EEG extreme delta brush: An ictal pattern in patients with anti-NMDA receptor encephalitis.

INTRODUCTION: The anti-NMDA receptor (NMDAr) encephalitis-associated syndrome includes neuropsychiatric symptoms, impaired consciousness, seizures, autonomic instability, and hypoventilation. The electroencephalographic (EEG) activity throughout the course of the disease has still not been well documented. We reviewed electroclinical data of patients with NMDAr encephalitis to characterize their EEG and its clinical correlation. MATERIAL AND METHODS: We retrospectively identified 16 patients with NMDAr encephalitis from 8 Spanish medical centers, 15 of whom underwent video-EEG in the acute phase. RESULTS: In 15 patients (11 females, median age: 37.4, range: 14-87 years), seizures occurred in 9 (60%) and status epilepticus (SE) in 5 (33.3%). Magnetic resonance imaging (MRI) was abnormal in 10 (66.6%), and CSF (cerebrospinal fluid) was normal in 3 and abnormal in 12, with positive PCR (polymerase chain reaction) for Mycoplasma pneumoniae (1/15) and herpes simple virus (1/15). An ovarian teratoma was found in 1 patient and other malignancies (small cell lung carcinoma) in 1 patient. The EEG was abnormal in the acute phase in 14/15 (93.3%). Extreme delta brush (EDB) was observed in 5 (33.3%), and the presence of EDB was associated with SE in all cases. Rhythmic delta activity without EDB was observed in 5 (33.3%), while excessive beta activity was present in 4 (26.6%). Extreme delta brush can follow a pattern of well-characterized electroclinical seizures. CONCLUSIONS: Almost invariably, patients with NMDAr encephalitis had abnormal EEG. The presence of EDB, which can follow a pattern of well-characterized electroclinical seizures, in our patients was associated with seizures and SE. These findings suggest that EDB could be an evolutive pattern of an SE in NMDAr encephalitis. This article is part of a Special Issue entitled "Status Epilepticus".

Low-dose sodium valproate in the treatment of idiopathic generalized epilepsies.

OBJECTIVE: Most patients with idiopathic generalized epilepsies (IGEs) have good seizure control when on antiepileptic drugs. To analyze prospectively the response to low-dose sodium valproate (VPA) treatment (<1000 mg/day) together with plasma VPA levels in a cohort of patients with IGE. METHODS: Patients with IGE were selected and followed for almost 2 years. In patients on VPA with no seizures in the last year, VPA dose was lowered to <1000 mg/day. Newly diagnosed patients with IGE started treatment on VPA directly on this low dose. RESULTS: Fifty-four patients were included, with juvenile myoclonic epilepsy (JME) in 23 (42.6%), juvenile absence epilepsy (JAE) in 17 (31.5%), and generalized tonic-clonic seizures only (GTCS only) in 14 (25.9%). VPA at low dose was administered to 38 (70%) patients. Mean plasma VPA level was 44.21 mg/l (18-78; SD 15.18). Seizure relapse during the 2-year follow-up was observed in 8 (21%). A reduction in adverse events was observed (P < 0.048). The only factor related to efficacy of VPA at low dose was syndromic diagnosis. Low-dose VPA controlled 92.9% (13) of patients with GTCS only, 78.3% (18) of those with JME, and 29.5% (5) of those with JAE. CONCLUSIONS: Low-dose VPA was a highly effective treatment for the majority of those with JME and GTCS only. The seizures in JAE tended to be more resistant to treatment, usually requiring higher doses of VPA or polytherapy.

Gender bias in the diagnosis of cardiovascular disorders in Catalonia.

In this study, we examine patient gender bias on the probabilities of both visiting the cardiologist and of being diagnosed with a heart disease. Using data from the Catalan Health Survey, we are able to conclude that there is gender bias both in access and diagnosis for patients with high likelihood of suffering heart issues. Our findings suggest that women have lower probabilities of visiting the cardiologist and of being diagnosed with a heart disease after controlling for risk factor and demographics characteristics.

Abnormal sudomotor skin responses to temperature and pain stimuli in syringomyelia.

Thermoalgesic sensory deficits in patients with syringomyelia may escape objective documentation with conventional electrophysiological techniques. We examined six patients with radiologically proven centrospinal cavities and patchy thermoalgesic sensory deficits by recording the evoked potentials and the sympathetic sudomotor skin responses (SSR) to laser stimuli. While electrical stimuli to the affected areas induced evoked potentials and SSRs of normal latency and amplitude, CO2 laser stimulation induced absent or abnormally reduced evoked potentials. Also, warmth and heat pain stimulation with a Peltier thermode induced absent or abnormal SSRs when applied over the affected areas but well defined SSRs when applied to the corresponding contralateral areas. Our results reveal the utility of recording the SSR to pain and temperature stimuli over specific body sites to demonstrate impairment of pain and temperature pathways in patients with syringomyelia. Comparison of electrical versus laser and temperature induced SSRs is an objective means to evaluate the selective thermoalgesic sensory deficit in these patients.

Quantitative Thermal Testing Profiles as a Predictor of Treatment Response to Topical Capsaicin in Patients with Localized Neuropathic Pain.

There are no reliable predictors of response to treatment with capsaicin. Given that capsaicin application causes heat sensation, differences in quantitative thermal testing (QTT) profiles may predict treatment response. The aim of this study was to determine whether different QTT profiles could predict treatment outcomes in patients with localized peripheral neuropathic pain (PeLNP). We obtained from medical records QTT results and treatment outcomes of 55 patients treated between 2010 and 2013. Warm sensation threshold (WST) and heat pain threshold (HPT) values were assessed at baseline at the treatment site and in the asymptomatic, contralateral area. Responders were defined as those who achieved a > 30% decrease in pain lasting > 30 days. Two distinct groups were identified based on differences in QTT profiles. Most patients (27/31; 87.1%) with a homogenous profile were nonresponders. By contrast, more than half of the patients (13/24, 54.2%) with a nonhomogenous profile were responders (p = 0.0028). A nonhomogenous QTT profile appears to be predictive of response to capsaicin. We hypothesize patients with a partial loss of cutaneous nerve fibers or receptors are more likely to respond. By contrast, when severe nerve damage or normal cutaneous sensations are present, the pain is likely due to central sensitization and thus not responsive to capsaicin. Prospective studies with larger patient samples are needed to confirm this hypothesis.

Assessment of costs and benefits of management of gestational diabetes mellitus.

The purpose of this pilot study was to perform a cost-identification analysis of care for gestational diabetes mellitus (GDM) by determining the direct costs of the diagnostic procedures and treatment used for the outpatient management of GDM (program input costs) and the direct costs of maternal hospitalization after diagnosis of GDM, delivery of the baby, and newborn care (outcome costs). Reimbursed average charges in the Northern California (NoCal) managed care market in 1996 were used to establish the direct costs, and the direct costs were then applied to the elements of care and pregnancy outcomes of three GDM management programs in NoCal, Southern California (SoCal), and New England (NewEng), using prospectively collected data. Reimbursed amounts for the detailed elements of GDM management (program input costs) are presented in the categories of diagnosis of GDM, diabetes treatment supplies, doctor's office visits, office visits to ancillary providers, and fetal surveillance. Program input costs per patient were $817 for diet-treated and $1,838 for insulin-treated women in NoCal, and were estimated to be $882 for diet-treated and $1,425 for insulin-treated women in NewEng. Program input costs for women requiring insulin treatment who were randomized to premeal or postprandial blood glucose testing (N Engl J Med 333:1237, 1995) in SoCal were estimated to be $3,596 per patient for the premeal group and $3,770 per patient for the postprandial group. Reimbursed amounts for health care expenditures related to pregnancy outcomes are detailed in the categories of hospital and physician charges for maternal antepartum hospitalization ($1,864 for 2 days), vaginal delivery with 50% use of epidural anesthesia ($4,050), cesarean section ($5,932), and neonatal intensive care ($9,130 for 4 days). Outcome costs per patient were $5,792 for diet-treated and $6,462 for insulin-treated women in NoCal. Outcome costs per patient were estimated to be $6,096 for diet-treated and $11,216 for insulin-treated women in NewEng, and $8,013 for the premeal blood glucose group and $7,495 for the postprandial blood glucose group in SoCal (both groups required insulin treatment). Incremental cost-effectiveness of postprandial monitoring in the SoCal controlled trial was $35 per patient in input costs per cesarean section averted and $25 per patient in input costs per neonatal intensive care unit day prevented. The benefit-to-cost ratio of the difference in input and outcome costs was 2.98 in favor of postprandial monitoring in the SoCal study. Cost analysis should be included in clinical trials of the management of GDM.

Chronological supplement to the Carcinogenic Potency Database: standardized results of animal bioassays published through December 1982.

This paper is a chronological supplement to our earlier publication, "A Carcinogenic Potency Database of the Standardized Results of Animal Bioassays." We report here results of carcinogenesis bioassays published in Technical Reports of the National Cancer Institute/National Toxicology Program between July 1980 and December 1982, and the general literature between July 1981 and December 1982. This supplement includes results of 280 long-term, chronic experiments of 114 test compounds, and reports the same information about each experiment in the same plot format as the earlier paper: e.g., the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 and its statistical significance, dose response, author's opinion about carcinogenicity, and literature reference. While a number of appendices are provided to facilitate use of this supplement, we have not duplicated here the material published earlier. Instead, we refer the reader to the earlier publications (Peto et al. and Gold et al.) for a thorough description of the numerical index of carcinogenic potency (TD50), a guide to the plot of the database, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. For 44 of the 114 chemicals reported in this second plot, results of earlier experiments are also given in the first plot; since only 1981-1982 results are reported here, the first plot is required for these repeated compounds. In this paper we also give corrections for errors that appeared in the earlier publication.

A carcinogenic potency database of the standardized results of animal bioassays.

The preceding paper described our numerical index of carcinogenic potency, the TD50 and the statistical procedures adopted for estimating it from experimental data. This paper presents the Carcinogenic Potency Database, which includes results of about 3000 long-term, chronic experiments of 770 test compounds. Part II is a discussion of the sources of our data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. Part III is a guide to the plot of results presented in Part IV. A number of appendices are provided to facilitate use of the database. The plot includes information about chronic cancer tests in mammals, such as dose and other aspects of experimental protocol, histopathology and tumor incidence, TD50 and its statistical significance, dose response, author's opinion and literature reference. The plot readily permits comparisons of carcinogenic potency and many other aspects of cancer tests; it also provides quantitative information about negative tests. The range of carcinogenic potency is over 10 million-fold.

The effects of carbohydrate restriction in patients with diet-controlled gestational diabetes.

OBJECTIVE: To determine the effect of carbohydrate restriction on perinatal outcome in patients with diet-controlled gestational diabetes mellitus (GDM). METHODS: Women with diet-controlled GDM were divided non-randomly into two groups based on their dietary carbohydrate content: those with low dietary carbohydrate content (below 42%) and those with high dietary carbohydrate content (exceeding 45%). Subjects kept dietary accounts and were followed with daily fasting and postprandial glucose assessments. Subjects also were tested daily for urinary ketones. Glycosylated hemoglobin, mean fasting and postprandial glucose values, incidence of macrosomia and large for gestational age (LGA) infants, cesarean deliveries for cephalopelvic disproportion and macrosomia, and need for insulin therapy were compared between the groups. RESULTS: The two groups were identical in terms of demographic characteristics. Significant reductions in the postprandial glucose values were seen among subjects in the low-carbohydrate group (P < .04). Fewer subjects in the low-carbohydrate group required the addition of insulin for glucose control (P < .047; relative risk [RR] 0.14; 95% confidence interval [CI] 0.02, 1.00). The incidence of LGA infants was significantly lower in the low-carbohydrate group (P < .035; RR 0.22; 95% CI 0.05, 0.91). Subjects in the low carbohydrate group also had a lower rate of cesarean deliveries for cephalopelvic disproportion and macrosomia (P < .037; RR 0.15; 95% CI 0.04, 0.94). CONCLUSION: Carbohydrate restriction in patients with diet-controlled GDM results in improved glycemic control, less need for insulin therapy, a decrease in the incidence LGA infants, and a decrease in cesarean deliveries for cephalopelvic disproportion and macrosomia.

Term early-onset neonatal seizures: obstetric characteristics, etiologic classifications, and perinatal care.

OBJECTIVE: To describe obstetric characteristics and etiologic classifications and assess perinatal care in term neonates with early-onset seizures. METHODS: We performed a retrospective review of neonatal and obstetric records of neonates delivered at term with a diagnosis of early-onset seizures between January 1981 and December 1992 at Long Beach Memorial Medical Center. Data regarding obstetric characteristics and etiologic classifications of the seizures were abstracted from the medical records. Lack of antepartum testing in high-risk patients, delayed intervention with nonreassuring antepartum or intrapartum fetal heart rate patterns, birth trauma, and failure to use prophylactic antibiotics or treat infection were the criteria used for identifying seizures that were potentially preventable. RESULTS: Forty term neonates had early-onset seizures out of 60,712 live births (0.07%). These seizures were attributed to hypoxic events in 15 neonates (37.5%), cerebral malformations in seven (17.5%), cerebral infarcts in seven (17.5%), intracranial hemorrhage in five (12.5%), infection in three, and an unknown etiology in three. Twenty-three neonates had 5-minute Apgar scores of 7 or greater (cerebral malformations excluded). Seven of these neonates (30%) had cerebral infarcts. A review of all records identified nine cases (22.5%) of the early-onset seizures as potentially preventable. CONCLUSION: The majority of the term early-onset neonatal seizures identified did not appear to be preventable. Many of the neonates with 5-minute Apgar scores of 7 or greater had cerebral infarcts.

Prepulse inhibition of the blink reflex by laser stimuli in normal humans.

The subcortical integrative effects of laser-induced activation of pain ascending tracts were examined in 11 healthy volunteers, aged 22-52 years. Subjects underwent either CO2 laser stimulation at the dorsum of the hand, electrical stimulation of digital nerves at the 3rd finger, or mechanical taps to the first dorsal interosseous space, preceding a blink reflex elicited by a supraorbital nerve electrical stimulus. The percentage inhibition induced in the R2 response of the blink reflex was similar for the three different stimulus modalities, but occurred at a different time interval. Compared to control trials, the R2 response of the test trials was a mean of 23.1% at the interval of 250 ms with laser stimuli, 17.4% at the interval of 100 ms with electrical stimuli to the 3rd finger, and 20.6% at the interval of 90 ms with a mechanical tap to the 1st interosseous space. Activation of pain receptors induces prepulse inhibition of the blink reflex at a delay corresponding to a slowly conducting pathway. The percentage inhibition is similar to that observed with other somatosensory inputs.

Labor and delivery management of the multiple gestation.

Labor and delivery management of multiple gestations remains controversial. The authors review issues relating to the management of labor and the administration of anesthesia in twin gestations. A comprehensive review of published data pertaining to delivery route planning for twins using fetal presentation, gestational age, and estimated fetal weight is presented. Individualization of intrapartum care in twin gestations is imperative.

Cervical assessment: visual or digital?

Our hypothesis for this study was that visual cervical assessment is not equivalent to digital assessment in patients with uterine contractions. We compared visual with digital cervical examinations done on 133 gravid women evaluated in the labor and delivery department because of uterine contractions. Patients at 27 weeks' gestation or more, subjectively in early labor, were prospectively entered into the study. Cervical dilatation and effacement were determined by two separate examiners blinded to each other's assessment, one by digital examination and the other by visual examination, in random order no more than 5 minutes apart. Eight of 133 patients were excluded from data analysis because of inability to visualize the cervix during speculum examination. Data analysis was done with correlation coefficient and the Bland and Altman test for agreement of two clinical measurements. Visual examination only underestimated actual cervical dilation by 0.60 cm (95% confidence interval [CI] 0.58 to 0.62 cm) and the limits of agreement were -2.06 cm (95% CI -2.02 to -2.09 cm) to 3.25 cm (95% CI 3.21 to 3.29 cm). Similarly, visual assessment underestimated effacement by 14.2% (95% CI 13.7% to 14.6%) and the limits of agreement were -41.3% (95% CI -40.5% to 42.0%) to 69.9% (95% CI 68.8% to 70.4%). In conclusion, cervical assessment in patients with uterine contractions who are thought to be in labor by visual speculum examination is not equivalent to that by digital examination. This difference seems to only be clinically significant if the cervix is more than 3 cm dilated.

The effects of umbilical cord milking in extremely preterm infants: a randomized controlled trial.

OBJECTIVE: Delayed cord clamping has been shown to decrease the need for transfusion in preterm neonates, but may delay resuscitation. The aim of this study was to determine whether umbilical cord milking compared with immediate cord clamping in extremely preterm deliveries reduces the need for neonatal red blood cell transfusion. STUDY DESIGN: Women admitted to a tertiary care center and expected to deliver between 24 to 28 completed weeks of gestation were randomized to cord milking before clamping or immediate cord clamping. The primary outcome was the risk of neonatal transfusion, reported as risk ratio (RR) and 95% confidence interval (CI). RESULT: Of 113 women who were enrolled and randomized, 56 were assigned to cord milking with 36 remaining eligible and completing the study and 57 were assigned to the control group with 39 remaining eligible and completing the study. Albeit not statistically significant, neonates in the cord milking group were less likely to require transfusion compared with those in the control group (RR: 0.86; 95% CI: 0.73 to 1.0). Neonates whose cords were milked had higher hematocrits at birth (P=0.004) and were less likely to develop an intraventricular hemorrhage (P=0.0195). CONCLUSION: Milking the umbilical cord of a preterm neonate is an easy intervention with the potential to improve perinatal outcomes. Our results suggest that milking of the cord increases the neonate's initial hematocrit and may lessen the need for transfusion in the neonatal period. The observed reduction in the incidence of intraventricular hemorrhage may have important long-term implications that warrant further study.

Prediction of an abnormal karyotype in fetuses with omphalocele.

The aim of this study was to assess the value of ultrasonographic evaluation in predicting abnormal karyotypes in fetuses with omphalocele. Forty fetuses with antenatally diagnosed omphalocele and available karyotype results were reviewed. Ultrasound evaluation included herniation contents and size, and the detection of other anomalies. Nine of 40 consecutive fetuses had abnormal karyotypes: trisomy 18 (n = 5), trisomy 13 (n = 3), 47,XXX (n = 1). Only 1/25 with an extracorporeal liver versus 8/15 with an intracorporeal liver had abnormal chromosomes [P = 0.0006, RR = 0.14 (0.02 < RR < 0.9)]. Small defects (< 3 cm) were associated with abnormal karyotypes [P = 0.01, RR = 4.7 (1.4 < RR < 15.6)]. Finding concurrent malformations was highly associated with chromosomal anomalies [P = 0.00004, RR = 4.4 (2.3 < RR < 8.5)]. The presence of associated malformations, an intracorporeal liver, and a small herniation size are highly suggestive of an associated abnormal karyotype.

Aplasia cutis congenita: a rare cause of elevated alpha-fetoprotein levels.

We present a catastrophic case of aplasia cutis congenita from a pregnancy complicated by elevated maternal serum and amniotic fluid alpha-fetoprotein levels and a positive acetylcholinesterase. Delivery occurred at 27 weeks 1 day after premature rupture of membranes with chorioamnionitis. The neonate lacked > 90% of its skin and died.