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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.
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Vigilancia de la Población , Estado Epiléptico/diagnóstico , Estado Epiléptico/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Austria/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodos , Estudios Retrospectivos , Estado Epiléptico/clasificación , Resultado del Tratamiento , Adulto JovenRESUMEN
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.
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Anticonvulsivantes/uso terapéutico , Piridonas/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Austria , Electroencefalografía , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Nitrilos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
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.
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Anticonvulsivantes/administración & dosificación , Pirrolidinonas/administración & dosificación , Estado Epiléptico/tratamiento farmacológico , Resultado del Tratamiento , Administración Intravenosa , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Early recognition and treatment of autoimmune encephalitis (AE) has become an essential issue in clinical practice. However, little is known about patients with deteriorating conditions and the need for intensive care treatment. Here, we aimed to characterize underlying aetiologies, clinical symptoms, reasons for intensive care admission, and mortality of critically ill patients with AE. METHODS: We conducted a retrospective chart review of all patients with "definite" or "probable" diagnoses of AE treated at our neurological intensive care unit between 2002 and 2015. We collected and analyzed clinical, paraclinical, laboratory findings and assessed the mortality at last follow-up based on patient records. RESULTS: Twenty-seven patients [median age 55 years (range 25-87), male = 16] were included. Thirteen (48%) had "definite" AE. The most common reasons for admission were status epilepticus (7/27, 26%) and delirium (4/27, 15%). One-year survival was 82%, all five deceased were male, and 3 (60%) of them had "probable" disease. The non-survivors (median follow-up 1 year) were more likely to have underlying cancer and higher need for respiratory support compared to the survivors (p < 0.041, and p = 0.004, respectively). CONCLUSIONS: Clinical presentations and outcomes in critically ill patients with AE are diverse, and the most common leading cause for intensive care unit admission was status epilepticus. The association of comorbid malignancy and the need for mechanical ventilation with mortality deserves further attention.
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Enfermedades Autoinmunes del Sistema Nervioso , Enfermedad Crítica , Delirio , Encefalitis , Unidades de Cuidados Intensivos/estadística & datos numéricos , Estado Epiléptico , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/etiología , Enfermedades Autoinmunes del Sistema Nervioso/mortalidad , Enfermedades Autoinmunes del Sistema Nervioso/terapia , Delirio/diagnóstico , Delirio/etiología , Delirio/mortalidad , Delirio/terapia , Encefalitis/diagnóstico , Encefalitis/etiología , Encefalitis/mortalidad , Encefalitis/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estado Epiléptico/diagnóstico , Estado Epiléptico/etiología , Estado Epiléptico/mortalidad , Estado Epiléptico/terapiaRESUMEN
The aim of our study was to assess whether cerebral artery clots undergo time-dependent morphological and compositional changes in acute ischemic stroke. We performed a retrospective chart review of patients admitted within 5 h from symptom onset to three European stroke centers and evaluated non-contrast-enhanced CT (NECT) for hyperdense artery signs (HAS) in 2565 scans. The occlusion site, density of HAS expressed in Hounsfield units (HU), area of HAS, and relative density (rHU) (HU clot/HU non-affected artery) were studied and related to time from symptom onset, clinical severity, stroke etiology, and laboratory parameters. A HAS was present in the middle cerebral artery (MCA) in 185 (7.2%) and further explored. The mean time from symptom onset to CT was 100 min (range 17-300). We found a time-dependent loss of density in the occluded M1 segment within the first 5 h (N = 118, 95% CI [-15, -2], p = 0.01). Further, the thrombus area in the M2 segment decreased with time (cubic trend N = 67, 95% CI [-63, -8], p = 0.02). Overall, and especially in the M2 segment, a lower clot area was associated with higher fibrinogen (-21.7%, 95% CI [-34.8, -5.8], p = 0.009). In conclusion, our results disclosed time-dependent changes of intracranial thrombi with regard to occlusion site, density and area.
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Isquemia Encefálica/patología , Trombosis Intracraneal/patología , Arteria Cerebral Media/patología , Accidente Cerebrovascular/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Isquemia Encefálica/diagnóstico por imagen , Femenino , Fibrinógeno/metabolismo , Humanos , Trombosis Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/diagnóstico por imagen , Neuroimagen , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Therapeutic plasma exchange (TPE) is a well-established method of treatment for steroid-refractory relapses in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Little is known about indications and clinical responses to TPE in autoimmune encephalitis and other immune-mediated disorders of the central nervous system (CNS). We performed a retrospective chart review of patients with immune-mediated disorders of the CNS undergoing TPE at our tertiary care center between 2003 and 2015. The response to TPE within a 3- to 6-month follow-up was scored with an established rating system. We identified 40 patients including 21 patients with multiple sclerosis (MS, 52.5%), 12 with autoimmune encephalitis (AE, 30%), and 7 with other immune-mediated CNS disorders (17.5%). Among patients with AE, eight patients had definite AE (Immunolobulin G for N-methyl-D-aspartate receptor n = 4, Leucine-rich, glioma inactivated 1 n = 2, Ma 2 n = 1, and Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid n = 1). Intravenous immunoglobulins had been given prior to TPE in all but one patient with AE, and indications were dominated by acute psychosis and epileptic seizures. While TPE has a distinct place in the treatment sequence of different immune-mediated CNS disorders, we found consistent efficacy and safety. Further research should be directed toward alternative management strategies in non-responders.
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Proximal collaterals may determine the composition of occluding thrombi in acute ischemic stroke (AIS) in addition to source, hematocrit, time, and medication. Here, we performed a retrospective study of 39 consecutive patients with radiological evidence of I-, L-, and T-type terminal internal carotid artery occlusion. Middle cerebral artery (MCA) thrombus density was assessed on noncontrast enhanced CT and proximal collaterals on CT angiography. In patients with presence of proximal collaterals to the MCA we detected more hyperdense clots (P = 0.003) and a higher frequency of leptomeningeal collaterals (P = 0.008). We expand the spectrum of factors that potentially determine clot perviousness and evolution of ischemic stroke.
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BACKGROUND: Prevention and early recognition of critical illness in patients with autoimmune encephalitis (AE) is essential to achieve better outcome. AIM OF THE STUDY: To evaluate risk factors for intensive care unit (ICU) admission and its prognostic impact in patients with AE. PATIENTS AND METHODS: A reclassification of patients hospitalized between 2011 and 2016 revealed 17 "definite" and 15 "probable" AE cases. Thirteen patients (41%) developed critical illness and required ICU admission. The underlying conditions were intractable seizures or status epilepticus (54%), altered mental state (39%), and respiratory failure (8%). RESULTS: ICU admission was associated with longer time from first symptoms to hospitalization (p = 0.046). Regression analysis revealed that anemia on hospital admission and definite diagnosis of AE was associated with a higher risk of acquiring critical illness. At last follow-up after a median of 31 months (range 2.5-52.4), seven patients had died (23%) and 63% had a good outcome [modified Rankin Scale (mRS) 0-3]. Anemia was associated with poor prognosis (p = 0.021), whereas development of critical illness did not impact mortality and functional outcome. CONCLUSION: We confirmed the need for ICU care in a subgroup of patients and the prevailing objective is improved seizure control, and definite diagnosis of AE and anemia were identified as risk factors for development of critical illness. However, prognosis was not affected by ICU admission.
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OBJECTIVE: Nontraumatic spinal cord injuries (NTSCIs) form a heterogeneous group of diseases, which may evolve into a life-threatening condition. We sought to characterize spectrum, causes of admission and predictors of death in patients with NTSCI treated at the neurological intensive care unit (NICU). METHODS: We performed a retrospective observational analysis of NTSCI cases treated at a tertiary care center between 2001 and 2013. Among the 3937 NICU admissions were 93 patients with NTSCI (2.4%). Using multivariate logistic regression analysis, we examined predictors of mortality including demographics, etiology, reasons for admission and GCS/SAPS (Glasgow Coma Scale/Simplified Acute Physiology Score) scores. RESULTS: Infectious and inflammatory/autoimmune causes made up 50% of the NTSCI cases. The most common reasons for NICU admission were rapidly progressing paresis (49.5%) and abundance of respiratory insufficiency (26.9%). The mortality rate was 22.6% and 2.5-fold higher than in the cohort of all other patients treated at the NICU. Respiratory insufficiency as the reason for NICU admission [odds ratio (OR) 4.97, 95% confidence interval (CI) 1.38-17.9; p < 0.01], high initial SAPS scores (OR 1.04; 95% CI 1.003-1.08; p = 0.04), and the development of acute kidney injury throughout the stay (OR 7.25, 1.9-27.5; p = 0.004) were independent risk factors for NICU death. CONCLUSIONS: Patients with NTSCI account for a subset of patients admitted to the NICU and are at risk for adverse outcome. A better understanding of predisposing conditions and further knowledge of management of critically ill patients with NTSCI is mandatory.
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BACKGROUND: Over the course of multiple sclerosis (MS) several conditions may arise that require critical care. We aimed to study the reasons for admission and outcome in patients with MS admitted to a neuro-intensive care unit (NICU). METHODS: We retrospectively searched the electronic charts of a 9-bedded NICU in a tertiary hospital for patients with a diagnosis of multiple sclerosis (MS) from 1993-2015, and matched them to NICU controls without MS based on age and gender. Conditional logistic regression was used to compare admission causes, Charlson's Comorbidity Index, indicators of disease severity, and survival between MS and non-MS patients. RESULTS: We identified 61 MS patients and 181 non-MS controls. Respiratory dysfunction was the most frequent reason for NICU admission among MS patients (34.4%), having infectious context as a rule. In a matched analysis, after adjusting for co-morbidities and immunosuppressive medications, patients with MS were more likely to be admitted to the NICU because of respiratory dysfunction (OR = 7.86, 95% CI 3.02-20.42, p<0.001), non-respiratory infections (OR = 3.71, 95% CI 1.29-10.68, p = 0.02), had a higher rate of multiple NICU admissions (OR = 2.53, 95% CI 1.05-6.05, p = 0.04) than non-MS patients. Mortality after NICU admission at a median follow-up time of 1 year was higher in MS than control patients (adjusted OR = 4.21, 95% CI 1.49-11.85, p = 0.04). CONCLUSION: The most common reason for NICU admission in MS patients was respiratory dysfunction due to infection. Compared to non-MS patients, critically ill MS patients had a higher NICU re-admission rate, and a higher mortality.