Exploratory study of blood biomarkers in patients with post-stroke epilepsy.

INTRODUCTION: In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE. PATIENTS AND METHODS: From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE. RESULTS: Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1-25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients (p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601-0.865). DISCUSSION AND CONCLUSION: Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.

Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

BACKGROUND AND OBJECTIVES: The occurrence of seizures after aneurysmal subarachnoid hemorrhage (aSAH) is associated with a poorer functional and cognitive prognosis and less favorable quality of life. It would be of value to promptly identify patients at risk of epilepsy to optimize follow-up protocols and design preventive strategies. Our aim was to develop a predictive score to help stratify epilepsy risk in patients with aSAH. METHODS: This is a retrospective, longitudinal study of all adults with aSAH admitted to our center (2012-2021). We collected demographic data, clinical and radiologic variables, data on early-onset seizures (EOSs), and data on development of epilepsy. Exclusion criteria were previous structural brain lesion, epilepsy, and ≤7 days' follow-up. Multiple Cox regression was used to evaluate factors independently associated with unprovoked remote seizures (i.e., epilepsy). The best fitting regression model was used to develop a predictive score. Performance was evaluated in an external validation cohort of 308 patients using receiver-operating characteristic curve analysis. RESULTS: From an initial database of 743 patients, 419 met the inclusion criteria and were included in the analysis. The mean age was 60 ± 14 years, 269 patients (64%) were women, and 50 (11.9%) developed epilepsy within a median follow-up of 4.2 years. Premorbid modified Rankin Score (mRS) (hazard ratio [HR] 4.74 [1.8-12.4], p = 0.001), VASOGRADE score (HR 2.45 [1.4-4.2], p = 0.001), surgical treatment (HR 2.77 [1.6-4.9], p = 0.001), and presence of EOSs (HR 1.84 [1.0-3.4], p = 0.05) were independently associated with epilepsy. The proposed scale, designated RISE, scores 1 point for premorbid mRS ≥ 2 (R), VASOGRADE-Yellow (I, Ischemia), surgical intervention (S), and history of EOSs (E) and 2 points for VASOGRADE-Red. RISE stratifies patients into 3 groups: low (0-1), moderate (2-3), and high (4-5) risk (2.9%, 20.8%, and 75.7% developed epilepsy, respectively). On validation in a cohort from a different tertiary care center (N = 308), the new scale yielded a similar risk distribution and good predictive power for epilepsy within 5 years after aSAH (area under the curve [AUC] 0.82; 95% CI 0.74-0.90). DISCUSSION: The RISE scale is a robust predictor of post-SAH epilepsy with immediate clinical applicability. In addition to facilitating personalized diagnosis and treatment, RISE may be of value for exploring future antiepileptogenesis strategies.

Antiseizure medication withdrawal in adult patients with idiopathic generalized epilepsy: Performance of two seizure recurrence prediction models.

PURPOSE: Currently, there is a limited availability of tools to predict seizure recurrence after discontinuation of antiseizure medications (ASMs). This study aimed to establish the seizure recurrence rate following ASM cessation in adult patients with idiopathic generalized epilepsy (IGE) and to assess the predictive performance of the Lamberink and the Stevelink prediction models using real-world data. METHODS: Retrospective longitudinal study in IGE patients who underwent ASM withdrawal in a tertiary epilepsy clinic since June 2011, with the latest follow up in January 2024. The minimum follow-up period was 12 months. Clinical and demographic variables were collected, and the seizure recurrence prediction models proposed by Lamberink and Stevelink were applied and evaluated. RESULTS: Forty-seven patients (mean age 33.15 ± 8 [20-55] years; 72.35 % women) were included. During the follow-up period, seizures recurred in 25 patients (53.2 %). Median time to recurrence was 8 months [IQR 3-13.5 months], and 17 patients (68 %) relapsed within the first year. None of the relapsing patients developed drug-resistant epilepsy. The only significant risk factor associated with recurrence was a seizure-free period of less than 2 years before discontinuing medication (91.7 % vs 40 %, p =.005). The Stevelink prediction model at both 2 (p =.015) and 5 years (p =.020) achieved statistical significance, with an AUC of 0.72 (95 % CI 0.56-0.88), while the Lamberink model showed inadequate prognostic capability. CONCLUSION: In our real-world cohort, a seizure-free period of at least 2 years was the only factor significantly associated with epilepsy remission after ASM withdrawal. Larger studies are needed to accurately predict seizure recurrence in IGE patients.

Ketamine in the treatment of refractory and super-refractory status epilepticus: Experience from two centres.

PURPOSE: There is insufficient evidence on the management of refractory status epilepticus (RSE) and super-RSE (SRSE). Ketamine is a N-methyl-d-aspartate receptor antagonist in the treatment of these entities. Our objectives were to study the effectiveness and safety of ketamine in the treatment of adult patients with RSE and SRSE, to determine the factors that can influence the response to ketamine, and to explore its use in patients without mechanical ventilation. METHODS: Adult patients who had received intravenous ketamine for the treatment of RSE or SRSE at Hospital Universitario Clínico San Carlos (Madrid, Spain) or Hospital Universitari Vall d'Hebron (Barcelona, Spain) from 2017 to 2023 were retrospectively analysed. RESULTS: This study included 58 adult patients, mean (standard deviation) age 60.2 (15.7) years, of whom 41 (70.7 %) were male; 33 (56.9 %) patients responded to ketamine without recurrence, with a low rate of adverse effects (8.6 %). The presence of SRSE at the time of ketamine initiation (OR 0.287, p = 0.028) and the time elapsed between status epilepticus onset and ketamine administration (OR 0.991, p = 0.034) were associated with worse response to ketamine. Patients treated without mechanical ventilation had similar rates of response without recurrence (62.5% vs 56.9 %) and lower mortality (37.5% vs 53.5 %) compared to the overall group. CONCLUSION: Ketamine is an effective drug with few adverse effects. Prompt administration should be considered in patients with RSE requiring anaesthesia, in patients with SRSE, and in patients with RSE who do not respond to standard antiseizure drugs and in whom mechanical ventilation is not advised.

Risk assessment of long-term epilepsy after de novo status epilepticus with clinical and electroencephalographic biomarkers: The AFTER score.

BACKGROUND: The risk of developing epilepsy after de novo status epilepticus (SE) is nonnegligible. The individualized management of patients with high risk of subsequent epilepsy could improve long-term quality of life and cognitive impairment. We aimed to ascertain potential biomarkers of subsequent epilepsy and to construct a scoring system possessing predictive value for the diagnosis of post-SE epilepsy during follow-up. METHODS: The study data were obtained from a prospective registry of all SE episodes occurring in patients over 16 years attended in our tertiary center from February 2011 to April 2022. Clinical data, electroencephalography findings, treatment, and long-term clinical data were prospectively recorded. We selected SE patients at risk of developing epilepsy (acute symptomatic and cryptogenic etiologies with no previous history of epilepsy) and analyzed the risk of developing subsequent epilepsy. RESULTS: We included 230 patients. Median age was 65 years ± 16.9 SD and 112/230 (48.7 %) were women. One-hundred ninety-eight patients (86.1 %) had an acute symptomatic SE, whereas 32 patients (13.9 %) presented with a cryptogenic SE. A total of 55 patients (23.9 %) developed an unprovoked remote seizure and were diagnosed with epilepsy. After adjusting for identifiable confounders in a multivariable Cox regression analysis cryptogenic etiology (HR 2.24 [1.13-4.46], p = 0.022), first-line treatment initiation ≥1 h (HR 2.12 [1.03-4.36], p = 0.041], RDA/LPD/GPD EEG patterns (HR 1.88 [1.07-3.32], p = 0.028), and super-refractoriness (HR 2.90 [1.40-5.99], p = 0.004) emerged as independent predictors of post-SE epilepsy. Based on these findings, we constructed the AFTER score (1 point for each item) with a robust capability to predict post-SE epilepsy at 5 years (AUC 74.3 %, 95 %CI 64.3-84.3 %, p < 0.001). CONCLUSIONS: The AFTER score is a robust predictor of the development of epilepsy after new onset SE using clinical and electroencephalographic biomarkers (such as etiology, time to first-line treatment initiation, EEG pattern and super-refractoriness). Prospective studies are warranted to validate the score in other populations.

Prediction of long-term unprovoked seizures after status epilepticus.

OBJECTIVE: Possible long-term consequences of status epilepticus (SE) include cognitive and behavioral impairment and the development of chronic epilepsy. However, these aspects have not been systematically studied in clinical practice. We aimed to evaluate long-term seizure recurrence after SE and the potential risk factors for their development. METHODS: Data were obtained from a prospective registry of all SE episodes occurring in adult patients who attended our center from February 2011 to April 2022. Clinical data, electroencephalographic findings, treatment, and long-term data were prospectively recorded. We performed a cross-sectional study of consecutive SE patients without previous epilepsy diagnosis, and analyzed the development of unprovoked remote seizures. RESULTS: A total of 849 patients were registered in the database. After excluding in-hospital mortality (198/849, 23.3%) and patients with prior epilepsy history (291/849, 44.7%), 360 patients (42.4%) with a first SE episode were included. The median age was 68 years (interquartile range [IQR] = 56-79), and 176 patients (48.9%) were women. The median time to first-line treatment initiation was 2 h (IQR = .7-7.4), and it was correlated with SE duration (R = .375, p < .001). One hundred nine patients (30.3%) presented unprovoked seizures during a median follow-up of 1.8 years (IQR = .5-4.3). After adjusting for identifiable confounders in a multivariable Cox regression analysis, progressive symptomatic etiology (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.33, p = .011), time to first-line treatment initiation > 1.5 h (HR = 1.89, 95% CI = 1.25-2.87, p = .003), and superrefractory SE (HR = 2.34, 95% CI = 1.26-4.33, p = .007) were independently associated with a greater risk of unprovoked seizure recurrence. In contrast, older patients (HR = .99, 95% CI = .97-.99, p = .021) and an acute symptomatic etiology (HR = .44, 95% CI .28-.68, p < .001) were at lower risk of unprovoked seizure recurrence. SIGNIFICANCE: The etiology of SE, the delay in initiating SE treatment, and the presence of superrefractoriness have been identified as potentials factors associated with unprovoked remote seizures following a new onset SE. Therefore, prompt and appropriate management should be applied to avoid seizure recurrence.

The mediating role of epileptic seizures, irritability, and depression on quality of life in people with epilepsy.

PURPOSE: Psychiatric comorbidity is common in epilepsy and has a considerable impact on patient quality of life (QoL). This study aimed to analyze the relationship between seizure frequency, irritability, and depression and describe how they mediate each other's effect on QoL in epilepsy. METHODS: This is a cross-sectional study of consecutive adults seen at an outpatient epilepsy clinic of a tertiary hospital in Barcelona, Spain. All the patients were evaluated for psychiatric comorbidity and administered the State-Trait Anger Expression Inventory-2 (STAXI-2), the Hospital Anxiety and Depression Scale (HADS), and the Quality Of Life in Epilepsy Inventory-10 (QOLIE-10). Mediation analysis with multiple linear regression followed by the Sobel test was performed. RESULTS: We studied 157 patients. Seizure frequency (R = -0.193, P = .053), irritability (R = 0.216, P = .039), and depression (R = -0.598, P < .001) had all a negative effect on QoL. In the adjusted linear regression model, depression was the only independent predictor of impaired QoL (B = -2.453 [95% confidence interval (CI): -3.161, -1.744], P < .001). The Sobel test showed that depression exerted a significant mediating effect on seizure frequency (Z = -1.984; P = .047) and irritability (Z = -3.669; P < .001) in their influence on QoL. CONCLUSION: Depression is an independent predictor of worse QoL and significantly mediated the effects of irritability and poor seizure control on QoL impairment in patients with epilepsy.

Síndrome de seno cavernoso secundario a una tromboflebitis por Streptococcus intermedius complicada con vasculitis de la arteria carótida interna y abscesos cerebrales / Cavernous sinus syndrome secondary to thrombophlebitis due to Streptococcus intermedius complicated with vasculitis of the internal carotid artery and brain abscesses

Introducción: La tromboflebitis del seno cavernoso es una enfermedad infecciosa grave con alta mortalidad y morbilidad. Su diagnóstico suele ser tardío y requiere múltiples visitas a urgencias en la mayoría de casos, y el pronóstico es altamente dependiente de su rápido tratamiento. A pesar de su gravedad, la evidencia con respecto al tratamiento con corticoides y anticoagulación es escasa y controvertida. Entre sus complicaciones se encuentra la arteritis, la cual puede confundirse con una vasculitis de mediano-gran vaso, como en este caso. Caso clínico: Mujer de 26 años, que acude por una cefalea y un edema palpebral izquierdo. En las pruebas de imagen se evidencia trombosis del seno cavernoso izquierdo y una estrechez importante de la arteria carótida interna. Se interpreta el cuadro como secundario a un proceso vascular inflamatorio y se inician corticoides, con buena respuesta. Sin embargo, al poco tiempo se presenta fiebre y edema palpebral contralateral. En los hemocultivos se obtiene un crecimiento de Streptococcus intermedius y se diagnostica una tromboflebitis del seno cavernoso. A pesar del inicio de antibióticos y anticoagulación, sufre una hemiplejía derecha secundaria a la formación de abscesos frontotemporales. Se procede al drenaje quirúrgico y la paciente cursa con buena evolución. Ante la ausencia de otros focos infecciosos, y debido a la procedencia oral del germen, se realiza una exodoncia múltiple profiláctica. Conclusión: Se recomienda considerar la tromboflebitis como una opción diagnóstica tanto en las cefaleas con síntomas oculares como en la arteritis de mediano-gran vaso para su tratamiento oportuno

Introduction: Thrombophlebitis of the cavernous sinus is a severe infectious disease with high mortality and morbidity. It is usually diagnosed at a late stage and requires a number of visits to the emergency department in most cases, and the prognosis is highly dependent on prompt treatment. Despite its severity, evidence regarding treatment with corticosteroids and anticoagulation therapy is scarce and controversial. One of its complications is arteritis, which can be mistaken for medium to large vessel vasculitis, as in this case. Case Report: A 26-year-old female, who visited due to headache and left palpebral oedema. Imaging tests revealed thrombosis in the left cavernous sinus and significant narrowing of the internal carotid artery. The clinical picture was interpreted as secondary to an inflammatory vascular process and treatment with corticosteroids was initiated, with a good response. However, soon afterwards, fever and contralateral palpebral oedema developed. In the blood cultures a growth of Streptococcus intermedius was obtained and thrombophlebitis of the cavernous sinus was diagnosed. Despite initiating antibiotic and anticoagulation therapy, the patient suffered a right hemiplegia secondary to the formation of frontotemporal abscesses. Surgical drainage was performed and the patient progressed well. In the absence of other infectious foci, and due to the oral origin of the germ, a prophylactic multiple exodontia was performed. Conclusion: Thrombophlebitis should be considered as a diagnostic option both in headaches with ocular symptoms and in medium to large vessel arteritis so that they can be treated in a timely manner

Leucoencefalopatía multifocal progresiva y disfunción inmune no especificada / Progressive multifocal leukoencephalopathy and non-specific immune dysfunction

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