Lamotrigine vs levetiracetam in female patients of childbearing age with juvenile absence epilepsy: A Bayesian reanalysis.

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.

Topiramate ban in women of childbearing potential with idiopathic generalized epilepsy: Does effectiveness offset the teratogenic risks?

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.

Adjunctive brivaracetam and sustained seizure frequency reduction in very active focal epilepsy.

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.

Pre-existing frontal lobe dysfunction signs as predictors of subsequent neurotoxicity in CAR T cell therapy: insights from a case series.

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.

A case of intravascular large B cell lymphoma with brain involvement mimicking progressive multifocal leukoencephalopathy.

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.

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures.

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.

Ictogenesis of viral pneumonia: A comparison between SARS-CoV-2 and H1N1/H3N2.

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; p = 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 (p < 0.001) and the need for ventilatory support (p < 0.001), but not the presence of pre-existing predisposing conditions (p = 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.

Prolonged epileptic discharges predict seizure recurrence in JME: Insights from prolonged ambulatory EEG.

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.

Response to levetiracetam or lamotrigine in subjects with Juvenile Myoclonic Epilepsy previously treated with valproic acid: A single center retrospective study.

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, p = 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.

Prolonged and short epileptiform discharges have an opposite relationship with the sleep-wake cycle in patients with JME: Implications for EEG recording protocols.

In a recent study, we found that during 20.55 ±â€¯1.60 h of artifact-free ambulatory EEG recordings, epileptiform discharges (EDs) longer than 2.68 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 (>2.68 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 1 AM and 6 AM), and sleep, dropping at the wake onset (p < 0.001). Conversely, long EDs surged at the wake onset (0.001), remaining frequent during the whole wake period, when compared to sleep (p = 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.

An educational campaign about epilepsy among Italian primary school teachers. 2. The results of a focused training program.

A cohort of 582 Italian primary school teachers underwent a questionnaire survey to test their knowledge and attitudes toward epilepsy and verify whether an intensive and focused educational program could result in improvement of knowledge and attitudes. The program consisted of a presentation of the clinical manifestations of epilepsy and the distribution of informative brochures and an educational kit on the disease and its management to be used with their students. After several months, 317 teachers were retested using the same questions. Upon retest, the number of "don't know" answers decreased significantly for almost all questions. This was not the case for negative attitudes. The same holds true for teachers believing that epilepsy is a source of learning disability and social disadvantage. These findings support the beliefs that education on epilepsy is more likely to affect ignorance than prejudice and that stronger interventions are needed to counteract stigmatizing behaviors.

Novel MTCYB mutation in a young patient with recurrent stroke-like episodes and status epilepticus.

The acronym "MELAS" (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) denotes patients with histological, biochemical and/or molecular evidence of mitochondrial disease who experience stroke-like episodes. Here we report on a girl with repeated stroke-like episodes and status epilepticus, who was diagnosed with MELAS due to a novel mitochondrial cytochrome b gene (MTCYB) mutation (m.15092G>A, which predicts p.G116S). Western blotting and in silico analyses suggested that this mutation could affect the stability of complex III. Cytochrome b is the only mtDNA-encoded subunit of respiratory chain complex III. Mutations in MTCYB have been associated with isolated mitochondrial myopathy and exercise intolerance, and rarely with multisystem and/or central nervous system involvement. If the m.3243A>G and other common MELAS mutations are absent in several tissues, MTCYB should be sequenced from muscle in patients with stroke-like episodes, especially if muscle histology does not support a mitochondrial myopathy and lactic acidosis is absent.

Predictors of Seizure Recurrence in Women With Idiopathic Generalized Epilepsy Who Switch From Valproate to Another Medication.

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.

Daytime sleepiness in de novo untreated patients with epilepsy.

The aims of our study were to evaluate excessive daytime sleepiness in a group of de novo untreated people with epilepsy using a comprehensive and standardized approach, including subjective evaluation and neurophysiological and performance tests, and to compare these results with those obtained in a control group. Forty-seven patients with epilepsy (17 affected by primary generalized epilepsy and 30 by partial epilepsy), with a new epilepsy diagnosis and never treated, and 44 controls underwent Multiple Sleep Latency Test (preceded by nocturnal polysomnography), simple/complex visual reaction times, and Epworth Sleepiness Scale evaluation. Newly diagnosed and drug-free patients with epilepsy did not differ from controls in any of the tests performed to evaluate daytime sleepiness. In clinical practice, daytime sleepiness is a well-known and frequent complaint of patients with epilepsy, but different mechanisms and causes, such as associated psychiatric or sleep disorders, nocturnal seizures, sleep fragmentation, and antiepileptic drugs, must be taken into account. Excessive daytime sleepiness should not be considered an unavoidable consequence of epilepsy. Thus, a complete diagnostic work-up in patients with epilepsy and sleepiness should be undertaken whenever possible.

3-T magnetic resonance angiography in primary angiitis of the central nervous system.

OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a rare disease characterized by an inflammatory process of intracranial vessels. Magnetic resonance angiography (MRA) (3 T) offers increased signal-to-noise ratio and background suppression, leading to better depiction of the intracranial vessels. The aim of our work was to compare the sensitivity of 3-T MRA to that of 1.5-T MRA in the diagnosis of PACNS. METHODS: Eight patients with PACNS and signs of angiitis at digital subtraction angiography (DSA) underwent MRA at 1.5 and 3 T. Magnetic resonance angiograms obtained with time-of-flight (TOF) technique were evaluated for the presence of stenosis with respect to DSA. RESULTS: In PACNS patients, DSA identified 827 intracranial stenoses. Sensitivity for vessel stenosis of 3-T TOF MRA was 47% and 14% for 1.5-T TOF. CONCLUSIONS: Time-of-flight MRA at 3 T improved the sensitivity of MRA in the noninvasive preliminary evaluation of patients with PACNS.

Ictal EEG modifications in temporal lobe epilepsy.

Temporal lobe epilepsy is the most common type of epilepsy in adults with medically intractable, localisation-related epilepsy, amenable to surgery. Together with clinical and neuroimaging data, presurgical ictal scalp-EEG findings are often sufficient to define the epileptogenic zone. It is widely believed that ictal scalp-EEG findings in temporal lobe epilepsy are represented by 5-9-Hz lateralised rhythmic theta activity or 2-5-Hz lateralised rhythmic delta activity. On the basis of experimental models and experience with intra-cerebral EEG recordings, the pattern of low-voltage fast activity is considered to be the electrophysiological hallmark of the epileptogenic zone. We reviewed the ictal scalp-EEG data relating to 111 seizures in 47 patients with temporal lobe epilepsy who underwent video-EEG recordings during presurgical work-up. We found that 35 patients (74.4%) showed flattening, low-voltage fast activity or fast activity as the initial EEG pattern. When visible, the rhythmic delta or theta activity followed the fast activity. Low-voltage fast activity, flattening or fast activity occurs in the majority of patients with temporal lobe epilepsy and represents the main ictal EEG pattern. Low-voltage fast activity (or similar) is also identifiable as the initial ictal EEG pattern in scalp-EEG recordings.

Alzheimer's Disease and Neurosyphilis: Meaningful Commonalities and Differences of Clinical Phenotype and Pathophysiological Biomarkers.

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.

Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy.

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.

Distinct limbic connectivity in left and right benign mesial temporal lobe epilepsy: Evidence from a resting state functional MRI study.

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.