Perinatal outcome in anti-NMDAr encephalitis during pregnancy-a systematic review with individual patients' data analysis.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDAr) antibody encephalitis is an autoimmune disorder characterized by synaptic NMDAr current disruption and receptor hypofunction, often affecting women during pregnancy. Clinical manifestations associated with anti-NMDAr encephalitis can occur both in the mother and fetus. METHODS: We generated a systematic search of the literature to identify epidemiological, clinical, and serological data related to pregnant women with anti-NMDAr encephalitis and their children, analyzing the fetal outcomes. We examined the age and neurologic symptoms of the mothers, the presence of an underlying tumor, immunotherapies used during pregnancy, duration of the pregnancy, and type of delivery. RESULTS: Data from 41 patients were extrapolated from the included studies. Spontaneous interruption of pregnancy, premature birth, and cesarean section were reported in pregnant women with NMDAr encephalitis. Several fetal and neonatal symptoms (e.g., movement disorders, spina bifida, poor sucking, respiratory distress, cardiac arrhythmias, infections, icterus, hypoglycemia, and low birth weight) depending on the mother's serum anti-NR1 concentration were also reported. CONCLUSIONS: We characterized the outcomes of children born from mothers with anti-NMDAr encephalitis, analyzing the pivotal risk factors related to pregnancy and maternal disorder. Neuropsychiatric involvement seems strictly related to pathogenic NMDAr antibodies detected in maternal and/or neonatal serum. These findings clarify a complex condition to manage, outlining the risks associated with pregnant women with anti-NMDAr encephalitis and also providing a concrete guide for therapeutic strategies to prevent potential harm to the fetus and the child's neurodevelopment.

A systematic review of immunotherapy in high-grade glioma: learning from the past to shape future perspectives.

High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years, immunotherapy has changed the prognosis of many cancers, increasing the hope for HGG therapy. We conducted a comprehensive search on PubMed, Scopus, Embase, and Web of Science databases to include relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Fifty-two papers were finally included (44 phase II and eight phase III clinical trials) and further divided into four different subgroups: 14 peptide vaccine trials, 15 dendritic cell vaccination (DCV) trials, six immune checkpoint inhibitor (ICI) trials, and 17 miscellaneous group trials that included both "active" and "passive" immunotherapies. In the last decade, immunotherapy created great hope to increase the survival of patients affected by HGGs; however, it has yielded mostly dismal results in the setting of phase III clinical trials. An in-depth analysis of these clinical results provides clues about common patterns that have led to failures at the clinical level and helps shape the perspective for the next generation of immunotherapies in neuro-oncology.

Heart rate variability modification as a predictive factor of sudden unexpected death in epilepsy: How far are we? A systematic review and meta-analysis.

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected death in people with epilepsy, with or without evidence of an epileptic seizure. The pathophysiological mechanism underlying SUDEP appears to be partly associated with an autonomic nervous system (ANS) dysfunction. Heart rate variability (HRV) analysis is a reliable, non-invasive method for detecting fluctuations in the ANS. In this systematic review we analyzed the data available in the literature on changes in HRV parameters in patients with SUDEP. METHODS: We carried out a systematic search of the literature to identify the quantitative variations of HRV in epileptic patients with SUDEP. The following databases were used: Pubmed, Google Scholar, EMBASE, and CrossRef. A pooled analysis was carried out, and the results obtained were compared using mean difference (MD). The review was registered on the PROSPERO platform (CRD42021291586). RESULTS: Seven articles were included, with a total of 72 SUDEP cases associated with altered HRV parameters. Generally, a reduction of SDNN (standard deviation of the RR intervals) and RMSSD (root mean square differences of successive RR intervals) was reported in most SUDEP patients. According to MD, the SUDEP patients showed no differences in time and frequency domain parameters compared to controls. However, a trend toward increased low frequency and high frequency ratio (LF/HF) was observed in the SUDEP patients. CONCLUSIONS: HRV analysis is a valuable method for assessing cardiovascular risk and cardioautonomic impairment. Although a possible association between HRV variation and SUDEP has been reported, further studies are needed to assess the potential role of HRV modifications as a SUDEP biomarker.

Treatment of benzodiazepine-refractory status epilepticus: A retrospective, cohort study.

INTRODUCTION: Status epilepticus (SE) is a frequent neurological emergency, derived from the failure of mechanisms responsible for seizure termination. The present study aims to compare the efficacy of the most common antiseizure medications (ASMs) employed for the treatment of benzodiazepine-refractory SE. METHODS: We performed a retrospective cohort study of all SE episodes treated in our hospital between January 2016 and December 2020. Inclusion criteria were: age ≥ 18 years; a diagnosis of status epilepticus. Exclusion criteria were: status epilepticus resolved by initial therapy with benzodiazepines; impossibility to retrieve medical records. We considered as effective the ASM that was the last drug introduced or increased in dose before termination of SE and without changes in the co-medication. RESULTS: A total of 244 episodes in 219 patients were included in the study. The mean age of the final study cohort was 63.6 ± 19.2, with 108 (49%) men. In the total cohort, phenytoin (PHT) showed the highest response rate (57.6%), followed by lacosamide (LCM) (40.7%) and valproate (VPA) (39.8%). The comparative efficacy among the different drugs was significantly different (p < 0.001). In the pairwise comparisons, VPA was superior to levetiracetam (LEV) (response rate: 39.75% vs 24.71%; p = 0.004), but not to LCM. Phenytoin had a significantly higher resolution rate compared to VPA (response rate: 57.63% vs 39.75%; p = 0.02) and LEV (response rate: 57.63% vs 24.71; p < 0.001). The clinical predictors of anaesthetics administration were a disorder of consciousness upon clinical presentation, previous diagnosis of epilepsy, and younger age. CONCLUSION: In our cohort of SE, PHT showed higher effectiveness in terminating established SE, as well as refractory SE in the subgroup of patients treated with anaesthetics.

Non convulsive refractory status epilepticus induced by thiocolchicoside (TCC) intrathecal injection: A case report.

TCC is a semisynthetic molecule widely used in clinical settings as a pain killer and myorelaxant. Several neurological side effects have been reported in association with TCC treatment including somnolence, confusion and seizure, the latter in a lower percentage of patients. Some previous reports described seizure onset after TCC intake in adulthood. However, major epileptological complication, namely status epilepticus, has never been previously reported in association with TCC treatment. In our report, we describe a case of acute refractory non-convulsive status epilepticus (NCSE) in the context of a TCC-induced acute toxic encephalopathy (ATE) in a woman without any previous neurological or physical comorbidities.

Heart rate variability is reduced during the menstrual phase in women with catamenial C1-type temporal lobe epilepsy.

INTRODUCTION: Temporal lobe epilepsy (TLE) is the most frequent focal epilepsy in adulthood. Catamenial C1-type TLE, is characterized by a cyclic seizure exacerbation during the menstrual phase. The heart rate variability (HRV) analysis assesses cardiac autonomic control and may represent a biomarker for Sudden Unexpected Death in Epilepsy (SUDEP). It is plausible that female sex hormones can influence HRV. These changes might be more pronounced in patients suffering from catamenial C1-type TLE where hormonal changes also increase seizure susceptibility. To that aim, we evaluated HRV changes during the menstrual phase of women suffering from catamenial C1-type TLE. METHODS: We enrolled 12 adults with a diagnosis of catamenial C1-type TLE (Catamenial Group) and 12 age-, and seizure-frequency-matched controls with TLE (Non-Catamenial Group). Each patient underwent a 20-minute EEG + EKG recording in resting state during the menstrual phase. HRV parameters were calculated with a short-lasting analysis of EKG records. Time domain-related, frequency domain-related, as well as non-linear analysis parameters, were compared between the two groups. RESULT: Compared to the Non-Catamenial Group, the Catamenial Group showed significant reductions in SDNN (p-value = 0.01), RMSSD (p-value = 0.04), pNN50 (p-value = 0.001), LnLF ms2 (p-value = 0.05), LnHF ms2 (p-value = 0.007), SD1 (p-value = 0.02), and SD2 (p-value = 0.01). These results were independent from age, disease duration, numbers of ASM, and seizure etiology. CONCLUSION: Our data provide experimental evidence that vagal output is reduced during the menstrual phase in patients with catamenial C1-type TLE. These results indicate that, during the menstrual phase, patients with catamenial C1-type TLE may be at a higher risk of developing cardiac dysfunctions and SUDEP.

Status migrainosus: a potential adverse reaction to Comirnaty (BNT162b2, BioNtech/Pfizer) COVID-19 vaccine-a case report.

BACKGROUND: Coronavirus disease-19 (COVID-19) due to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the largest emergency that humanity had to be dealing with in the last century. During the last months, different types of vaccines have been designed to contain the ongoing SARS-CoV-2 pandemic, with successful results in many countries. Comirnaty (Pfizer/BioNtech) COVID-19 vaccine is a lipid nanoparticle-formulated, nucleoside mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2. Although vaccines have an undeniable efficacy, they can also present several neurological side effects, including headache. According to ICHD-3 Classification, status migrainosus (SMg) is described as a debilitating migraine attack lasting for more than 72 h. Symptoms of SMg can be very severe, preventing the normal daily activities of the individual. CASE PRESENTATION: In the present report, we describe a case of SMg that lasted 11 days, time correlated with the second dose of COVID-19 vaccine (Pfizer/Comirnaty) in a 37-year-old woman with a history of migraine without aura. CONCLUSIONS: In patients with a history of migraine, COVID-19 vaccination could lead to a worsening of headache and, in rare cases, to the development of a SMg. This may be related to the inflammatory response that occurs after vaccination.

Impact of COVID-19 vaccine on epilepsy in adult subjects: an Italian multicentric experience.

OBJECTIVES: To investigate the safety and tolerability of COVID-19 vaccines in people with epilepsy (PwE). METHODS: In this multicentric observational cohort study, we recruited adult patients (age > 18 years old) with epilepsy who attended the Outpatient Epilepsy Clinic from 1st July to 30th October 2021. We administered to the patients a structured questionnaire and interview on demographic and epilepsy characteristics, current treatment, previous SARS-CoV-2 infection, vaccine characteristics, post-vaccine seizure relapse, other side effect, variation of sleep habits, caffeine, or alcohol intake. Seizure frequency worsening was defined as a ratio between mean monthly frequency post-vaccination and mean monthly frequency pre-vaccination superior to 1. Patients were categorized in two groups: patients with seizure frequency worsening (WORSE) and patients with seizure stability (STABLE). RESULTS: A total of 358 people participated with a mean age of 47.46 ± 19.04. Focal seizure (79.1%), generalized epilepsy (20.4%), and unknown types of epilepsy (0.5%) were detected among participants. In total, 31 (8.7%) people expressed that they were not willing to receive a COVID-19 vaccine; 302 patients (92.35%) did not experience an increase in the seizure frequency (STABLE-group) whereas 25 patients (7.65%) had a seizure worsening (WORSE-group). Post-vaccine seizures occurred mainly in the 7 days following the administration of the vaccine. Patients in the WORSE-group were treated with a mean higher number of anti-seizure medication (ASMs) (p = 0.003) and had a higher pre-vaccine seizure frequency (p = 0.009) compared with patients in the STABLE-group. Drug-resistant epilepsy was also associated with seizure worsening (p = 0.01). One-year pre-vaccination seizure frequency pattern demonstrated that patients in the WORSE-group had a higher frequency pattern (p < 0.001). Multivariate analysis of the vaccinated group showed that only the seizure frequency pattern (confidence interval [CI] = 1.257-2.028; p < 0.001) was significantly associated with seizure worsening. CONCLUSION: In our cohort of vaccinated PwE, only a little percentage had a transient short-term increase of seizure frequency. The present study demonstrates that COVID-19 vaccines have a good safety and tolerability profile in the short term in PwE.

Cerebral venous thrombosis without thrombocytopenia after a single dose of COVID-19 (Ad26.COV2.S) vaccine injection: a case report.

BACKGROUND: The coronavirus pandemic became the hard challenge for the modern global health system. To date, vaccination is the best strategy against Sars-Cov-2-related illness. About 3 billions of people received at least one of the approved vaccines. The related adverse events were reported during the various experimental phases, but newer and less common side effects are emerging post-marketing. Vaccine-induced thrombocytopenia with thrombosis (VITT) is one of these insidious adverse reactions and it is considered responsible of venous thrombosis, in both the splanchnic and the cerebral circulation. Although its mechanism has been presumably established, resembling that observed in heparin-induced thrombocytopenia, some venous thromboses seem not to recognize this etiology and their pathogenesis remains unknown. Here we described a case of cerebral venous thrombosis after administration of the Ad26.COV2.S, presenting without thrombocytopenia, paving the way for possible novel causes of this vaccine-induced pathological condition. CASE PRESENTATION: A 45-year-old woman came to our observation for bilateral periorbital headache associated with retro-orbital pain started 8 days after administration of COVID vaccine Jannsen. Ophthalmologic exam showing a bilateral papilledema raised the suspicion of intracranial hypertension. Cerebral magnetic resonance imaging revealed signal alteration with T1-positive contrast enhancement in the right temporal and insular lobes suggestive of cerebral venous thrombosis. The absence of thrombocytopenia and platelet factor 4 (PF-4) antibodies led the clinicians to rule out VITT. The patient was treated successfully with warfarin. CONCLUSION: Venous thrombosis occurring after COVID-19 vaccination represents an adverse event of special interest. Patients with thrombosis and thrombocytopenia appear to be affected by a general thrombophilic state, sustained by an autoimmune mechanism, and show a higher mortality. Thrombosis without thrombocytopenia's pathogenesis has not yet been clarified, but laboratory data and good response to vitamin K antagonists help clinicians in the differential diagnosis with VITT. Future research will allow us to discover other possible mechanisms and maybe identify a subgroup of patients with a higher risk of developing this medical complication.

Migraine Pharmacological Treatment and Cognitive Impairment: Risks and Benefits.

Migraine is a common neurological disorder impairing the quality of life of patients. The condition requires, as an acute or prophylactic line of intervention, the frequent use of drugs acting on the central nervous system (CNS). The long-term impact of these medications on cognition and neurodegeneration has never been consistently assessed. The paper reviews pharmacological migraine treatments and discusses their biological and clinical effects on the CNS. The different anti-migraine drugs show distinct profiles concerning neurodegeneration and the risk of cognitive deficits. These features should be carefully evaluated when prescribing a pharmacological treatment as many migraineurs are of scholar or working age and their performances may be affected by drug misuse. Thus, a reconsideration of therapy guidelines is warranted. Furthermore, since conflicting results have emerged in the relationship between migraine and dementia, future studies must consider present and past pharmacological regimens as potential confounding factors.

Perampanel may represent an effective treatment for the prevention of migraine comorbid with epilepsy.

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.

New daily persistent headache after SARS-CoV-2 infection: a report of two cases.

BACKGROUND: The 2019 Coronavirus (SARS-CoV-2) is a novel respiratory virus which causes Coronavirus Disease19 (COVID-19). Although the predominant clinical picture of COVID-19 is represented by respiratory symptoms, neurological manifestations are being increasingly recognized. Headache, in particular migraine-like and tension types, has been largely reported in patients suffering from COVID-19 both in the acute and the healing phase of the infection. New daily persistent headache (NDPH) is a primary headache characterized by persistent and daily painful symptoms, with pain becoming continuous and non-remitting within 24 h, and lasting more than 3 months. Even though an increasing number of reports describe patients who develop a persistent headache, diagnosis of NPDH has been rarely explored in the context of COVID-19. METHODS: Two patients with persistent headache and Sars-CoV-2 infection were identified. Both underwent a full clinical and neuroradiological evaluation. Blood sample with inflammatory biomarkers search was also performed. RESULTS: According to International Classifications of Headache Disorders diagnosis of probable new daily persistent headache was made. The treatment with high doses of steroids was associated with relief of symptoms. CONCLUSIONS: Our report described two cases of probable NDPH due to SARS-CoV-2 infection. Clinical evaluation of COVID-19 patients presenting with persistent headache should take into consideration NDPH. Given the supposed major role for neuroinflammation in the genesis of Sars-CoV-2-driven NDPH, immunomodulatory therapy should be promptly started. In line with this hypothesis, we obtained a good therapeutic response to short-term high dose of corticosteroids.

Case Report: Brain tumor's pitfalls: two cases of high-grade brain tumors mimicking autoimmune encephalitis with positive onconeuronal antibodies.

Background: Glioblastoma (GBM) is the most common primary brain tumor in adulthood. Initial diagnosis is generally based on clinical and MRI findings, which may be misinterpreted as other neurological pictures, including autoimmune encephalitis (AE). AE is a heterogeneous group of neuroinflammatory diseases due to the presence of auto-antibodies targeting antigens on neuronal synaptic or cell surface. In the present report, we describe two peculiar cases of GBM initially misdiagnosed as AE, focusing on the diagnostic pitfalls and the treatment strategies. Methods: We report the case of two patients with high-grade brain tumors, initially misdiagnosed and treated for AE. Clinical, laboratory, and neuroradiological data are discussed in terms of differential diagnosis between AE and GBM. Results: The presence of atypical brain MRI findings and the unresponsiveness to immunosuppressive treatment are major red flags in the differential diagnosis between AE and GBM. In these cases, a brain biopsy is necessary to confirm the diagnosis. Conclusions: Atypical brain tumor presentation causes a diagnostic and therapeutic delay. A positive onconeural autoantibodies result should always be interpreted cautiously, considering the possibility of a false-positive test. A brain biopsy is mandatory for a definite diagnosis.

Diagnosis and treatment of late-onset myoclonic epilepsy in Down syndrome (LOMEDS): A systematic review with individual patients' data analysis.

INTRODUCTION: The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS. METHODS: We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748). RESULTS: Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control. CONCLUSIONS: AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option.

Heart rate variability modifications in adult patients with early versus late-onset temporal lobe epilepsy: A comparative observational study.

OBJECTIVES: Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsy. TLE is associated with cardio-autonomic dysfunction and increased cardiovascular (CV) risk in patients over the fifth decade of age. In these subjects, TLE can be classified as early-onset (EOTLE; i.e., patients who had developed epilepsy in their youth) and late-onset (LOTLE; i.e., patients who developed epilepsy in adulthood). Heart rate variability (HRV) analysis is useful for assessing cardio-autonomic function and identifying patients with increased CV risk. This study compared changes in HRV occurring in patients over the age of 50, with EOTLE or LOTLE. METHODS: We enrolled twenty-seven adults with LOTLE and 23 with EOTLE. Each patient underwent a EEG and EKG recording during 20-minutes of resting state and a 5-minutes hyperventilation (HV). Short-term HRV analysis was performed both in time and frequency domains. Linear Mixed Models (LMM) were used to analyze HRV parameters according to the condition (baseline and HV) and group (LOTLE and EOTLE groups). RESULTS: Compared to the LOTLE group, the EOTLE group showed significantly decreased LnRMSSD (natural logarithm of the root mean square of the difference between contiguous RR intervals) (p-value=0.05), LnHF ms2 (natural logarithm of high frequency absolute power) (p-value=0.05), HF n.u. (high frequency power expressed in normalized units) (p-value=0.008) and HF% (high frequency power expressed in percentage) (p-value=0.01). In addition, EOTLE patients exhibited increased LF n.u. (low frequency power expressed in normalized units) (p-value=0.008) and LF/HF (low frequency/high frequency) ratio (p-value=0.007). During HV, the LOTLE group exhibited a multiplicative effect for the interaction between group and condition with increased LF n.u. (p = 0.003) and LF% (low frequency expressed in percentage) (p = 0.05) values. CONCLUSIONS: EOTLE is associated with reduced vagal tone compared to LOTLE. Patients with EOTLE may have a higher risk of developing cardiac dysfunction or cardiac arrhythmia than LOTLE patients.

Autoimmune encephalitis during pregnancy: A diagnostic and therapeutic challenge-A systematic review with individual patients' analysis and clinical recommendations.

Several reports have described the autoimmune encephalitis' (AE) possible onset during pregnancy. In this systematic review, we summarize the available data on the diagnostic and therapeutic approach to AE during pregnancy, highlighting the associated maternal and fetal clinical outcomes. A systematic search of the literature was performed. The following databases were used: PubMed, Google Scholar, EMBASE, and CrossRef. The revision was registered on the PROSPERO platform (CRD42022336357). Forty-nine patients were included. AE onset was mainly observed during the first and the second trimester of pregnancy with psychiatric manifestations and seizures as main onset symptoms. CSF analysis showed AE-specific autoantibody positivity in 33 patients (anti-NMDA receptor as the most frequent). EEG generally showed normal findings. MRI revealed pathological findings in less than half of patients. Tumor screening was positive in 14 cases. First-line immunotherapy (single or combined) was generally employed while second line was administered in a minority of patients. Levetiracetam was the most used antiseizure medication. Cesarean section was performed in 18 women. Most of the women had an excellent early outcome after delivery but 22 showed persistent neurological deficits in long-term follow-up. Fetal outcome was positive in 33 cases, whereas 12 cases of fetal death were reported. A logistic regression showed that no variable significantly influenced the odds of good/bad maternal and fetal clinical outcome. Diagnosis and treatment of AE during pregnancy is challenging. The rate of miscarriage in women with AE seems to be higher than the general population. In addition, mothers may show long-term neurological deficits.

Anti N-methyl-D-aspartate receptor (NMDAr) encephalitis during pregnancy: A case report.

Anti-N-methyl-D-aspartate receptor (NMDAr) antibody encephalitis is an autoimmune disorder characterized by reduced synaptic activity of the NMDAr due to circulating antibodies that target the NR1 subunit. Few cases of anti-NMDAR encephalitis during pregnancy have been described. The permeation of anti-NR1 antibodies through the placenta can be instrumental in the development of complications in newborns. We describe a case of a young woman suffering from anti-NMDAR encephalitis during the first trimester of pregnancy and focus on diagnostic and therapeutic management.

Perampanel enhances the cardiovagal tone and heart rate variability (HRV) in patients with drug-resistant temporal lobe epilepsy.

OBJECTIVE: The temporal lobe plays a central role in the regulation of the "Central Autonomic Network" and cardiovascular functions. The blockade of glutamatergic pathways in the temporal lobe affects cardio-autonomic control. Perampanel (PER) is a non-competitive agonist of the AMPA receptor. This study evaluated PER effects on cardiac autonomic control in patients affected by drug-resistant TLE (DRTLE). METHODS: We enrolled 40 adults with DRTLE treated with PER as add-on therapy (PER group) and 32 DRTLE age, sex, and seizure-frequency matched controls treated with different additional anti-seizure medication (ASM) as add-on therapy (No-PER group). HRV analysis was performed on 5-minute EKG recording in resting state before and 6-months after the introduction of add-on ASM. Linear Mixed Models (LMM) were used to analyzed HRV variables according to time (baseline and 6-months follow-up) and groups. RESULTS: At baseline no differences were detected between PER group and No-PER group according to time-domain and frequency-domain HRV parameters. At the follow-up, in PER group a multiplicative effect for the interaction between treatment and time was observed for MeanRR (ms) (p=0.03), LnRMSSD (ms) (p=0.04), LnHF (ms2) (p<0.001), HF n.u. (p=0.001), HF% (p=0.002) with increased values, and for LnLF (ms2) (p=0.001), LF n.u. (p=0.001), LF% (p=0.01), and LF/HF (p<0.001) with reduced values. The change in seizure frequency after add-on therapy was comparable between the two groups (p=0.81) CONCLUSIONS: Our data support the notion that PER increases the vagal tone in DRTLE. This activity may exert a cardioprotective effect by reducing the risk of developing cardiac arrhythmias. Furthermore, given the correlations between HRV modifications and the occurrence of SUDEP, future studies will need to test the protective effects of PER on SUDEP.