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OBJECTIVE: Women of childbearing age with juvenile absence epilepsy (JAE) face treatment challenges due to limited access to safe and effective anti-seizure medications (ASMs). In a previous study we compared the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) in women with idiopathic generalized epilepsy (IGE), highlighting a superiority of LEV in juvenile myoclonic epilepsy. In this study, we specifically reanalyzed, through a Bayesian approach and by expanding the previously published cohort, the comparative effectiveness of these ASMs as initial monotherapy in JAE. METHODS: We conducted a multicenter, retrospective, comparative effectiveness study on women of childbearing age diagnosed with JAE and prescribed LEV or LTG as the initial ASM. Inverse probability treatment weighting (IPTW) Bayesian Cox proportional hazard models were employed to evaluate treatment failure (TF) due to ineffectiveness and ASM retention. The patients' center of provenance and year of prescription were considered as random effect factors. Posterior probabilities and relative log-risk distribution were computed, and the distribution of posterior draws was analyzed to assess the evidence supporting LTG superiority over LEV. RESULTS: Of 123 patients, those treated with LTG (n = 67) demonstrated lower TF and higher ASM retention than those treated with LEV (n = 56), with the IPTW-weighted Bayesian Cox proportional hazards model showing a 99.2% posterior probability of LTG being superior on TF and a 99.5% probability on ASM retention. Additional analyses on ≥50% and ≥75% seizure reduction through IPTW-weighted Bayesian logistic regression largely confirmed these findings, whereas the two ASMs did not show evident differences in terms of seizure freedom. The two ASMs showed comparable safety profiles, with only a minority of patients discontinuing treatment due to side effects. SIGNIFICANCE: Bayesian reanalysis supports LTG as first-line monotherapy for JAE in women of childbearing age, emphasizing the importance of individualized treatment strategies in women with IGE. This study underscores the value of Bayesian methods in refining clinical research and treatment decisions.
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BACKGROUND AND OBJECTIVES: To investigate the predictors of seizure recurrence in women of childbearing age with idiopathic generalized epilepsy (IGE) who switched from valproate (VPA) to alternative antiseizure medications (ASMs) and compare the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) as VPA alternatives after switch. METHODS: This multicenter retrospective study included women of childbearing age diagnosed with IGE from 16 epilepsy centers. Study outcomes included worsening or recurrence of generalized tonic-clonic seizure (GTCS) at 12 months and 24 months after the switch from VPA to an alternative ASM. The comparative effectiveness of LEV and LTG as alternative ASM following VPA discontinuation was assessed through inverse probability treatment-weighted (IPTW) Cox regression analysis. RESULTS: We included 426 women with IGE, with a median (interquartile range) age at VPA switch of 24 (19-30) years and a median VPA dosage of 750 (500-1,000) mg/d. The most common reason for VPA switch was teratogenicity concern in 249 women (58.6%), and the most common ASM used in place of VPA was LEV in 197 (46.2%) cases, followed by LTG in 140 (32.9%). GTCS worsening/recurrence occurred in 105 (24.6%) and 139 (32.6%) women at 12 and 24 months, respectively. Catamenial worsening of seizures, higher VPA dosage during switch, multiple seizure types, and shorter duration of GTCS freedom before switch were independent predictors of GTCS recurrence or worsening at 12 months according to mixed multivariable logistic regression analysis. After internal-external validation through 16 independent cohorts, the model showed an area under the curve of 0.71 (95% CI 0.64-0.77). In the subgroup of 337 women who switched to LEV or LTG, IPTW Cox regression analysis showed that LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG (adjusted hazard ratio 0.59, 95% CI 0.40-0.87, p = 0.008) during the 24-month follow-up. DISCUSSION: Our findings can have practical implications for optimizing counselling and treatment choices in women of childbearing age with IGE and may help clinicians in making informed treatment decisions in this special population of patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with IGE switching from VPA, LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG.
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Epilepsia Generalizada , Ácido Valproico , Humanos , Feminino , Ácido Valproico/uso terapêutico , Estudos Retrospectivos , Anticonvulsivantes/uso terapêutico , Epilepsia Generalizada/tratamento farmacológico , Convulsões/tratamento farmacológico , Levetiracetam/uso terapêutico , Lamotrigina/uso terapêutico , Imunoglobulina E/uso terapêuticoRESUMO
Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.
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Epilepsia Generalizada , Epilepsia , Gravidez , Humanos , Feminino , Topiramato/efeitos adversos , Anticonvulsivantes/efeitos adversos , Teratogênicos/toxicidade , Estudos Retrospectivos , Estudos de Coortes , Frutose/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Levetiracetam/efeitos adversos , Imunoglobulina E/uso terapêuticoRESUMO
OBJECTIVE: This study aimed to explore the effectiveness of brivaracetam (BRV) according to baseline seizure frequency and past treatment history in subjects with focal epilepsy who were included in the Brivaracetam Add-On First Italian Network Study (BRIVAFIRST). METHODS: BRIVAFIRST was a 12-month retrospective, multicenter study including adults prescribed adjunctive BRV. Study outcomes included sustained seizure response (SSR), sustained seizure freedom (SSF), and the rates of treatment discontinuation and adverse events (AEs). Baseline seizure frequency was stratified as <5, 5-20, and >20 seizures per month, and the number of prior antiseizure medications (ASMs) as <5 and ≥6. RESULTS: A total of 994 participants were included. During the 1-year study period, SSR was reached by 45.8%, 39.3%, and 22.6% of subjects with a baseline frequency of <5, 5-20, and >20 seizures per month (p < .001); the corresponding figures for the SSF were 23.4%, 9.8%, and 2.8% (p < .001). SSR was reached by 51.2% and 26.5% participants with a history of 1-5 and ≥6 ASMs (p < .001); the corresponding rates of SSF were 24.7% and 4.5% (p < .001). Treatment discontinuation due to lack of efficacy was more common in participants with >20 seizures compared to those with <5 seizures per month (25.8% vs. 9.3%, p < .001), and in participants with history of ≥6 prior ASMs compared to those with history of 1-5 ASMs (19.6% vs. 12.2%, p = .002). There were no differences in the rates of BRV withdrawal due to AEs and the rates of AEs across the groups of participants defined according to the number of seizures at baseline and the number of prior ASMs. SIGNIFICANCE: The baseline seizure frequency and the number of previous ASMs were predictors of sustained seizure frequency reduction with adjunctive BRV in subjects with focal epilepsy.
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Anticonvulsivantes , Epilepsias Parciais , Adulto , Humanos , Anticonvulsivantes/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Quimioterapia Combinada , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamente , Epilepsias Parciais/tratamento farmacológico , Pirrolidinonas/uso terapêuticoRESUMO
Importance: After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors' knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients. Objective: To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE. Design, Setting, and Participants: This was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription. Exposures: Levetiracetam or lamotrigine as initial monotherapy. Main Outcomes and Measures: Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy. Results: A total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95% CI, 0.59-0.99; P = .04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR, 0.47; 95% CI, 0.32-0.68; P < .001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95% CI, 0.65-1.23; P = .60). Conclusions and Relevance: Results of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.
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Anticonvulsivantes , Epilepsia , Adulto , Criança , Humanos , Feminino , Masculino , Levetiracetam/uso terapêutico , Lamotrigina/uso terapêutico , Estudos Retrospectivos , Estudos de Coortes , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Imunoglobulina E/uso terapêuticoRESUMO
BACKGROUND: Neurosyphilis-associated cognitive and behavioral impairment- historically coined as "general paralysis of the insane"- share clinical and neuroradiological features with the neurodegenerative disease spectrum, in particular Alzheimer's disease (AD). Anatomopathological similarities have been extensively documented, i.e., neuronal loss, fibrillary alterations, and local amyloid-ß deposition. Consequently, accurate classification and timely differential diagnosis may be challenging. OBJECTIVE: To describe clinical, bio-humoral, brain MRI, FDG-PET, and amyloid-PET features in cases of neurosyphilis with an AD-like phenotypical presentation, as well as clinical outcome in terms of response to antibiotic therapy. METHODS: We selected the studies comparing patients with AD and with neurosyphilis associated cognitive impairment, to investigate candidate biomarkers classifying the two neurological diseases. RESULTS: The neuropsychological phenotype of general paralysis, characterized by episodic memory impairment and executive disfunction, substantially mimics clinical AD features. Neuroimaging often shows diffuse or medial temporal cortical atrophy, thus contributing to a high rate of misdiagnosis. Cerebrospinal fluid (CSF)-based analysis may provide supportive diagnostic value, since increased proteins or cells are often found in neurosyphilis, while published data on pathophysiological AD candidate biomarkers are controversial. Finally, psychometric testing using cross-domain cognitive tests, may highlight a wider range of compromised functions in neurosyphilis, involving language, attention, executive function, and spatial ability, which are atypical for AD. CONCLUSION: Neurosyphilis should be considered a potential etiological differential diagnosis of cognitive impairment whenever imaging, neuropsychological or CSF features are atypical for AD, in order to promptly start antibiotic therapy and delay or halt cognitive decline and disease progression.
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Doença de Alzheimer , Disfunção Cognitiva , Doenças Neurodegenerativas , Neurossífilis , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Testes Neuropsicológicos , Fenótipo , Neurossífilis/diagnóstico por imagem , Antibacterianos/uso terapêutico , Proteínas tau/líquido cefalorraquidianoRESUMO
BACKGROUND: Chimeric Antigen Receptor (CAR) T cell therapies are innovative treatments against hematological malignancies, with increasing therapeutic indications. Despite their great efficacy, these therapies are hampered by high rates of neurotoxicity (immune effector cell-associated neurotoxicity (ICANS)). In the past few years, several risk factors have been associated with ICANS and grouped together in the attempt to build validated models able to predict neurologic complications. However, little is known about pre-existing neurologic conditions possibly related to the development of neurotoxicity. METHODS AND RESULTS: In our case series, including sixteen consecutive patients treated with CAR T cells, we observed that (i) neurotoxicity only occurred in the two patients who presented subtle clinical signs of frontal lobe impairment at baseline and (ii) neurologic manifestations of ICANS consisted of language disturbances and cortical frontal myoclonus, which were both manifestations of a frontal predominant dysfunction. DISCUSSION: Based on our experience, we suggest that a pre-existing frontal lobe impairment, even if at a subclinical level, may eventually drive to ICANS, which in turn shows symptoms compatible with a frontal encephalopathy. It is remarkable that this focal neurotoxicity involved the same CNS regions that were responsible of subtle neurological signs at baseline. Future studies on larger numbers of patients are needed to confirm the possible role of baseline frontal lobe dysfunction as a predictor of ICANS, in order to enhance efforts to safely deliver CAR T cell therapy.
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Imunoterapia Adotiva , Síndromes Neurotóxicas , Humanos , Imunoterapia Adotiva/efeitos adversos , Síndromes Neurotóxicas/etiologia , Pesquisa , Lobo FrontalRESUMO
Intravascular large B-cell lymphoma (IVLBCL) is a very rare form of extranodal lymphoma, characterized by the proliferation of neoplastic B cells within the lumen of small vessels. Due to its high aggressivity, for years the prognosis had been really poor with only anectodical cases of remission after traditional chemotherapy. More recently, new therapeutic protocols allowed a significant increase in overall survival. It can virtually involve every organ, being skin and central nervous system the most affected. The clinical presentation is often unspecific and insidious; therefore, diagnosis can be challenging. Tissue biopsy, in particular random deep skin biopsy, is the gold standard for definitive diagnosis. We describe the case of a 58-year-old woman with a previous diagnosis of myelofibrosis, who presented with a rapidly progressive neurological deterioration and a brain MRI suggestive of Progressive Multifocal Leukoencephalopathy. Due to the absence of BK and JC viruses in cerebrospinal fluid and the presence of severe myalgias and subcutaneous nodules, a skin and muscle biopsy was performed, allowing diagnosis of IVLBCL. We describe the diagnostic pitfalls of this case, briefly reviewing existing literature about IVLBCL.
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Leucoencefalopatia Multifocal Progressiva , Linfoma Difuso de Grandes Células B , Neoplasias Cutâneas , Feminino , Humanos , Pessoa de Meia-Idade , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Pele/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
Background: Functional connectivity (FC) studies showed that pharmaco-resistant mesial temporal lobe epilepsy (MTLE) affects not only the limbic system, but also several extra-limbic regions, including areas belonging to resting state networks. Less is known about FC in subjects with benign MTLE (i.e., sensitive to antiseizure medication, bMTLE). Aim and methods: We evaluated FC of hippocampus and amygdala in subjects with bMTLE, distinguished based on the epileptic focus lateralization. We enrolled 19 patients (10 with left and 9 with right bMTLE) and 10 age-matched healthy subjects. Connectivity was investigated at rest by using a seed-based regression analyses approach with four regions of interest (left and right hippocampus, left and right amygdala). Patients were also tested with a neuropsychological battery and their scores were correlated with fMRI data. Results and conclusions: Our study documented an asymmetrical disruption of FC in bMTLE, in relation to the side of the focus. Right subjects only exhibited limited altered connections, while left subjects-who performed worse in verbal memory tests-showed a wide bilateral hypoconnectivity of hippocampus and amygdala with areas belonging to language and memory network. The strength of FC between left limbic areas and language and memory network correlated with better performances in verbal memory tests. Moreover, we observed an increased FC with areas of default mode network, more pronounced in left subjects, a possible attempt to compensate cognitive deficit but without effectiveness.We believe that these findings could help to better characterize bMTLE, in which a dysfunction of limbic connectivity is detectable despite well-controlled epilepsy.
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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.
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The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32-56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy.
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Anticonvulsivantes , Epilepsias Parciais , Adulto , Anticonvulsivantes/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Epilepsias Parciais/tratamento farmacológico , Liberdade , Humanos , Pessoa de Meia-Idade , Pirrolidinonas/uso terapêutico , Convulsões/tratamento farmacológico , Resultado do TratamentoRESUMO
OBJECTIVE: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. METHODS: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), 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. RESULTS: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. SIGNIFICANCE: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE.
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Epilepsia , Acidente Vascular Cerebral , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Epilepsia/induzido quimicamente , Epilepsia/etiologia , Humanos , Itália , Pessoa de Meia-Idade , Pirrolidinonas/uso terapêutico , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do TratamentoRESUMO
Several studies reported acute symptomatic seizures as a possible neurological complication of COVID-19 pneumonia. Apart from metabolic imbalances, hypoxia, and fever, other ictogenic mechanisms are likely related to an immune-mediated damage. The same mechanisms are shared by other respiratory viruses. Since neurotropic properties of SARS-CoV-2 have been questioned, we investigated whether SARS-CoV-2 has a similar ictogenic potential to other respiratory non-neurotropic viruses. We conducted a retrospective study identifying 1141 patients with SARS-CoV-2 pneumonia and 146 patients with H1N1/H3N2 pneumonia. We found a similar prevalence of seizures in the two viral pneumonia (1.05% with SARS-CoV-2 vs 2.05% with influenza; pâ¯=â¯0.26). We detailed clinical, electroencephalographic, and neuroradiological features of each patient, together with the hypothesized pathogenesis of seizures. Previous epilepsy or pre-existing predisposing conditions (i.e., Alzheimer's disease, stroke, cerebral neoplasia) were found in one-third of patients that experienced seizures, while two-thirds of patients had seizures without known risk factors other than pneumonia in both groups. The prevalence of pre-existing predisposing conditions and disease severity indexes was similar in SARS-CoV-2 and H1N1/H3N2 pneumonia, thus excluding they could act as potential confounders. Considering all the patients with viral pneumonia together, previous epilepsy (pâ¯<â¯0.001) and the need for ventilatory support (pâ¯<â¯0.001), but not the presence of pre-existing predisposing conditions (pâ¯=â¯0.290), were associated with seizure risk. Our study showed that SARS-CoV-2 and influenza viruses share a similar ictogenic potential. In both these infections, seizures are rare but serious events, and can manifest without pre-existing predisposing conditions, in particular when pneumonia is severe, thus suggesting an interplay between disease severity and host response as a major mechanism of ictogenesis, rather than a virus-specific mechanism.
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COVID-19 , Vírus da Influenza A Subtipo H1N1 , Pneumonia Viral , Humanos , Vírus da Influenza A Subtipo H3N2 , Estudos Retrospectivos , SARS-CoV-2 , ConvulsõesRESUMO
In a recent study, we found that during 20.55⯱â¯1.60â¯h of artifact-free ambulatory EEG recordings, epileptiform discharges (EDs) longer than 2.68â¯s occurred exclusively in patients with Juvenile Myoclonic Epilepsy (JME) who experienced seizure recurrence within a year after the EEG. Here we expanded this analysis, exploring whether long EDs (>2.68â¯s), and short ones, were uniformly distributed during the day. Lastly, we evaluated the temporal distribution of seizure relapses. By Friedman test, we demonstrated that hourly frequencies of both short and long EDs were dependent on the hours of day and sleep-wake cycle factors, with an opposite trend. Short EDs were found mostly during the night (with two peaks at 1â¯AM and 6â¯AM), and sleep, dropping at the wake onset (pâ¯<â¯0.001). Conversely, long EDs surged at the wake onset (0.001), remaining frequent during the whole wake period, when compared to sleep (pâ¯=â¯0.002). Of note, this latter pattern mirrored that of seizures, which occurred exclusively during the wake period, and in 9 out of 13 cases at the wake onset. We therefore suggested that short and long EDs could reflect distinct pathophysiological phenomena. Extended wake EEG recordings, possibly including the awakening, could be extremely useful in clinical practice, as well as in further studies, with the ambitious goal of predicting seizure recurrences.
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Epilepsia Mioclônica Juvenil , Eletroencefalografia , Humanos , Convulsões , SonoRESUMO
OBJECTIVE: Markers of seizure recurrence are needed to personalize antiseizure medication (ASM) therapy. In the clinical practice, EEG features are considered to be related to the risk of seizure recurrence for genetic generalized epilepsies (GGE). However, to our knowledge, there are no studies analyzing systematically specific EEG features as indices of ASM efficacy in GGE. In this study, we aimed at identifying EEG indicators of ASM responsiveness in Juvenile Myoclonic Epilepsy (JME), which, among GGE, is characterized by specific electroclinical features. METHODS: We compared the features of prolonged ambulatory EEG (paEEG, 22 h of recording) of JME patients experiencing seizure recurrence within a year ("cases") after EEG recording, with those of patients with sustained seizure freedom for at least 1 year after EEG ("controls"). We included only EEG recordings of patients who had maintained the same ASM regimen (dosage and type) throughout the whole time period from the EEG recording up to the outcome events (which was seizure recurrence for the "cases", or 1-year seizure freedom for "controls"). As predictors, we evaluated the total number, frequency, mean and maximum duration of epileptiform discharges (EDs) and spike density (i.e. total EDs duration/artifact-free EEG duration) recorded during the paEEG. The same indexes were assessed also in standard EEG (stEEG), including activation methods. RESULTS: Both the maximum length and the mean duration of EDs recorded during paEEG significantly differed between cases and controls; when combined in a binary logistic regression model, the maximum length of EDs emerged as the only valid predictor. A cut-off of EDs duration of 2.68 seconds discriminated between cases and controls with a 100% specificity and a 93% sensitivity. The same indexes collected during stEEG lacked both specificity and sensitivity. SIGNIFICANCE: The occurrence of prolonged EDs in EEG recording might represent an indicator of antiepileptic drug failure in JME patients.
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Eletroencefalografia/métodos , Monitorização Ambulatorial/métodos , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Epilepsia Mioclônica Juvenil/fisiopatologia , Convulsões/fisiopatologia , Adulto , Anticonvulsivantes/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Monitorização Neurofisiológica/métodos , Recidiva , Convulsões/prevenção & controleRESUMO
BACKGROUND: SARS-CoV-2 infection is associated with a wide spectrum of neurological complications, including encephalitis. Most cases showed features consistent with a central nervous system (CNS) cytokine-mediated damage. However, few cases arguing for an autoimmune mechanism have been described, mainly as single reports or sparse in large case series involving other CNS manifestations. In this paper, we described a case of definite autoimmune limbic encephalitis (LE) COVID-19 related and reviewed the existing literature on other reported cases. CASE REPORT: Two weeks after the onset of COVID-19 infection, a 74-year-old woman presented with subacute confusion and focal motor seizures with impaired awareness, starting from left temporal region. Cerebrospinal fluid analysis revealed hyperproteinorrachia. Brain MRI showed bilateral T2/FLAIR hyperintensities in both hippocampi and total body PET/TC scan revealed hypermetabolism in basal ganglia bilaterally. A diagnosis of autoimmune LE was made. Thus, high dose corticosteroids and antiseizure medications were started, with a marked improvement of neurological conditions. LITERATURE REVIEW: We systematically reviewed the literature to identify all well-documented cases of definite autoimmune LE (according to Graus criteria) in patients with COVID-19 infection, identifying other five cases exhibiting a good response to immunomodulating therapy. CONCLUSION: A very limited number of autoimmune LE have been described until now. It is important to monitor neurological symptoms in COVID-19 patients and to consider the possibility of an autoimmune LE, in particular when altered mental status and seizures appear late in the disease course. This allows to promptly start the appropriate treatments and avoid unnecessary delays.
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BACKGROUND: Valproic acid (VPA) is the most effective medication in juvenile myoclonic epilepsy (JME) but, due to its teratogenic potential, levetiracetam (LEV) and lamotrigine (LTG) are preferred in women of childbearing age. The aim of this study was to compare the effectiveness and tolerability of LEV and LTG monotherapy in patients with a previous good seizure control in VPA monotherapy, in which VPA was withdrawn because of teratogenic potential or adverse drug effects. METHODS: We retrospectively analyzed 65 patients with JME which had been followedup at the Epilepsy Center of Pisa University Hospital, identifying 28 subjects who had been successfully treated with VPA monotherapy and who were shifted to another monotherapy. The second monotherapy was LEV for 14 subjects and LTG for the remaining 14 ones. Drug efficacy was measured in terms of seizure freedom for more than twelve months after reaching the minimum effective or the highest tolerated dose. RESULTS: In terms of seizure control, our analysis showed a significantly better outcome for LEV compared to LTG (14.3% and 71.4% of seizure relapse, respectively, pâ¯=â¯0.006) monotherapy. Such a higher efficacy was confirmed in those subjects with seizure relapse on LTG, who achieved good seizure control after switching to LEV monotherapy (89% of cases). Concerning tolerability, none of the patients reported severe side effects. CONCLUSION: Although obtained in a small case series, our analysis showed a significant better efficacy of LEV compared to LTG in monotherapy, in patients with JME with a good response to VPA, concerning both myoclonic and generalized tonic-clonic seizures.
Assuntos
Epilepsia Mioclônica Juvenil , Ácido Valproico , Anticonvulsivantes/uso terapêutico , Feminino , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Triazinas/uso terapêutico , Ácido Valproico/uso terapêuticoRESUMO
OBJECTIVE: Juvenile Myoclonic Epilepsy (JME) is a common genetic generalized epilepsy syndrome. Several studies have detailed cognitive and imaging abnormalities pointing to frontal lobe dysfunction, as well as disadvantageous behavioral traits and poor social outcome, challenging the commonly held view of JME being a benign disorder. Social cognition is the ability to elaborate mental representations of social interactions and to use them correctly in social contexts, and includes Theory of Mind (ToM), which pertains to the attribution of cognitive and affective mental states to self and others and seems to rely on complex fronto-temporal interactions. ToM has been recently assessed in focal epilepsy syndromes, but little is available for generalized epilepsies. We performed a cross-sectional study to assess social cognition, with an emphasis on ToM, as well as standard cognitive functions in patients with JME. METHOD: We recruited twenty JME patients and twenty matched controls. Tests used to assess social cognition and ToM included the Emotion Attribution Task, Strange Stories Task (SST), Faux Pas Task (FPT), Reading the Mind in the Eyes Task and Social Situation Task. Subjects were also assessed via an extensive neuropsychological battery. RESULTS: Patients exhibited worse performance in the SST and in several scores of the FPT. They also showed widespread cognitive impairment, involving executive functions, psychomotor speed, verbal and visuo-spatial memory. CONCLUSIONS: In addition to cognitive impairment for fronto-temporal tasks, some features of social cognition are also altered in JME. The latter deficit may underlie the poor social outcome previously described for these patients, and might also relate to imaging findings of frontal lobe dysfunction.