Epileptiform electroencephalogram discharges increase seizure recurrence risk in patients with acute symptomatic seizure due to a structural brain lesion.

OBJECTIVE: The risk factors for seizure recurrence after acute symptomatic seizure due to a structural brain lesion are not well established. The aim of this study was to analyze possible associations between demographic, clinical, and electroencephalographic variables and epilepsy development in patients with acute symptomatic seizure due to an acute structural brain lesion. METHODS: We designed an observational prospective study of patients with acute symptomatic seizure due to an acute structural brain lesion (hemorrhagic stroke, ischemic stroke, traumatic brain injury, or meningoencephalitis) who underwent EEG during their initial admission between January 2015 and January 2020. We analyzed prospectively recorded demographic, clinical, electroencephalographic (EEG), and treatment-related variables. All variables were compared between patients with and without seizure recurrence during 2 years of follow up. RESULTS: We included 194 patients (41.2 % women; mean [SD] age, 57.3 [15.8] years) with acute symptomatic seizure due to an acute structural brain lesion. They all underwent EEG during admission and were followed for at least 2 years. The identifiable causes were hemorrhagic stroke (44.8 %), ischemic stroke (19.5 %), traumatic brain injury (18.5 %), and meningoencephalitis (17 %). Fifty-six patients (29 %) experienced a second seizure during follow-up. Seizure recurrence was associated with epileptiform discharges on EEG (52% vs 32 %; OR 2.3 [95 % CI, 1.2-4.3], p = 0.008) and onset with status epilepticus (17% vs 0.05 %, OR 4.03 [95 % CI 1.45-11.2], p = 0.009). CONCLUSIONS: Epileptiform discharges on EEG and status epilepticus in patients with acute symptomatic seizure due to an acute structural brain lesion are associated with a higher risk of epilepsy development.

Time of the day and season distribution among stroke code subtypes: differences between ischemic stroke, intracranial hemorrhage, and stroke mimic.

Background: Circadian variations in the timing of the onset of stroke symptoms have been described, showing a morning excess of cardiovascular risk. To date, no differences have been found between stroke subtype and time distribution throughout the day. The present study aims to compare the seasonal and circadian rhythm of symptoms onset in ischemic, hemorrhagic, and stroke mimic patients. Methods: This study was conducted prospectively at a hospital and involved a cohort of stroke alert patients from 2018 to 2021. Stroke subtypes were classified as ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack (TIA), and stroke mimic. Clinical variables were recorded, and each patient was assigned to a 4-h interval of the day according to the time of onset of symptoms; unwitnessed stroke patients were analyzed separately. Seasonal changes in stroke distribution were analyzed at 3-month intervals. Results: A total of 2,348 patients were included in this analysis (ischemic 67%, ICH 13%, mimic 16%, and TIA 3%). Regardless of stroke subtype, most of the patients were distributed between 08-12 h and 12-16 h. Significant differences were found in the time distribution depending on stroke subtype, with ICH predominating in the 4-8 h period (dawn), most of which were hypertensive, TIA in the 12-16 h period (afternoon), and stroke mimic in the 20 h period (evening). The ischemic stroke was evenly distributed throughout the different periods of the day. There were no differences in the seasonal pattern between different stroke subtypes, with winter being the one that accumulated the most cases. Conclusion: The present study showed different circadian patterns of stroke subtypes, with a predominance of ICH at dawn and stroke mimic in the afternoon. The stroke circadian rhythm resembles previous studies, with a higher incidence in the morning and a second peak in the afternoon.

Two Practical and Efficient Approaches to Fluorinated and Nonfluorinated Chiral beta-Imino Sulfoxides.

Reaction of fluorinated and nonfluorinated N-substituted imidoyl chlorides 1 with lithium derivatives of enantiopure methyl p-tolyl sulfoxide 2a (or racemic methyl phenyl sulfoxide 2b) gave a wide variety of chiral N-substituted beta-imino sulfoxides 4 in good to excellent yields. The title compounds (R)-4 were also prepared by aza-Wittig reaction of gamma-fluoro-beta-keto sulfoxides (R)-5 and N-aryl iminophosphoranes 6. The imino-enamino equilibrium was studied, showing, in all instances, the imino form as the predominant tautomer independent of the nature of the N-substituent. The configuration of the C=N double bond was found to be Z for both N-alkyl and N-aryl derivatives on the basis of (1)H NMR NOE difference experiments performed over several compounds. Ab initio calculations (HF/6-31G) carried out on several representative examples of 1 and 4 are, in general, consistent with the experimental results.

New Strategies for the Synthesis of Fluorinated Vinylogous Amidines and beta-Enamino Ketones.

Reaction of fluorinated imidoyl chlorides 3 with ketimines 1a provides fluorinated 1,3-diimines, which were exclusively isolated as vinylogous amidine tautomers 2beta, with good yields. Fluorinated beta-enamino ketones 4 are obtained by regioselective hydrolysis of 2. Complementary methods for the synthesis of regioisomeric beta-enamino ketones 4 and 5 are also reported. These methods include the reaction of azaenolates of ketimines with fluorinated esters 6 and reactions of ketone enolates with fluorinated imidoyl chlorides 3. The behavior of these systems in hydrolysis reactions was also tested.

New strategy for the stereoselective synthesis of fluorinated beta-amino acids.

Racemic and chiral nonracemic alpha-substituted and alpha-unsubstituted beta-fluoroalkyl beta-amino acid derivatives 6 and 9 have been synthesized in two steps starting from fluorinated imidoyl chlorides 1 and ester enolates. This approach is based on the chemical reduction of previously obtained gamma-fluorinated beta-enamino esters 4 by using ZnI(2)/NaBH(4) in a nonchelated aprotic medium (dry CH(2)Cl(2)) as the reducing agent. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction. The process takes place with high yields and with moderate to good diastereoselectivity. The best results related to diastereoselective reduction of chiral beta-enamino esters 4 were provided by the use of (-)-8-phenylmenthol as a chiral auxiliary.