Background
The use of CD20-depleting monoclonal antibodies has shown to improve the long-term outcome of patients with anti-leucine-rich glioma-inactivated protein 1 antibodies (anti-LGI1-Abs) ...encephalitis after first-line immunotherapy, but currently predictive markers of treatment response and disease activity are lacking.
Case presentation
A 75-year-old man presented cognitive impairment and faciobrachial dystonic seizures (FBDS), with mild abnormalities at electroencephalography (EEG), normal brain magnetic resonance and cerebrospinal fluid (CSF) analysis. Anti-LGI1-Abs were detected in serum and CSF, and corticosteroids and intravenous immunoglobulins were administered. Despite partial cognitive improvement, 18F-fluoridesoxyglucose-positron emission tomography (18F-FDG-PET) showed the persistence of temporo-mesial hypermetabolism, and FBDS were still detected by long-term monitoring video EEG (LTMV EEG). Rituximab was therefore administered with FBDS disappearance, further cognitive improvement, and resolution of 18F-FDG-PET temporo-mesial hypermetabolism.
Conclusions
Our experience supports the use of 18F-FDG-PET and LTMVEEG as useful tools to measure disease activity, evaluate treatment response and guide therapeutic decisions in the long-term management of anti-LGI1-antibody encephalitis.
Objective
Discontinuation of antiepileptic drugs (AEDs) in seizure‐free patients is an important goal because of possible long‐term side effects and the social stigma burden of epilepsy. The purpose ...of this work was to assess seizure recurrence risk after suspension of AEDs, to evaluate predictors for recurrence, and to investigate the recovery of seizure control after relapse. In addition, the accuracy of a previously published prediction model of seizure recurrence risk was estimated.
Methods
Seizure‐free patients with epilepsy who had discontinued AEDs were retrospectively enrolled. The frequency of seizure relapses after AED withdrawal as well as prognosis after recurrence were assessed and the predictive role of baseline clinical‐demographic variables was evaluated. The aforementioned prediction model was also validated and its accuracy assessed at different seizure‐relapse probability levels.
Results
The enrolled patients (n = 133) had been followed for a median of 3 years (range 0.8–33 years) after AED discontinuation; 60 (45%) of them relapsed. Previous febrile seizures in childhood (hazard ratio HR 3.927; 95% confidence interval CI 1.403–10.988), a seizure‐free period on therapy of less than 2 years (HR 2.313; 95% CI 1.193–4.486), and persistent motor deficits (HR 4.568; 95% CI 1.412–14.772) were the clinical features associated with relapse risk in univariate analysis. Among these variables, only a seizure‐free period on therapy of less than 2 years was associated with seizure recurrence in multivariate analysis (HR 2.365; 95% CI 1.178–4.7444). Pharmacological control of epilepsy was restored in 82.4% of the patients who relapsed. In this population, the aforementioned prediction model showed an unsatisfactory accuracy.
Significance
A period of freedom from seizure on therapy of less than 2 years was the main predictor of seizure recurrence. The accuracy of the previously described prediction tool was low in this cohort, thus suggesting its cautious use in real‐world clinical practice.
Objective
Stereoelectroencephalography‐guided radiofrequency thermocoagulation (SEEG‐guided RF‐TC) aims to reduce seizure frequency by modifying epileptogenic networks through local thermocoagulative ...lesions. Although RF‐TC is hypothesized to functionally modify brain networks, reports of changes in functional connectivity (FC) following the procedure are missing. We evaluated, by means of SEEG recordings, whether variation in brain activity after RF‐TC is related to clinical outcome.
Methods
Interictal SEEG recordings from 33 patients with drug‐resistant epilepsy (DRE) were analyzed. Therapeutic response was defined as a >50% reduction in seizure frequency for at least 1 month following RF‐TC. Local (power spectral density PSD) and FC changes were evaluated in 3‐min segments recorded shortly before (baseline), shortly after, and 15 min after RF‐TC. The PSD and FC strength values after thermocoagulation were compared with baseline as well as between the responder and nonresponder groups.
Results
In responders, we found a significant reduction in PSD after RF‐TC in channels that were thermocoagulated for all frequency bands (p = .007 for broad, delta and theta, p <.001 for alpha and beta bands). However, we did not observe such PSD decrease in nonresponders. At the network level, nonresponders displayed a significant FC increase in all frequency bands except theta (broad, delta, beta band: p <.001; alpha band: p <.01), although responders showed a significant FC decrease in delta (p <.001) and alpha bands (p <.05). Nonresponders showed stronger FC changes with respect to responders exclusively in TC channels (broad, alpha, theta, beta: p >.05; delta: p = .001).
Significance
Thermocoagulation induces both local and network‐related (FC) changes in electrical brain activity of patients with DRE lasting for at least 15 min. This study demonstrates that the observed short‐term modifications in brain network and local activity significantly differ between responders and nonresponders and opens new perspectives for studying the longer‐lasting FC changes after RF‐TC.
Objective
Stereo‐electroencephalography (SEEG)‐guided radiofrequency thermocoagulation (RF‐TC) aims at modifying epileptogenic networks to reduce seizure frequency. High‐frequency oscillations ...(HFOs), spikes, and cross‐rate are quantifiable epileptogenic biomarkers. In this study, we sought to evaluate, using SEEG signals recorded before and after thermocoagulation, whether a variation in these markers is related to the therapeutic effect of this procedure and to the outcome of surgery.
Methods
Interictal segments of SEEG signals were analyzed in 38 patients during presurgical evaluation. We used an automatized method to quantify the rate of spikes, rate of HFOs, and cross‐rate (a measure combining spikes and HFOs) before and after thermocoagulation. We analyzed the differences both at an individual level with a surrogate approach and at a group level with analysis of variance. We then evaluated the correlation between these variations and the clinical response to RF‐TC and to subsequent resective surgery.
Results
After thermocoagulation, 19 patients showed a clinical improvement. At the individual level, clinically improved patients more frequently had a reduction in spikes and cross‐rate in the epileptogenic zone than patients without clinical improvement (p = .002, p = .02). At a group level, there was a greater decrease of HFOs in epileptogenic and thermocoagulated zones in patients with clinical improvement (p < .05) compared to those with no clinical benefit. Eventually, a significant decrease of all the markers after RF‐TC was found in patients with a favorable outcome of resective surgery (spikes, p = .026; HFOs, p = .03; cross‐rate, p = .03).
Significance
Quantified changes in the rate of spikes, rate of HFOs, and cross‐rate can be observed after thermocoagulation, and the reduction of these markers correlates with a favorable clinical outcome after RF‐TC and with successful resective surgery. This may suggest that interictal biomarker modifications after RF‐TC can be clinically used to predict the effectiveness of the thermocoagulation procedure and the outcome of resective surgery.
The study assessed the clinical response to add‐on brivaracetam (BRV) in real‐world practice by means of time‐to‐baseline seizure count methodology. Patients with focal epilepsy who were prescribed ...add‐on BRV were identified. Primary endpoint was the time‐to‐baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three‐hundred eighty‐seven patients were included. The overall median time‐to‐baseline seizure count was 150 (95% confidence interval CI = 130‐175) days. The median time‐to‐baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV‐naive patients, 126 (95% CI = 105‐150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128‐291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio adjHR = 1.07, 95% CI = 1.02‐1.13, P = .009) and baseline monthly seizure frequency (adjHR = 1.004, 95% CI = 1.001‐1.008, P = .028) were independently associated with the primary endpoint. Add‐on BRV improved seizure control in LEV‐naive and LEV‐prior patients. The time‐to‐baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.
•BRV proved to be useful and safe for the treatment of status epilepticus.•Time to seizures resolution appears shorter when it is administered in the early phases of status epilepticus.•The use of ...the BRV within 6 h from SE onset was independently associated to an early seizures’ resolution.•No severe treatment emergent adverse events were observed.
to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE).
a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6 h after BRV administration.
56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100 mg (range 50−300 mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6 h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39–202; p = 0.002). No severe treatment emergent adverse events were observed.
BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.
Introduction
In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on ...refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST).
Methods
BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1–2 (early add-on) and ≥ 3 (late add-on) prior antiseizure medications.
Results
A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12 months was 125 (100–200) mg in the early add-on group and 200 (100–200) in the late add-on group (
p
< 0.001). Sustained seizure response was reached by 97/161 (60.3%) of patients in the early add-on group and 286/833 (34.3%) of patients in the late add-on group (
p
< 0.001). Sustained seizure freedom was achieved by 51/161 (31.7%) of patients in the early add-on group and 91/833 (10.9%) of patients in the late add-on group (
p
< 0.001). During the 1-year study period, 29 (16.5%) patients in the early add-on group and 241 (28.3%) in the late add-on group discontinued BRV (
p
= 0.001). Adverse events were reported by 38.7% and 28.5% (
p
= 0.017) of patients who received BRV as early and late add-on treatment, respectively.
Conclusion
Brivaracetam was effective and well tolerated both as first add-on and late adjunctive treatment in patients with focal epilepsy.
BackgroundThe use of CD20-depleting monoclonal antibodies has shown to improve the long-term outcome of patients with anti-leucine-rich glioma-inactivated protein 1 antibodies (anti-LGI1-Abs) ...encephalitis after first-line immunotherapy, but currently predictive markers of treatment response and disease activity are lacking. Case presentationA 75-year-old man presented cognitive impairment and faciobrachial dystonic seizures (FBDS), with mild abnormalities at electroencephalography (EEG), normal brain magnetic resonance and cerebrospinal fluid (CSF) analysis. Anti-LGI1-Abs were detected in serum and CSF, and corticosteroids and intravenous immunoglobulins were administered. Despite partial cognitive improvement, 18F-fluoridesoxyglucose-positron emission tomography (18F-FDG-PET) showed the persistence of temporo-mesial hypermetabolism, and FBDS were still detected by long-term monitoring video EEG (LTMV EEG). Rituximab was therefore administered with FBDS disappearance, further cognitive improvement, and resolution of 18F-FDG-PET temporo-mesial hypermetabolism. ConclusionsOur experience supports the use of 18F-FDG-PET and LTMVEEG as useful tools to measure disease activity, evaluate treatment response and guide therapeutic decisions in the long-term management of anti-LGI1-antibody encephalitis.
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