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1.
Epilepsia ; 65(2): 456-472, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38052481

RESUMEN

OBJECTIVE: There are few comparative data on the third-generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives. METHODS: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add-on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan-Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models. RESULTS: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)-naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.29) and PER groups (HR = 1.64, 95% CI = 1.06-2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71-16.61), as well as PER-treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05-2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] = .08, 95% CI = .01-.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV-naïve (OR = 10.32, 95% CI = 1.55-68.78) versus men. PER (OR = 6.93, 95% CI = 3.32-14.44) and BRV in LEV-naïve patients (OR = 6.80, 95% CI = 2.64-17.52) had a higher chance of AEs than LCM. SIGNIFICANCE: Comparative evidence from real-world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics.


Asunto(s)
Epilepsias Parciales , Epilepsia , Nitrilos , Piridonas , Masculino , Adulto , Humanos , Femenino , Anticonvulsivantes/efectos adversos , Epilepsias Parciales/tratamiento farmacológico , Estudios Retrospectivos , Levetiracetam/uso terapéutico , Lacosamida/uso terapéutico , Epilepsia/tratamiento farmacológico , Pirrolidinonas/uso terapéutico , Resultado del Tratamiento
2.
Epilepsia ; 64(8): 2094-2107, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37114853

RESUMEN

OBJECTIVE: This study was undertaken to evaluate perampanel (PER) when used under real-world conditions to treat people with idiopathic generalized epilepsy (IGE) included in the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study. METHODS: The multinational, retrospective, pooled analysis PERMIT explored the use of PER in people with focal and generalized epilepsy treated in clinical practice across 17 countries. This subgroup analysis included PERMIT participants with IGE. Time points for retention and effectiveness measurements were 3, 6, and 12 months (last observation carried forward, defined as "last visit," was also applied to effectiveness). Effectiveness was evaluated by seizure type (total seizures, generalized tonic-clonic seizures [GTCS], myoclonic seizures, absence seizures) and included ≥50% responder rate and seizure freedom rate (defined as no seizures since at least the previous visit). Safety/tolerability was monitored throughout PER treatment and evaluated by documenting the incidence of adverse events (AEs), including psychiatric AEs and those leading to treatment discontinuation. RESULTS: The Full Analysis Set included 544 people with IGE (51.9% women, mean age = 33.3 years, mean epilepsy duration = 18.1 years). At 3, 6, and 12 months, 92.4%, 85.5%, and 77.3% of participants were retained on PER treatment, respectively (Retention Population, n = 497). At the last visit, responder and seizure freedom rates were, respectively, 74.2% and 54.6% (total seizures), 81.2% and 61.5% (GTCS), 85.7% and 66.0% (myoclonic seizures), and 90.5% and 81.0% (absence seizures) (Effectiveness Population, n = 467). AEs occurred in 42.9% of patients and included irritability (9.6%), dizziness/vertigo (9.2%), and somnolence (6.3%) (Tolerability Population, n = 520). Treatment discontinuation due to AEs was 12.4% over 12 months. SIGNIFICANCE: This subgroup analysis of the PERMIT study demonstrated the effectiveness and good tolerability of PER in people with IGE when administered under everyday clinical practice conditions. These findings are in line with clinical trial evidence, supporting PER's use as broad-spectrum antiseizure medication for the treatment of IGE.


Asunto(s)
Epilepsias Mioclónicas , Epilepsia Tipo Ausencia , Epilepsia Generalizada , Adulto , Femenino , Humanos , Masculino , Anticonvulsivantes/uso terapéutico , Quimioterapia Combinada , Epilepsias Mioclónicas/tratamiento farmacológico , Epilepsia Tipo Ausencia/tratamiento farmacológico , Epilepsia Generalizada/tratamiento farmacológico , Inmunoglobulina E/uso terapéutico , Piridonas/uso terapéutico , Estudios Retrospectivos , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Resultado del Tratamiento
3.
Epilepsy Behav ; 125: 108391, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34742034

RESUMEN

INTRODUCTION: Migraine is a common comorbidity in patients with epilepsy. Considering the proven associations and the common pathophysiological features linking epilepsy and migraine, some anti-seizure medications (ASMs) have been considered as a treatment for both disorders. This study aimed at assessing both the effectiveness of perampanel (PER) on epileptic seizures and migraine attacks in patients with epilepsy and comorbid migraine, as well as the reduction in the monthly mean rate usage of rescue migraine medications. METHODS: This observational, multi-centre study included adult patients with epilepsy and comorbid migraine who started PER to better control epileptic seizures and who were followed up for 12 months. RESULTS: Thirty-one patients were included (mean age 40.13 ±â€¯13.13 years; 67.0% female). At the 12-month follow-up visit, 27 patients were continuing PER concomitantly with 1 (45.2%) or 2 ASMs (54.8%). A significant reduction in epileptic seizures, migraine attacks, and the monthly use of rescue migraine medications between baseline and both 6- and 12-month follow-up visits was documented. CONCLUSION: PER demonstrated good effectiveness in reducing both epileptic seizures and migraine attacks in patients with comorbid epilepsy and migraine. Future studies with possibly larger samples are needed to evaluate the efficacy of PER in migraine other than epilepsy.


Asunto(s)
Epilepsia , Trastornos Migrañosos , Adulto , Anticonvulsivantes/uso terapéutico , Comorbilidad , Epilepsia/complicaciones , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/epidemiología , Nitrilos , Piridonas/uso terapéutico
4.
Epilepsy Behav ; 121(Pt A): 108069, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34077902

RESUMEN

INTRODUCTION: The main of the present study was to assess the effectiveness and tolerability of perampanel (PER) in association with 1 or 2 concomitant antiseizure medications (ASMs) in patients with epilepsy throughout a follow-up period of 24 months or longer in a real-world setting. METHODS: This retrospective, observational, multi-center study collected data from both underage (<18 years old) and adult patients who had started PER in association with 1 or 2 ASMs. Only patients who had started PER and were followed up for at least 24 months were included. Response to treatment was analyzed at the 24-, 36-, and 48-month visits by considering the last visit undergone by patients. Subgroup analyses were performed according to age, gender, and epilepsy type and patients were categorized following PER treatment in concomitance with 1 or 2 ASMs to evaluate the factors affecting the achievement of seizure freedom (SF) at the 24-month FU. RESULTS: Ninety-four patients were included (mean age 36.89 years; 51.1% female). At the 24-month follow-up visit, 90 (95.74%) patients were still receiving PER concomitantly with 1 or 2 ASMs. The mean PER dose was 6.02 mg/day and SF was achieved by 33 (35.1%) patients. A significantly higher SF rate was found in patients who had started PER with only 1 ASM when compared to those who had started PER with 2 concomitant ASMs. Effectiveness was maintained also in the subgroups of patients with a 36- or 48-month follow-up visit. Adult patients had a higher final daily dosage of PER than underage patients. Logistic regression found that the lowest number of previously failed ASMs was associated with a higher SF rate (p = 0.036). CONCLUSION: Perampanel demonstrated a good effectiveness in association with 1 or 2 ASMs in both pediatric and adult patients, without having to use a high dose of the drug. The possibility to present SF was higher when PER was added early. Finally, the maintenance of effectiveness was observed also in the subgroups of patients with a follow-up of 36 and 48 months.


Asunto(s)
Anticonvulsivantes , Epilepsia , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Niño , Epilepsia/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Nitrilos , Piridonas/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
5.
Neurol Sci ; 42(4): 1531-1534, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33190197

RESUMEN

BACKGROUND: Anti-myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are new emerging diseases with heterogeneous course, treatment, response, and prognosis. CASE REPORT: We herein present 2 cases with antibodies to MOG, one with a cerebellar/brainstem monophasic syndrome which partially improved after treatment, and the other with an optic neuritis onset then relapsed with cortical encephalitis and presented a subsequent complete recovery. We further discuss elements possibly associated with disease heterogeneity and influencing treatment choices. CONCLUSIONS: MOGAD is an extremely variable disease which can relapse and accumulate disability over time. An early diagnosis and correct timely treatment is fundamental to improve clinical outcome.


Asunto(s)
Enfermedades Desmielinizantes , Encefalitis , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica , Anticuerpos , Autoanticuerpos , Enfermedades Desmielinizantes/metabolismo , Humanos
6.
Epilepsy Behav ; 98(Pt A): 139-144, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31374469

RESUMEN

Cognitive dysfunctions are frequent in patients with epilepsy. This comorbidity significantly alters their quality of life and plays an important role in their therapeutic management. Perampanel is a noncompetitive antagonist of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors and is considered a new generation AED (antiepileptic drug) with limited impact on cognitive functions.The aims of this study were to evaluate the efficacy of perampanel as first add-on therapy and its impact on cognitive functions and quality of life in patients with epilepsy followed for 6 months at the Neurology Division of "A. Cardarelli" Hospital in Naples (Italy).


Asunto(s)
Anticonvulsivantes/farmacología , Disfunción Cognitiva/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Piridonas/farmacología , Calidad de Vida , Adulto , Disfunción Cognitiva/etiología , Quimioterapia Combinada , Epilepsia/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitrilos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
7.
Neurol Sci ; 36(12): 2263-8, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26209931

RESUMEN

Thrombocytopenia is a well-described adverse event of several disease-modifying therapies (DMT) in multiple sclerosis (MS). On the other hand, an increased prevalence of MS has been reported in patients with immune thrombocytopenia. In this retrospective, cross-sectional, case-control study we evaluated in a heterogeneous MS cohort: (1) the prevalence of thrombocytopenia in comparison with sex- and age-matched controls; (2) the relationship between thrombocytopenia and patients' demographic, clinical characteristics; (3) the risk for thrombocytopenia in relation to DMT. 187 consecutive MS patients [51 males, mean age (±SD) 44.5 ± 10.7 years] and 200 controls (56 males, mean age 45.5 ± 12 years) were included. Thrombocytopenia was defined as platelet count lower than normal laboratory values (130-400 × 10(9)/L). The prevalence of thrombocytopenia was significantly higher in MS patients than in controls (7 vs. 2.5 %, p = 0.04). Thrombocytopenia was present only in relapsing-remitting MS cases, and significantly associated with lower EDSS (p = 0.002) and with a trend for shorter disease duration (p = 0.06). It was more frequent in patients on high-dose interferon-ß therapy compared with those on low-dose interferon-ß therapy, other therapies or untreated patients (p = 0.02). High-dose interferon-ß therapy was associated with more than eightfold increase in the risk for thrombocytopenia (odds ratio 8.60, 95 % confidence interval: 1.01-74.48 adjusted for EDSS, disease duration and type of disease). The prevalence of thrombocytopenia was increased in MS patients treated with DMT. High-dose interferon-ß therapy is the variable most strongly associated with thrombocytopenia.


Asunto(s)
Inmunoterapia , Interferón beta/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológico , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Inmunoterapia/métodos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico , Estudios Retrospectivos , Riesgo , Trombocitopenia/complicaciones , Trombocitopenia/diagnóstico , Resultado del Tratamiento
9.
Eur Neurol ; 73(3-4): 233-237, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25823947

RESUMEN

BACKGROUND/AIMS: The relationship between multiple sclerosis (MS) and anemia has not been clarified sufficiently. In this retrospective, cross-sectional, case-control study we evaluated in MS patients: (1) prevalence of anemia relative to sex- and age-matched controls; (2) relationships between patients' demographic, clinical and drug-related characteristics and anemia; (3) effect of anemia on the risk of developing MS. METHODS: 187 consecutive MS patients (51 males, mean age (±SD) 44.5 ± 10.7 years) and 200 controls (56 males, mean age 45.5 ± 12 years) were included in the study. Anemia was defined as hemoglobin <12 g/dl for females and <13 g/dl for males. RESULTS: There was a significant difference in the prevalence of anemia between MS patients and controls (35 (18.7%) and 19 (9.5%), respectively, p = 0.009). We did not find any association between patients' characteristics and anemia. The occurrence of anemia increased more than twice the risk of developing MS (odds ratio: 2.19, 95% confidence interval 1.19-4.0). CONCLUSION: Our study showed a consistent association between anemia and MS.


Asunto(s)
Anemia/complicaciones , Anemia/epidemiología , Esclerosis Múltiple/epidemiología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Estudios Retrospectivos , Riesgo
10.
J Spinal Cord Med ; 38(4): 559-62, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25343982

RESUMEN

CONTEXT: Copper deficiency myelopathy represents an often underdiagnosed, acquired neurological syndrome, clinically characterized by posterior column dysfunction. The main causes of copper deficiency are bariatric surgery, increased consumption of zinc, and malabsorption. However, even after a careful history taking and extensive laboratory researches, the etiology of copper deficiency remains undetermined in a significant percentage of cases. Patients affected by copper deficiency myelopathy usually present with sensory ataxia due to dorsal column dysfunction and sometimes with mild leg spasticity. In such patients, spinal cord magnetic resonance imaging (MRI) may show hyperintense lesions in T2-weighted sequences involving the posterior columns of cervical and thoracic cord. These MRI findings are not distinguishable from those of subacute combined degeneration associated with vitamin B12 deficiency. FINDINGS: Here, we describe two patients with gait ataxia and sensory symptoms in which a diagnosis of copper deficiency myelopathy was made. Both patients showed a significant clinical, neuroradiological, and neurophysiological improvement after proper supplementation therapy. CONCLUSION: The patients herein described underline the importance to include serum copper and ceruloplasmin levels as part of the myelopathy diagnostic workup, especially in the cases of otherwise unexplained subacute myelopathy involving the posterior columns. Since copper deficiency myelopathy is a progressive syndrome, early diagnosis is mandatory in order to promptly provide a proper supplementation therapy and, thus, prevent an irreversible neurological damage.


Asunto(s)
Cobre/deficiencia , Enfermedades de la Médula Espinal/diagnóstico , Femenino , Humanos , Persona de Mediana Edad
11.
J Stroke Cerebrovasc Dis ; 23(3): e221-7, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24418315

RESUMEN

BACKGROUND: Approximately 10%-14% of ischemic strokes occur in young adults. AIMS: To investigate risk factors and etiologies of strokes of young adults admitted to the "stroke unit" of Policlinico "Gemelli" of Rome from December 2005 to January 2013. METHODS: In all, 150 consecutive patients younger than 50 years diagnosed with ischemic stroke were enrolled. Clinical evaluation consisted of a complete neurologic examination and the National Institutes of Health Stroke Scale. Diagnostic workup consisted of anamnesis, extensive laboratory, radiologic, and cardiologic examination. Stroke etiologies were classified according to the Trial of Org 10172 in Acute Stroke Treatment. RESULTS: Patients' mean age was 41 ± 8.0 years. The most common risk factors were dyslipidemia (52.7%), smoking (47.3%), hypertension (39.3%), and patent foramen ovale (PFO, 32.8%). Large-artery atherosclerosis was diagnosed as the cause of stroke in 17 patients (11.3%). Cardioembolism was presumed in 36 patients (24%), most of them presented a PFO at transesophageal echocardiography. Small-vessel occlusion was diagnosed in 12 patients (8%); all of them were hypertensive and most of them presented additional risk factors. Forty-one patients (27.3%) presented a stroke of other determined etiology and 44 (29.3%) presented a stroke of undetermined etiology. The 3-year survival was 96.8% and recurrent strokes occurred in only 3 cases. CONCLUSIONS: Traditional vascular risk factors are also very common in young adults with ischemic stroke, but such factors increase the susceptibility to stroke dependent to other causes as atherosclerosis and small-artery occlusion represent less than 20% of cases. Prognosis quoadvitam is good, being characterized by low mortality and recurrence rate.


Asunto(s)
Isquemia Encefálica/etiología , Accidente Cerebrovascular/etiología , Adulto , Factores de Edad , Aterosclerosis/complicaciones , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidad , Dislipidemias/complicaciones , Embolia/complicaciones , Femenino , Foramen Oval Permeable/complicaciones , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Ciudad de Roma , Fumar/efectos adversos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Tasa de Supervivencia , Factores de Tiempo
12.
J Neurol Sci ; 462: 123106, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38925069

RESUMEN

INTRODUCTION: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy. Nevertheless, there is limited evidence regarding the clinical profile of antiseizure medications (ASMs) in PSE. This study aims to evaluate the 12-month effectiveness and tolerability of perampanel (PER) used as only add-on treatment in patients with PSE in a real-world setting. METHODS: We performed a subgroup analysis of PSE patients included in a previous retrospective, longitudinal, multicentre observational study on adults. Treatment discontinuation, seizure frequency and adverse events were collected at 3, 6 and 12 months. Sub-analyses by early (≤1 previous ASM) or late PER add-on were also conducted. RESULTS: Our analysis included 56 individuals with PSE, characterized by varying initial treatment modalities and timeframes relative to disease onset. We found notable retention rates (92.8%, 83.7%, and 69% at 3, 6, and 12 months), with treatment withdrawal mainly due to poor tolerability. One year after PER introduction, seizure frequency significantly reduced, with a responder rate (≥50% reduction) of 83.9% and a seizure-free rate of 51.6%. Adverse events occurred in 25 (46.3%) patients, mainly dizziness, irritability, and behavioural disorders. No major statistical differences were found between early (30 patients, 53.6%) and late add-on groups, except for a higher 6-month responder rate in the early add-on group. CONCLUSION: Adjunctive PER was effective and well-tolerated in patients with PSE in a real-world setting. Perampanel demonstrated good efficacy and safety as both early and late add-on treatment, making it a compelling option for this unique patient population.

13.
J Stroke Cerebrovasc Dis ; 22(7): e254-5, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23410685

RESUMEN

Fabry disease is an inborn error of glycosphingolipid catabolism caused by deficient activity of the lysosomal exoglycohydrolase α-galactosidase A. It has an X-linked inheritance and occurs in all ethnic groups, with an incidence of 1 in 40,000 in the general population. The incidence of cerebrovascular accidents in patients affected by Fabry disease is much higher than in the general population. Moreover, there is a greater prevalence of hypertension, cardiac disease, and renal disease in patients affected by Fabry disease that have suffered a stroke. Here we present the case of a paucisymptomatic young man affected by Fabry disease and treated with enzyme replacement therapy who was admitted for hemorrhagic stroke.


Asunto(s)
Hemorragia Cerebral/complicaciones , Enfermedad de Fabry/complicaciones , Accidente Cerebrovascular/complicaciones , Adulto , Humanos , Masculino
14.
J Neurol Sci ; 455: 122797, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-37976793

RESUMEN

INTRODUCTION: Drug management of epilepsy in the elderly presents unique but data on this population are scarce. This study aimed to assess the effectiveness and tolerability of perampanel (PER) used as only add-on to a background anti-seizure medication (ASM) in the elderly in a real-world setting. METHODS: We performed a subgroup analysis of patients aged ≥65 years included in a previous 12-month multicenter study on adults. Treatment discontinuation, seizure frequency, and adverse events were recorded at 3, 6 and 12 months after PER introduction. Sub-analyses by early (≤1 previous ASM) or late PER add-on were also conducted. RESULTS: The sample included 65 subjects (mean age: 75.7 ± 7.2 years), with mainly focal (73.8%) epilepsy. The mean PER daily dose was ≈4 mg during all follow-up. Retention rates at 3, 6, and 12 months were 90.5%, 89.6%, and 79.4%ly. The baseline median normalized per 28-day seizure number significantly decreased at 3-, 6- and 12-month visits. One year after PER introduction, the responder rate (≥50% reduction in baseline seizure frequency) was 89.7%, with a seizure freedom rate of 72.4%. Adverse events occurred in 22 (34.9%) patients with dizziness and irritability being the most frequent. No major differences between early (41 patients, 63.1%), and late add-on groups were observed. CONCLUSION: Adjunctive PER was effective and well-tolerated when used as only add-on treatment in elderly people with epilepsy in clinical practice, thus representing a suitable therapeutic option in this age category.


Asunto(s)
Anticonvulsivantes , Epilepsia , Anciano , Anciano de 80 o más Años , Humanos , Anticonvulsivantes/efectos adversos , Quimioterapia Combinada , Epilepsia/tratamiento farmacológico , Estudios Retrospectivos , Convulsiones/tratamiento farmacológico , Resultado del Tratamiento , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto
15.
Seizure ; 108: 72-80, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37104972

RESUMEN

OBJECTIVE: Nearly half of people with epilepsy (PWE) are expected to develop seizure clusters (SC), with the subsequent risk of hospitalization. The aim of the present study was to evaluate the use, effectiveness and safety of intravenous (IV) brivaracetam (BRV) in the treatment of SC. METHODS: Retrospective multicentric study of patients with SC (≥ 2 seizures/24 h) who received IV BRV. Data collection occurred from January 2019 to April 2022 in 25 Italian neurology units. Primary efficacy outcome was seizure freedom up to 24 h from BRV administration. We also evaluated the risk of evolution into Status Epilepticus (SE) at 6, 12 and 24 h after treatment initiation. A Cox regression model was used to identify outcome predictors. RESULTS: 97 patients were included (mean age 62 years), 74 (76%) of whom had a history of epilepsy (with drug resistant seizures in 49% of cases). BRV was administered as first line treatment in 16% of the episodes, while it was used as first or second drug after benzodiazepines failure in 49% and 35% of episodes, respectively. On the one hand, 58% patients were seizure free at 24 h after BRV administration and no other rescue medications were used in 75 out of 97 cases (77%) On the other hand, SC evolved into SE in 17% of cases. A higher probability of seizure relapse and/or evolution into SE was observed in patients without a prior history of epilepsy (HR 2.0; 95% CI 1.03 - 4.1) and in case of BRV administration as second/third line drug (HR 3.2; 95% CI 1.1 - 9.7). No severe treatment emergent adverse events were observed. SIGNIFICANCE: In our cohort, IV BRV resulted to be well tolerated for the treatment of SC and it could be considered as a treatment option, particularly in case of in-hospital onset. However, the underlying etiology seems to be the main outcome predictor.


Asunto(s)
Epilepsia Generalizada , Epilepsia , Estado Epiléptico , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Anticonvulsivantes/efectos adversos , Resultado del Tratamiento , Epilepsia/tratamiento farmacológico , Epilepsia Generalizada/tratamiento farmacológico , Pirrolidinonas/efectos adversos , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/inducido químicamente , Quimioterapia Combinada
16.
Epilepsia Open ; 2022 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-36082380

RESUMEN

OBJECTIVE: Perampanel (PER) is indicated as adjunctive antiseizure medication (ASM) in adolescents and adults with epilepsy. Data from clinical trials show good efficacy and tolerability, while limited information is available on the routine clinical use of PER, especially when used as only add-on treatment. METHODS: we performed an observational, retrospective, multicenter study on people with focal or generalized epilepsy aged >12 years, consecutively recruited from 52 Italian epilepsy centers. All patients received PER as the only add-on treatment to a background ASM according to standard clinical practice. Retention rate, seizure frequency and adverse events were recorded at 3, 6 and 12 months after PER introduction. Sub-analyses by early or late use of PER and by concomitant ASM were also conducted. RESULTS: 503 patients were included (age 36.5±19.9 years). Eighty-one per cent had focal epilepsy. Overall, the retention rate was very high in the whole group (89% at 12 months) according with efficacy measures. No major differences were observed in the sub-analyses, although patients who used PER as early add-on, as compared with late add-on, more often reached early seizure freedom at 3 months follow-up (66% vs. 53%, p=0.05). Treatment-emergent adverse events occurred in 25%, far less commonly than in PER randomized trials. SIGNIFICANCE: this study confirms the good efficacy and safety of PER for focal or generalized epilepsy in real-life conditions. We provide robust data about its effectiveness as only add-on treatment even in patients with a long-standing history of epilepsy and previously treated with many ASMs.

17.
J Clin Immunol ; 31(2): 155-66, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21063901

RESUMEN

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited disease, and although strongly suggested, a contribution of inflammation to its pathogenesis has never been demonstrated. In FSHD patients, we found by immunohistochemistry inflammatory infiltrates mainly composed by CD8(+) T cells in muscles showing hyperintensity features on T2-weighted short tau inversion recovery magnetic resonance imaging (T2-STIR-MRI) sequences. Therefore, we evaluated the presence of circulating activated immune cells and the production of cytokines in patients with or without muscles showing hyperintensity features on T2-STIR-MRI sequences and from controls. FSHD patients displaying hyperintensity features in one or more muscles showed higher CD8(+)pSTAT1(+), CD8(+)T-bet(+) T cells and CD14(+)pSTAT1(+), CD14(+)T-bet(+) cells percentages and IL12p40, IFNγ and TNFα levels than patients without muscles displaying hyperintense features and controls. Moreover, the percentages of CD8(+)pSTAT1(+), CD8(+)T-bet(+) and CD14(+)pSTAT1(+) cells correlated with the proportion of muscles displaying hyperintensity features at T2-STIR sequences. These data indicate that circulating activated immune cells, mainly CD8(+) T cells, may favour FSHD progression by promoting active phases of muscle inflammation.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Imagen por Resonancia Magnética , Distrofia Muscular Facioescapulohumeral/inmunología , Distrofia Muscular Facioescapulohumeral/patología , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Citocinas/biosíntesis , Femenino , Humanos , Inflamación , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Distrofia Muscular Facioescapulohumeral/complicaciones , Miositis/diagnóstico , Miositis/etiología , Miositis/inmunología , Miositis/patología , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/metabolismo , Índice de Severidad de la Enfermedad , Proteínas de Dominio T Box/metabolismo
19.
Seizure ; 86: 70-76, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33561784

RESUMEN

PURPOSE: to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE). METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Asunto(s)
Estado Epiléptico , Anticonvulsivantes/uso terapéutico , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Pirrolidinonas/efectos adversos , Estudios Retrospectivos , Estado Epiléptico/tratamiento farmacológico , Resultado del Tratamiento
20.
Epileptic Disord ; 22(3): 309-316, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32540833

RESUMEN

Perampanel (PER) and brivaracetam (BRV) are third-generation antiseizure medications. The aim of the present retrospective, double-centre study was to compare the effectiveness and tolerability between PER and BRV in adult patients with epilepsy. We reviewed the clinical charts of patients affected by epilepsy, admitted to the Epilepsy Centre at the University Hospital of Rome "Tor Vergata" and the Cardarelli Hospital in Naples, who started BRV or PER as add-on treatment for controlling seizures with a follow-up of 12 months. Seizure freedom, >50% seizure reduction, retention rate, and adverse events reported during follow-up were compared between the two drugs. Moreover, we considered the effects of both drugs in specific subsets of patients: age ≥60 years, male or female, in patients with genetic generalized epilepsy, and considering previous treatment with levetiracetam (LEV). Forty-three patients treated with BRV and 64 patients treated with PER were included in this study and followed at both sites for 12 months. Similar effectiveness was observed between BRV and PER, with similar rates of seizure freedom (30% vs 31%) and >50% seizure reduction (32% vs 34%) during follow-up. Moreover, PER and BRV discontinuation rates, due to ineffectiveness or adverse events, were similar. Groups of patients who started BRV or PER as first add-on treatments were also compared but no differences in effectiveness or tolerability were identified. Lastly, BRV was shown to be more effective in patients who were not previously treated with LEV. This retrospective study reveals comparable effectiveness and tolerability between PER and BRV also when used as first add-on treatments, in patients with epilepsy.


Asunto(s)
Anticonvulsivantes/farmacología , Evaluación de Resultado en la Atención de Salud , Piridonas/farmacología , Pirrolidinonas/farmacología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Nitrilos , Piridonas/administración & dosificación , Piridonas/efectos adversos , Pirrolidinonas/administración & dosificación , Pirrolidinonas/efectos adversos , Estudios Retrospectivos , Adulto Joven
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