Levetiracetam, lamotrigine and carbamazepine: which monotherapy during pregnancy?

OBJECTIVE: Epilepsy treatment during pregnancy is still challenging. The study is aimed at comparing the efficacy and safety of carbamazepine (CBZ), lamotrigine (LTG) and levetiracetam (LEV) monotherapies during pregnancy in women with focal (FE) or generalized (GE) epilepsy. METHODS: A multicentre retrospective study was conducted to evaluate seizures frequency and seizure freedom (SF) rate during 3 months before pregnancy, each trimester of gestation and post-partum period in women on monotherapy with CBZ, LTG and LEV. RESULTS: Fifty-seven pregnancies (45 FE, 12 GE) on monotherapy (29 CBZ, 11 LTG, 17 LEV) were included. A significant reduction of seizure frequency was found in the first trimester of pregnancy as compared with that one before pregnancy (p = 0.004), more evident in GE (p = 0.003) and in LEV group (p = 0.004). The SF rate significantly increased in the first trimester in comparison to that one before pregnancy and persisted in the post-partum period in the whole sample (p < 0.001) and in women on LEV (p = 0.004). Besides, 88.57% of SF women before pregnancy remained unchanged during gestation and the post-partum period. One major heart malformation in CBZ and no major malformations in LTG and LEV groups were found. CONCLUSIONS: A better clinical outcome during pregnancy emerged since the first trimester in comparison to the before-pregnancy period, mostly evident in women with GE and LEV therapy, reinforcing the hypothesis of a protective role of pregnancy versus seizures. SF before pregnancy represents a significant predictive factor of good clinical outcome during gestation and the post-partum period. Compared to CBZ, LTG and LEV showed a better safety profile.

Development of high-efficiency molecular adsorbent recirculating system: preliminary report.

Molecular Adsorbent Recirculating System (MARS) is a liver support system widely employed in the treatment of liver failure. The method is normally well tolerated. To develop a liver support system combining high efficiency and tolerability, we modified the MARS albumin circuit with the insertion of double adsorption units in parallel. Four patients have been treated with this modified method (high-efficiency MARS, HE MARS): two had very high serum bilirubin and two had very high total bile acids. After a single MARS session bilirubin was reduced more with HE MARS than standard MARS (from 27.6 to 52.3% in patient A and from 27.9 to 49.1% in patient B), and bile acid reduction increased from 40 to 59.8% in patient C and from 39.9 to 60% in patient D. The results of this preliminary investigation in only a very small number of patients do support the possibility of developing a liver support system that combines good tolerability and high efficacy.

Effectiveness of Highly Purified Cannabidiol in Refractory and Super-Refractory Status Epilepticus: A Case Series.

INTRODUCTION: Refractory and super-refractory status epilepticus are medical emergencies that must be promptly treated in consideration of their high mortality and morbidity rate. Nevertheless, the available evidence of effective treatment of these conditions is scarce. Among novel antiseizure medications (ASMs), highly purified cannabidiol (hpCBD) has shown noteworthy efficacy in reducing seizures in Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). CASE PRESENTATION: Here, we present two cases of effective use of hpCBD in both refractory and super- refractory status epilepticus. The administration of the nasogastric tube permitted the resolution of status epilepticus without adverse events. At 6-month follow-up, both patients were on hpCBD treatment, which continued to be efficacious for treating seizures. CONCLUSION: According to our experience, hpCBD should be taken into consideration as an add-on therapy of RSE and SRSE while also considering the possibility of maintaining this treatment during the follow-up of patients. However, more studies and real-world experiences are needed to better understand its effectiveness in this setting and the interaction with other ASMs.

Fiber-optic trap-on-a-chip platform for probing low refractive index contrast biomaterials.

Dual-beam fiber trapping is a versatile technique for manipulating microparticles. We fabricate and evaluate the performance of a compact trap-on-a-chip design and demonstrate, for what we believe is the first time, trapping of low-contrast (m<1.005) lipid vesicles in solution. Counterpropagating fibers are fixed along the chip channel, and we calibrate the trap by optically displacing polystyrene microspheres from the trap center. Measured scattering forces are ~30-49 pN from each beam. Stable trapping and reversible deformation of lipid vesicles is demonstrated under femtonewton trapping forces. This chip has applications in probing a variety of soft biomaterials, such as biological cells, lipid membranes, and protein assemblies.

Acceptability of Switching to Long-Acting Cabotegravir and Rilpivirine Among People Living with HIV on Dolutegravir/Rilpivirine Combination: A Single-Center Experience.

The availability of long-acting cabotegravir and rilpivirine injection combination requires some changes in service delivery of outpatient HIV clinics; it is therefore important for clinicians to know the potential number of people living with HIV (PLWH) who are interested in a long-acting antiretroviral treatment. We aimed to determine in an outpatient clinic the number of PLWH, on dolutegravir/rilpivirine, accepting a switch to an injectable long-acting antiretroviral treatment, and the reasons underlying this choice. In our single-center study, in this subset of HIV-infected patients, the main cause for refusal of a long-acting injectable regimen was the need for the administration to be done in hospital, as required in Italy, suggesting that current regulations about this aspect must be changed.

Sleep architecture in drug-naïve adult patients with epilepsy: Comparison between focal and generalized epilepsy.

OBJECTIVE: Sleep impairment is one of the most common comorbidities affecting people with epilepsy (PWE). The bidirectional relation between epilepsy and sleep has been widely established. Several studies investigated subjective sleep quality and daytime vigilance in PWE, highlighting frequent complaints of sleep fragmentation, difficulties in falling asleep, and daytime sleepiness. The present study aimed to evaluate sleep structure in drug-naive PWE, distributed on the basis of epilepsy type, and compared with controls. METHODS: This observational study included adult patients newly diagnosed with epilepsy and drug-naive as well as a control group of healthy subjects. All PWE and controls underwent a dynamic 24-h EEG with signals for sleep recording to evaluate sleep architecture, structure, continuity, and fragmentation. RESULTS: Twenty-four PWE were included and distributed in two groups based on epilepsy type. Eleven patients were included in the generalized epilepsy group (63.6% male; 34.91 ± 9.80 years) and 13 patients in the focal epilepsy group (53.8% male; 38.69 ± 12.74 years). The control group included 16 subjects (56.3% male; 32.75 ± 12.19 years). Patients with generalized or focal epilepsy had a significantly lower sleep efficiency than controls. Moreover, both patient groups presented the alteration of markers of sleep fragmentation and loss of continuity, with higher indices of sleep stage transitions and arousal. Finally, the two patient groups presented less REM sleep than controls. SIGNIFICANCE: This study highlighted the alteration of sleep quality, continuity, and stability in both patients with focal or generalized epilepsy compared with controls, also in the absence of ictal events. This sleep impairment resulted in the reduction of REM sleep. Therefore, these findings may be explained by the increase in awakenings and sleep stage shifts, which may be attributed to both sleep networks impairment and neurotransmission dysfunction in PWE, and also possibly triggered by paroxysmal interictal abnormalities.

Periodic sharp wave complexes identify a distinctive phenotype in Creutzfeldt-Jacob disease.

OBJECTIVE: The aim of our study was to evaluate the diagnostic and prognostic value of Electroencephalogram (EEG), brain Magnetic Resonance Imaging (MRI) and cerebrospinal fluid features, currently representing Creutzfeldt-Jacob Disease (CJD) diagnostic criteria. METHODS: A retrospective study on rapidly progressive dementia patients admitted at the Neurology Clinic of the University of Rome "Tor Vergata" between 2015 and 2020 was conducted. We evaluated clinical, EEG, cerebrospinal fluid and neuroradiological findings. RESULTS: Our analysis included 13 patients with probable CJD and 18 patients with non-CJD rapidly progressive dementia. Periodic sharp wave complexes were observed in 7/13 CJD and in 4/18 non-CJD patients (p =.151). The sub-analysis according to the EEG features revealed that CJD patients with earlier periodic sharp wave complexes had a significantly lower average survival time (p =.003), a shorter time to admission (p =.003) and lower levels of cerebrospinal fluid p-tau (p =.008) compared to CJD patients without periodic sharp wave complexes. Finally, they did not show signs of signal alteration on Fluid Attenuated Inversion Recovery images. CONCLUSIONS: Despite the lowest diagnostic specificity and sensibility among the CJD criteria, periodic sharp wave complexes could identify a distinctive phenotype hallmarked by a faster evolution, a reduced survival time and specific MRI and cerebrospinal fluid features. SIGNIFICANCE: The early presence of the typical EEG pattern may play a prognostic role in CJD.

Clinical Impact of Monoclonal Antibodies in the Treatment of High-Risk Patients with SARS-CoV-2 Breakthrough Infections: The ORCHESTRA Prospective Cohort Study.

The clinical impact of anti-spike monoclonal antibodies (mAb) in Coronavirus Disease 2019 (COVID-19) breakthrough infections is unclear. We present the results of an observational prospective cohort study assessing and comparing COVID-19 progression in high-risk outpatients receiving mAb according to primary or breakthrough infection. Clinical, serological and virological predictors associated with 28-day COVID-19-related hospitalization were identified using multivariate logistic regression and summarized with odds ratio (aOR) and 95% confidence interval (CI). A total of 847 COVID-19 outpatients were included: 414 with primary and 433 with breakthrough infection. Hospitalization was observed in 42/414 (10.1%) patients with primary and 8/433 (1.8%) patients with breakthrough infection (p < 0.001). aOR for hospitalization was significantly lower for breakthrough infection (aOR 0.12, 95%CI: 0.05-0.27, p < 0.001) and higher for immunocompromised status (aOR:2.35, 95%CI:1.08-5.08, p = 0.003), advanced age (aOR:1.06, 95%CI: 1.03-1.08, p < 0.001), and male gender (aOR:1.97, 95%CI: 1.04-3.73, p = 0.037). Among the breakthrough infection group, the median SARS-CoV-2 anti-spike IgGs was lower (p < 0.001) in immunocompromised and elderly patients >75 years compared with that in the immunocompetent patients. Our findings suggest that, among mAb patients, those with breakthrough infection have significantly lower hospitalization risk compared with patients with primary infection. Prognostic algorithms combining clinical and immune-virological characteristics are needed to ensure appropriate and up-to-date clinical protocols targeting high-risk categories.

LDL apheresis: a novel technique (LIPOCOLLECT 200).

Therapeutic means to lower Lp(a) are limited. The most effective method to reduce plasma Lp(a) concentration significantly is therapeutic apheresis, namely, low-density lipoprotein (LDL) lipoprotein(a) (Lp(a)) apheresis. A novel technique based on reusable LDL adsorber called Lipocollect 200 (Medicollect, Rimbach, Germany) allows the removal of both LDL and Lp(a) from plasma. Two male patients with hyperLp(a)lipoproteinemia and angiographically established progressive coronary heart disease, without rough elevation of LDL-cholesterol, who did not respond to diet and medication were submitted to 50 LDL Lp(a) aphereses with Lipocollect 200 LDL Lp(a)-adsorber at weekly and biweekly intervals. Total cholesterol and LDL cholesterol plasma levels fell significantly by 48.3% (+/-6.7) to 61.6% (+/-12.7) (first patient), and 42.5% (+/-6.3) to 60.6% (+/-14.3) (second patient), respectively (all differences: P < or = 0.001). High-density lipoprotein (HDL)-cholesterol concentration in plasma did not show statistically significant change. Plasma triglycerides were also significantly reduced by 43.6% (+/-24.4) (first patient) and 42.3% (+/-13) (second patient) (both differences: P < or = 0.001). Plasma Lp(a) showed a statistically significant percent reduction in plasma as expected: 64.7 +/- 9.5 (first patient), and 59.1 +/- 6.7 (second patient) (both differences: P < or = 0.001). Plasma fibrinogen concentration was decreased by 35.9% (+/-18.7) (P < or = 0.05) (first patient) and 41.8% (+/-11.5) (second patient) (P < or = 0.005). Considering the reduction rate between the first and the last procedures, we have compared the mean percent reduction of the first five treatments (from session #1 to #5) with the last five treatments (from session #21 to #25). We have observed an increasing reduction of all activity parameters on both patients apart from HDL-cholesterol (first patient) and triglyceride (second patient) that showed a decreasing reduction rate. Both patients followed the prescribed schedule and completed the study. Clinically, all sessions were well tolerated and undesired reactions were not reported. The Lipocollect 200 adsorber proved to have a good biocompatibility. In this study, the adsorber reusability for several sessions was confirmed.