of serum and CSF biomarkers of neuro-glial degeneration and their potential prognostic role; 3. define the usefulness of such a multimodal evaluation to improve SE treatment in clinical practice. This is a prospective monocentric collection of adult patients with SE. Enrolled patients underwent to the acquisition of serum samplings during SE within 72 hours from its diagnosis. In these samplings neuro-glial injury biomarkers (neurofilament light chain, NfL, and S100B) were measured. The same fluids’ biomarkers were measured in control groups: age and sex-matched healthy controls (HC) and epileptic patients (EP). Outcome measures were: 30 days mortality and disability, treatment refractoriness and epilepsy development. In NCSE, an analysis of the characteristics of CTP and EEG patterns and their relationship was then made. Twenty-one focal NCSE patients were studied with CTP and EEG in the acute phase. Eighteen patients (86%) had focal hyper-perfusion patterns and 3 (14%) a normo-perfusion patterns. In patients with hyper-perfusion patterns there was a perfect (100%) concordance in spatial localization of focal multilobar cortical hyper-perfusion and focal ictal activity. Among the hyper-perfused patients, all the 12 patients with continuous pattern (CP) showed cortical hyper-perfusion while only 3 out of 6 (50%) with waxing and waning pattern (WWP) had cortical hyper-perfusion (χ2, p = 0.03).
In 87 SE patients serum levels of NfL and S100B were measured. In SE group, serum levels of NfL and S100B were significantly higher compared to those of EP and HC (p < 0.001). NfL above 70.25 pg/ml were found to be an independent predictor of 30 days mortality after correction for age and treatment refractoriness (OR 6 95% CI 1-36.12 p = 0.05); NfL above 33.4 pg/ml showed to be an independent predictor of 30 days disability after correction for age (OR 3.9 95% CI 1.41-10.64 p = 0.009); NfL above 19.75 pg/ml appeared as an independent predictor of refractoriness development (OR 8.2 95% CI 2.08-32.58 p = 0.003). Serum S100B levels appeared significantly higher in patients who died and in those who worsened within 30 days even though they did not appeared to be predictors for these outcome. Moreover, no significant differences were found in serum levels of S100B between responsive and refractory SE. Comparing those who developed epilepsy compared to those for which the SE remained an isolated event, no differences in serum NfL levels were found while serum levels of S100B were significantly lower in patients who developed epilepsy. Nevertheless, neither NfL nor S100B were found to be predictors of epilepsy development after SE.
In conclusion, hyper-perfusion CTP patterns represent a biomarker to assist and support the diagnosis of NCSE in the emergency department setting, especially in doubtful cases. Serum NfL levels seem to be helpful for the prognostication in terms of short-term mortality, functional outcome and refractoriness development
Ictal asystole as the first presentation of epilepsy: A case report and systematic literature review
No full textWe report the case of a 69-year-old woman who presented with recurring episodes of mental confusion/dizziness followed by loss of consciousness, intense pallor, and sweating. Cardiologic investigations were unremarkable. The electroencephalogram recorded during one typical episode allowed the demonstration of a right frontotemporal seizure with progressive bradycardia leading to a 9-second asystole. Following levetiracetam treatment up to 2500 mg/day, seizures with ictal asystole (IA) recurred. An MRI compatible pacemaker was then implanted. At 26-month follow-up, the patient has not had further episodes of loss of consciousness. A systematic review (1950-Apr 2014) searching for cases in which IA was an early manifestation of epilepsy led to the observation of 31 cases. The time lag between the first seizures and the correct diagnosis of IA was long (average: 27 months; median: 12 months). Clinical history alone was not sufficient to prompt a correct diagnosis of IA, and only 11 out of 31 cases presented with symptoms suggestive of a seizure disorder. The majority of patients had a frontotemporal epilepsy with a slight prevalence of left-side involvement (19 out of 31). Ictal bradycardia-asystole is an important condition that should be recognized by epileptologists, neurologists, as well as emergency department physicians. It is important to underscore that IA not only can occur in patients with drug-resistant epilepsy but also may be the first manifestation of the patient's epilepsy
The role of AMPA receptors and their antagonists in status epilepticus
No full textStatus epilepticus (SE) is typically defined as a prolonged self-sustaining seizure or repeated seizures showing an incomplete recovery between them. SE represents a medical emergency often associated with significant disability, morbidity, and mortality. Despite the clinical impact, the mechanisms underlying the transition from self-limited seizures to protracted, medically refractory seizures are not completely understood. About 40% of patients in established SE are refractory to antiepileptic drugs (first-line treatment); therefore, there is a need for more efficacious drugs. In this review, we focused on the current knowledge about the involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors during SE, the preclinical efficacy of its antagonists, and the currently published clinical studies involving drugs with this mechanism of action. We carried out an extensive literature search to recognize experimental and clinical articles both on AMPA receptors and AMPA antagonists and SE. Recently, the role of AMPA receptors during and after SE has become clearer, and it is now widely accepted that early changes occur in the initial stages and probably contribute both to the maintenance of SE and to its refractoriness to treatment. The therapeutic potential of AMPA receptor inhibition has been sustained by studies in which AMPA receptor antagonists have been shown to terminate seizures in several SE animal models. To date, promising, but limited, data in humans support the use of AMPA receptor antagonists in patients with SE. AMPA receptor antagonists could become a new therapeutic option in patients with established SE when the first trials with second-line agents have failed or probably even better after failure of benzodiazepines as a second-line option
Progressive bilateral medial medullary infarction
No full textThis is the report of a rare case of blateral medial medullary infarctio
The risk of unprovoked seizure occurrence after status epilepticus in adults
Full text linkObjective: Status epilepticus (SE) may lead to long-term consequences. This study evaluated the risk and predictors of seizure occurrence after SE, with a focus on SE due to acute symptomatic etiologies. Methods: Prospectively collected data about adults surviving a first non-hypoxic SE were reviewed. The outcome was the occurrence of unprovoked seizures during the follow-up. Kaplan-Meier survival curve analysis and log-rank test were used to analyze the time to seizure occurrence and determine the statistical significance between etiological groups. Three subcategories within acute etiology were considered according to the presence of the following: (1) structural lesion (acute-primary); (2) brain involvement during systemic disorders (acute-secondary); and (3) drug or alcohol intoxication/withdrawal (acute-toxic). Cox proportional hazards model was adopted to estimate hazard ratios (HRs) with the 95% confidence intervals (CIs). Results: Two hundreds fifty-seven individuals were included. Fifty-four subjects (21.0%) developed seizures after a median of 9.9 (interquartile range 4.3-21.7) months after SE. The estimated 1-, 2-, and 5-year rates of seizure occurrence according to acute SE etiologies were 19.4%, 23.4%, and 30.1%, respectively, for acute-primary central nervous system (CNS) pathology; 2.2%, 2.2%, and 8.7%, respectively, for acute-secondary CNS pathology; and 0%, 9.1%, and 9.1%, respectively, for acute-toxic causes. Five-year rates of seizure occurrence for non-acute SE causes were 33.9% for remote, 65.7% for progressive, and 25.9% for unknown etiologies. In multivariate Cox regression model, progressive etiology (adjusted HR [adjHR] 2.27, 95% CI 1.12-4.58), SE with prominent motor phenomena evolving in non-convulsive SE (adjHR 3.17, 95% CI 1.38-7.25), and non-convulsive SE (adjHR 2.38, 95% CI 1.16-4.90) were independently associated with higher hazards of unprovoked seizures. Older people (adjHR .98, 95% CI .96-.99) and people with SE due to acute-secondary CNS pathology (adjHR .18, 95% CI .04-.82) were at decreased risk of seizure occurrence. Significance: SE carries a risk of subsequent seizures. Both the underlying cause and epileptogenic effects of SE are likely to contribute
DRUG-RESISTANT EPILEPSY AFTER A FIRST UNPROVOKED SEIZURE IN ADOLESCENCE AND ADULTHOOD: A PROSPECTIVE COHORT STUDY
No full textLow levels of progesterone and derivatives in cerebrospinal fluid of patients affected by status epilepticus
No full textNeurosteroids such as allopregnanolone may play a role in epilepsy as positive modulators of inhibitory currents mediated by γ-aminobutyric acid type A (GABAA ) receptor. Indeed, these molecules have been consistently shown to be anticonvulsants in animal models, but their role is still unclear in patients. For this reason, we investigated neurosteroids in the cerebrospinal fluid (CSF) of patients with status epilepticus (SE) by liquid chromatography tandem-mass spectrometry. Patients were retrospectively identified within subjects who received a lumbar puncture in the 2007-2017 period. Seventy-three patients (median age 65, ranging from 13 to 94 years; 67% women) with SE were evaluated. Controls (n = 52, median age 53, ranging from 16 to 93 years; 65% women) were patients presenting with symptoms for which a lumbar puncture was required by clinical guidelines, and who were negative at the end of the diagnostic work-up. Progesterone was 64% lower in patients with SE (p < 0.001). With respect to progesterone, upstream pregnenolone sulfate and pregnenolone did not change. Instead, downstream 5α-dihydroprogesterone, pregnanolone and allopregnanolone were respectively 49% (p < 0.001), 21% (p < 0.01) and 37% (p < 0.001) lower than in controls. Duration or type of SE, age and sex did not consistently affect CSF neurosteroid levels in the SE cohort. Instead, pregnenolone sulfate (Spearman's ρ = 0.4335, p < 0.01), allopregnanolone (ρ = 0.4121, p < 0.05), and pregnanolone (ρ = 0.592, p < 0.001) levels significantly increased by ageing in controls. We conclude that neurosteroidogenesis is defective in patients with SE. This article is protected by copyright. All rights reserved
Decreased allopregnanolone levels in cerebrospinal fluid obtained during status epilepticus
Full text linkNeuroactive steroids are increasingly considered as relevant modulators of neuronal activity. Especially allopregnanolone (AP) and pregnenolone sulfate (PS) have been shown to possess, respectively, anticonvulsant or proconvulsant properties. In view of the potential role of these steroids, we aimed at evaluating AP and PS levels in cerebrospinal fluid (CSF) and blood samples obtained from patients with status epilepticus (SE). To this purpose, we enrolled 41 patients affected by SE and 41 subjects investigated for nonepileptic neurologic disorders. Liquid chromatographic procedures coupled with electrospray tandem mass spectrometry and routine laboratory investigations were performed. Significantly lower AP levels were found in the CSF of patients affected by SE (-30%; p < 0.05, Mann-Whitney test). Notably, AP was not detectable in 28 of 41 patients affected by SE (p < 0.01 vs. controls, Fisher's exact test). In serum, AP levels did not differ in the two considered groups. Conversely, PS was present at similar levels in the investigated groups. Finally, differences in AP levels could not be explained by a variation in CSF albumin content. These findings indicate that AP is defective in the CSF of patients affected by SE. This phenomenon was not dependent on carriers for steroids, such as albumin
How much refractory is 'refractory status epilepticus'? A retrospective study of treatment strategies and clinical outcomes
No full textBackground and purposeThis study aimed to evaluate whether differences in clinical outcomes exist according to treatments received and seizure activity resolution in patients with refractory status epilepticus (RSE).MethodsConsecutive episodes of non-hypoxic status epilepticus (SE) in patients & GE; 14 years old were included. Episodes of RSE were stratified in: (i) SE persistent despite treatment with first-line therapy with benzodiazepines and one second-line treatment with antiseizure medications (ASMs), but responsive to successive treatments with ASMs (RSE-rASMs); (ii) SE persistent despite treatment with first-line therapy with benzodiazepines and successive treatment with one or more second-line ASMs, but responsive to anesthetic drugs [RSE-rGA (general anesthesia)]. Study endpoints were mortality during hospitalization and worsening of modified Rankin Scale (mRS) at discharge.ResultsStatus epilepticus was responsive in 298 (54.1%), RSE-rASMs in 152 (27.6%), RSE-rGA in 46 (8.3%), and super-refractory (SRSE) in 55 (10.0%) out of 551 included cases. Death during hospitalization occurred in 98 (17.8%) and worsening of mRS at discharge in 287 (52.1%) cases. Multivariable analyses revealed increased odds of in-hospital mortality with RSE-rGA (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.27-7.35) and SRSE (OR 3.83, 95%. CI 1.73-8.47), and increased odds of worsening of mRS with RSE-rASMs (OR 2.06, 95% CI 1.28-3.31), RSE-rGA (OR 4.44, 95% CI 1.97-10.00), and SRSE (OR 13.81, 95% CI 5.34-35.67).ConclusionsIn RSE, varying degrees of refractoriness may be defined and suit better the continuum spectrum of disease severity and the heterogeneity of SE burden and prognosis
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