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This paper demonstrates a highly linear and efficient TETRA enhanced data service (TEDS) base-station RF power amplifier (RFPA). Based on the well-known combination of an envelope tracking (ET) power supply and a linear class-A/B RFPA, adequate adjacent channel power ratio (ACPR) and wide- band noise performance is shown to be enabled only by further incorporating high-bandwidth Cartesian feedback (CFB) and using a low-noise ET power supply. It is demonstrated that CFB loop bandwidth is limited by modulator/demodulator/RF path group delay to around 2 MHz in the considered setup, and that there exists a significant tradeoff between the depth of the ET and open-loop RFPA linearity, as well as overall efficiency. An empirical method for determining the permissible amount of switching ripple on the ET supply is presented, showing very good accuracy. Performance of the prototype RFPA system is verified experimentally with a 9.6-dB peak-to-average 50-kHz 16 quadrature amplitude modulation TEDS carrier, the setup providing 44-dBm (25 W) average RF output power at 400 MHz with 44% dc-to-RF efficiency state-of-the-art ACPR of less than -67 dBc, switching noise artifacts around -85 dBc, and an overall rms error vector magnitude below 4.5%. [ABSTRACT FROM AUTHOR]

Background: Pregnancy registries, designed to assess the safety of medications and vaccines for the exposed mother and fetus, have been developed since the 1990s. Malformations present in the exposed liveborn or stillborn infant or fetuses in elective terminations are the outcome of greatest concern. The experiences of the North American AED (antiepileptic drug) Pregnancy Registry (NAAPR) can be used to identify the challenges and limitations of a pregnancy registry in identifying congenital malformations., Methods: The NAAPR enrolls pregnant women who are taking one or more AEDs for any medical condition, but primarily to prevent seizures, and an unexposed comparison group. Participants are interviewed by clinical research coordinators (CRCs) at enrollment, later in pregnancy and postpartum. Malformations are identified in the mother's reports and her infant's medical records through age 12 weeks. A teratologist, blinded to exposure status, evaluates each potential malformation identified., Results: Among 10,982 pregnancies enrolled between 1997 and 2022, 282 malformations were identified in the 9677 AED-exposed and 15 among the 1305 unexposed infants. Isolated malformations, such as cleft palate, accounted for 84% of the malformations identified. Increased frequencies of oral clefts and myelomeningocele were associated with exposure to several different AEDs. Copies of reports from many diagnostic studies were not obtained and very few pregnancy losses had autopsies., Conclusions: The evaluation of the AED-exposed infants in a pregnancy registry is indirect. Improvements rely on the rapport established with the mothers by the CRCs and the mothers' willingness to assist in obtaining information from her infants' physicians., (© 2023 Wiley Periodicals LLC.)

Objective: To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery., Methods: This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log-binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs)., Results: The study population included infants born to 6,777 AED-WWE, 696 AED-WWOE, and 486 no-AED-WWOE. The risk of prematurity was 6.2% for no-AED-WWOE, 9.3% for AED-WWE (RR = 1.5, 95% CI = 1.0-2.1), and 10.5% for AED-WWOE (RR = 1.5, 95% CI = 1.0-2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no-AED-WWOE. The prevalence of SGA was 5.0% for no-AED-WWOE, 10.9% for AED-WWE (RR = 2.0, 95% CI = 1.3-3.0), and 11.0% for AED-WWOE (RR = 1.9, 95% CI = 1.2-2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate., Interpretation: Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457-465., (© 2017 American Neurological Association.)

Purpose: The International Lamotrigine Pregnancy Registry monitored for a signal of a substantial increase in the frequency of major congenital malformations associated with lamotrigine exposures in pregnancy over an 18-year period. Key methodological lessons are discussed., Methods: The strengths and weaknesses of the Registry were assessed using quantifiable methodological and operational parameters including enrollment, completeness of exposure and outcome data reporting, and lost to follow-up. The choice of comparator groups and stopping rules for registry closure were critically evaluated., Results: The reliance on voluntary reporting was associated with a clustered geographical distribution of registered pregnancies. The enrollment rate increased over time with new approvals and indications for lamotrigine and publication of interim data. Reporter burden was minimized through a streamlined data collection approach resulting in a high level of completeness of exposure and primary outcome data. Lost to follow-up rates were high (28.5% overall) representing a major limitation; incentives to increase the completeness of reporting failed to reduce rates. A lack of an internal comparator group complicated data interpretation; but external comparisons with multiple external groups allowed an assessment of consistency of outcome data across multiple data sources. A lack of a priori closure criteria prolonged the life of the Registry, and consideration of regulatory guidelines on this subject is encouraged at the time of conception of future registries., Conclusions: A successful pregnancy exposure registry requires ongoing flexibility and continuous re-assessment of enrollment, recruitment, and retention methods and the availability of comparison data, throughout its lifecycle., (Copyright © 2014 John Wiley & Sons, Ltd.)

Objective: To assess the possible effects of topiramate and zonisamide use during pregnancy on fetal growth., Methods: The study population was the singleton liveborns born to women who enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2012. Data were collected through telephone interviews at enrollment, 7 months of gestation, and postpartum. The prevalence of small for gestational age at birth among neonates exposed to topiramate and to zonisamide when either was used as monotherapy during pregnancy was compared with that among neonates exposed to lamotrigine monotherapy, a weight-neutral therapy, and the most common antiepileptic drug in the Registry. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated with multivariable log-binomial regression to control for potential confounders., Results: Data were available for 347 topiramate, 98 zonisamide, and 1,581 lamotrigine-exposed neonates. The mean gestational length was 39 weeks for all comparison groups. Prenatal exposure to topiramate or zonisamide was associated with a mean lower birth weight of 221 and 202 g, respectively, and a mean lesser neonatal length of 1 cm as compared with lamotrigine exposure (p<.01). The prevalence of small for gestational age was 6.8% for lamotrigine, 17.9% for topiramate (RR 2.4, 95% CI 1.8-3.3) and 12.2% for zonisamide (RR 1.6, 0.9-2.8). Similar results were found when a group of 457 unexposed neonates was used as the reference., Conclusions: Topiramate and zonisamide have been shown to reduce weight in adults. Our finding of a decrease in mean birth weight and length among neonates exposed in utero raises concern., Level of Evidence: II.

Antiepilepsy (AED) medications have revolutionized the treatment of epilepsy, transforming it from a chronic progressive disease with inevitable cognitive and motor decline to a disorder in which most effected persons operate largely in a normal fashion. As with all medications adverse experiences can occur. However, it has been clear that the alternative of uncontrolled seizures are more hazardous than pharmacological therapies. However, physicians are faced with a dilemma when treating fertile or pregnant women with epilepsy. Many AED impair the effectiveness of oral contraceptives. There is evidence that some AED may effect fertility. AED metabolism changes in pregnancy, making management of women with epilepsy more difficult. AED exposure in early pregnancy increases the risk of congenital malformations, and exposure during other phases may increase the risk of developmental delay and neonatal hemorrhage. AED can be secreted in breast milk, thus extending the exposure into infancy. The exclusion of women of childbearing age from clinical trials limits our ability to collect information on the pharmacokinetics and potential adverse experiences of AED in pregnancy. Thus, when new medications are marketed, clinicians and their patients have no information on how to best manage conception, pregnancy, and lactation. This article discusses these issues in detail and describes our current understanding of the use of AED in women of childbearing age.

Women with epilepsy present health care providers with unique problems and opportunities for advancement of care. The fundamentals of epileptic pathophysiology are similar in both sexes. There are, however, some significant differences. Cosmetic effects of antiepileptic drugs (AEDs) may have different implications for women. Women who have seizures associated with their menstrual cycle may need special attention regarding their cyclic hormonal changes and AED selection. Antiepileptic drugs may reduce the effectiveness of hormonal contraception. Women with epilepsy have higher rates of infertility and an increased prevalence of reproductive and endocrine disorders. The majority of women with epilepsy have normal, healthy children, but their pregnancies are considered high risk due to an increase in seizure frequency, metabolic alterations of AEDs (which complicate management), and an increased risk of adverse pregnancy outcomes. These issues and an approach to optimize the management of women with epilepsy are discussed.

In the United States, approximately 1.1 million women of childbearing age have epilepsy. Even though antiepileptic drugs (AEDs) control the seizures of about 80% of patients with epilepsy, the management of women with epilepsy (WWE) presents physicians with unique problems, ranging from the cosmetic consequences of some AEDs (e.g., changes in weight) to the seizures of catamenial epilepsy (apparently related to a relative lack of progesterone during the luteal phase of the menstrual cycle). In addition, the effectiveness of hormonal contraceptives can be reduced by enzyme-inducing AEDs. The pregnancies of WWE present a greater risk for complications: one-quarter to one-third of WWE experience an increase in seizure frequency. In addition, difficulties during labor and adverse outcomes (e.g., fetal mortality and malformations, neonatal hemorrhage, low birth weight, and developmental delay) are more likely. The practitioner must choose a course that both prevents seizures and minimizes fetal exposure to AEDs.

We report on a new familial neurodegenerative disease with associated dementia that has presented clinically in the fifth decade, in both genders, and in each of several generations of a large family from New York State-a pattern of inheritance consistent with an autosomal dominant mode of transmission. A key pathological finding is the presence of neuronal inclusion bodies distributed throughout the gray matter of the cerebral cortex and in certain subcortical nuclei. These inclusions are distinct from any described previously and henceforth are identified as Collins bodies. The Collins bodies can be isolated by simple biochemical procedures and have a surprisingly simple composition; neuroserpin (a serine protease inhibitor) is their predominant component. An affinity-purified antibody against neuroserpin specifically labels the Collins bodies, confirming their chemical composition. Therefore, we propose a new disease entity-familial encephalopathy with neuroserpin inclusion bodies (FENIB). The conclusion that FENIB is a previously unrecognized neurodegenerative disease is supported by finding Collins bodies in a small kindred from Oregon with familial dementia who are unrelated to the New York family. The autosomal dominant inheritance strongly suggests that FENIB is caused by mutations in the neuroserpin gene, resulting in intracellular accumulation of the mutant protein.

Aberrant protein processing with tissue deposition is associated with many common neurodegenerative disorders; however, the complex interplay of genetic and environmental factors has made it difficult to decipher the sequence of events linking protein aggregation with clinical disease. Substantial progress has been made toward understanding the pathophysiology of prototypical conformational diseases and protein polymerization in the superfamily of serine proteinase inhibitors (serpins). Here we describe a new disease, familial encephalopathy with neuroserpin inclusion bodies, characterized clinically as an autosomal dominantly inherited dementia, histologically by unique neuronal inclusion bodies and biochemically by polymers of the neuron-specific serpin, neuroserpin. We report the cosegregation of point mutations in the neuroserpin gene (PI12) with the disease in two families. The significance of one mutation, S49P, is evident from its homology to a previously described serpin mutations, whereas that of the other, S52R, is predicted by modelling of the serpin template. Our findings provide a molecular mechanism for a familial dementia and imply that inhibitors of protein polymerization may be effective therapies for this disorder and perhaps for other more common neurodegenerative diseases.

Purpose: To describe a potential association between male infertility and valproate (VPA) exposure. VPA has been implicated in the development of polycystic ovarian disease and subsequent menstrual and infertility problems in women with epilepsy. Infertility has been well described in population-based studies of persons with epilepsy. The low marital rates for men with epilepsy have previously been thought to play a major contributing role., Methods: We report a case of a 32-year-old man whose wife and he were able to bear a child before the development of his epilepsy. With VPA monotherapy, the family were unable to conceive despite 4 years of unprotected intercourse. An infertility evaluation of the man revealed a very low sperm count of < 50,000/ml, no motile sperm, < 10% viability, and 100% with abnormal structure. Follicle-stimulating hormone, luteinizing hormone, and testosterone levels were normal., Results: Felbamate (FBM) was initiated and VPA discontinued for improved seizure control. Within 4 months, the couple conceived their second child. A seminal analysis revealed a sperm count of > 16 million, 50% motility, 78% viability, and 72% with abnormal structure., Conclusions: One must be cautious in extrapolating from a case report, but these findings strongly suggest a direct effect of VPA on spermatic structure and function.

Treatment of epilepsy extends far beyond the administration and monitoring of antiepileptic drug therapy. Persons with epilepsy have cognitive, vocational, and psychosocial needs that may exceed the scope of the primary care physician's clinical responsibilities. In such cases, the physician can assemble and manage a team of medical and social service professionals to address these needs. By establishing this support system and maintaining effective communication with the patient and the management team, the primary care physician offers patients with epilepsy the opportunity to improve and maintain their quality of life and receive safe and effective pharmacologic treatment.

Despite all of our advances women with epilepsy face obstacles when it comes to pregnancy and childbearing. Many of these obstacles are social, based on incorrect and inappropriate attitudes of the public towards persons with epilepsy. Unfortunately many of the uninformed public are health care providers. We must continue to educate not only our patients but our colleagues so that women with epilepsy will cease to face discriminatory behaviour. Most women with epilepsy can conceive and bear healthy children. They have higher probabilities of infertility but this is often amenable to treatment. Complications of pregnancy are higher and revolve primarily around the increased risk of maternal seizures. Careful monitoring of the clinical condition of the patient and her free anticonvulsant levels will obviate much of this difficulty. Maternal seizures themselves can pose hazards for women with epilepsy and their offspring and generalized convulsive seizures are clearly to be avoided. Adverse pregnancy outcomes tend to be seen more often in particular: congenital malformations 4-6%; dysmorphic features < 10%; neonatal haemorrhage < 7%; fetal death and neonatal and infant mortality a two to threefold increase over the general population; and an uncertain risk of developmental delay particularly in the area of language acquisition. Of the potential variables of interest: anticonvulsants, maternal seizures during gestation, and the genetics of maternal epilepsy, it is at present unclear which is the most important in determining a good pregnancy outcome. Current research suggests that anticonvulsant drugs are probably responsible for the increased risk of malformations. Malformations are, however, only one of the adverse outcomes of concern. Risks can be reduced by ensuring good seizure control; monotherapy: preconceptual use of multivitamins with folate. The plethora of new anticonvulsants offers us new opportunities for improving the function and control of persons with epilepsy. Unfortunately we are uncertain how hazardous the newer anticonvulsant drugs are in pregnancy. Felbamate, gabapentin, lamotrigine, vigabatrine, and topiramate have all been recently introduced. The number of exposed women is so small that no pattern or estimates of risk can be determined at this time. Careful monitoring as is being performed by the Lamotrigine and North American Epilepsy and Pregnancy Registries will hopefully provide the necessary safety information in the near future. All of the risks aside, the majority of women with epilepsy can and will have healthy children.

Women with epilepsy who are of childbearing age need to understand what the risks of pregnancy are. These women have a 33% risk of increased seizures, a twofold increase in risk of hemorrhage, eclampsia, premature labor, and an increased need for cesarean sections. Babies born to women with epilepsy face a higher risk of miscarriage, stillbirth, prematurity, developmental delay, and major malformations. Seizure control should be obtained without clinical toxicity. Monotherapy reduces the risk of adverse outcomes.

Conventional wisdom and prevailing medical practice strongly support the belief that medication should be avoided during pregnancy. For the nearly one million women of childbearing age with epilepsy in the United States this is often difficult, if not impossible, and for many of these women becoming pregnant raises many conflicting issues. Women with epilepsy may face a possible increase in the frequency and severity of seizures, and in generalized tonic-clonic seizures there is a small but increased risk of miscarriage.

Clinicians and their women patients with epilepsy face difficult decisions. There is evidence to suggest that antiepileptic drugs increase the risk of major malformations, minor anomalies, neonatal hemorrhage, and delayed fetal growth and development. Maternal seizures also appear to be disadvantageous to the fetus, increasing the risk of miscarriage, premature labor, intracranial hemorrhage, and perhaps, developmental or learning difficulties. Both medications and seizures have the potential to cause difficulties. This article discusses change in antiepileptic drug metabolism, changes in seizure frequency, adverse pregnancy outcomes, and principles of management.

Women were enrolled in our prospective cohort study of epilepsy and pregnancy to determine the developmental outcome of offspring and the immediate outcome of pregnancy. Women with epilepsy (case group) were enrolled before conception or during the first trimester, and women without epilepsy or chronic illness (control group) were recruited during pregnancy. We have now completed 12-month evaluation for 43 children in the case group and 41 in the control group. We found no difference in growth parameters between the groups. The children in the case group had a higher mean number of minor anomalies than did those in the control group, and their features were consistent with those previously reported for children exposed to AEDs in utero. Developmental differences between the two groups varied, with some differences reaching statistical significance. The findings reported here are preliminary, since the children will be evaluated through 3 years of age.