Outcomes of pregnancy associated with antiepileptic drugs.

OBJECTIVE: To determine whether exposure to antiepileptic drugs during pregnancy is associated with poor fetal outcomes (anomalies and death) and to assess the relative risks with phenobarbital, phenytoin sodium, and carbamazepine. DESIGN: The design was a prospective case-control cohort study of pregnant women with epilepsy and their offspring. Outcomes were compared with those of a control group of 355 healthy women and their offspring. SETTING: The obstetrics service at Los Angeles County/University of Southern California Medical Center, Los Angeles, a large, inner-city, teaching hospital. PATIENTS: Two hundred eleven subjects who were pregnant during the years 1987 through 1990, 174 of whom were delivered of infants, were available for analysis. A control group of 355 healthy women and their offspring from the same hospital were randomly selected from a computerized database. INTERVENTION: None. MAIN OUTCOME MEASURE: Anomalies and fetal death were the primary outcome measures. RESULTS: Offspring of women with epilepsy who were exposed to antiepileptic drugs had a higher rate of fetal death and anomalies than did the control population (P = .001). Abnormal outcomes were associated with the three major antiepileptic drugs (carbamazepine, phenytoin, and phenobarbital). In terms of abnormal outcome (death and anomalies), phenobarbital was associated with the highest relative risk, phenytoin with intermediate relative risk, and carbamazepine with the lowest relative risk (P = .019). Numbers were insufficient for assessment of risk associated with valproic acid. CONCLUSION: All three major antiepileptic drugs (phenobarbital, phenytoin, and carbamazepine) are associated with an increased risk of fetal death and anomalies. We found phenobarbital to be most associated with poor pregnancy outcome.

Predictive value of P300 event-related potentials compared with EEG and somatosensory evoked potentials in non-traumatic coma.

Developments in ethical decision making are increasing demand for more accurate predictions of outcome in coma. New neurophysiologic tests are needed to improve the ability to predict awakening as well as poor outcome. We have recently reported that the P300 event-related potential (P300) correlates with awakening and depth of nontraumatic coma. In this companion study, the predictive value of the P300 was compared with median nerve somatosensory evoked potentials (SEP) and EEG in 20 patients in non-traumatic coma. We also evaluated the predictive value of a simplified grading scale for both the EEG and SEP (the USC SEP scale and USC EEG scale). The presence of a P300 was significantly associated with higher Glasgow coma scores (GCS) and awakening. Severe abnormalities of the somatosensory evoked potentials significantly correlated with the absence of awakening and a low GCS. Moderate abnormalities of the SEP were significantly associated with awakening and higher GCS scores. The EEG was significantly associated with GCS score and severe abnormalities of the EEG were predictive of the absence of awakening and very low GCS scores. The data indicates that the P300 and SEP are more effective than the EEG in predicting awakening, and that the SEP and EEG are more effective than the P300 in predicting poor outcome. We conclude that, in addition to EEG and SEP, the P300 should be considered in the prognostic evaluation of patients in nontraumatic coma. Further, simplified scales for the EEG and SEP are predictive of depth of coma and outcome.

Lidocaine in refractory status epilepticus: confirmation of efficacy with continuous EEG monitoring.

Lidocaine was efficacious in 2 patients with refractory status epilepticus (RSE) unresponsive to several antiepileptic drugs (AEDs), including high-dose barbiturates. We confirmed the efficacy of lidocaine with, for the first time in adults, continuous EEG monitoring. Lidocaine, when properly used, may be a treatment option in RSE.

Carbamazepine-induced antinuclear antibodies and systemic lupus erythematosus-like syndrome.

A 20-year-old woman developed a systemic lupus erythematosus (SLE)-like syndrome and a positive antinuclear antibody (ANA) soon after initiation of carbamazepine (CBZ) therapy. Symptoms and serology became normal after CBZ was discontinued. CBZ-induced SLE is an important but underecognized phenomenon.

Early prognosis in anoxic coma. Reliability and rationale.

As desirable as it might be to predict early in the course of coma whether a patient will do well or poorly, all studies of coma prognosis are plagued by inherent methodologic problems that tend to diminish the utility of the derived criteria: especially the tendency of poor prognoses to be self-fulfilling, the rapid drop-off in patient population due to death from nonneurologic causes, and the need to lump, for the sake of statistical significance, outcome categories that ought to be kept distinct for purposes of ethical decision making. Even for a methodologically ideal study, if 100 per cent of the N patients fulfilling a particular criterion experienced the same poor outcome, the probability of a false prediction of poor outcome in the next patient meeting that criterion is approximately 1/(N + 2), which is hardly negligible for a realistically sized study. Moreover, there is a 50 per cent chance of at least one false-positive prediction among the next (N + 1) patients fulfilling the criterion. Given this inherent unreliability of early predictors for individual patients, given that decisions to continue life support are reversible, whereas decisions to withdraw it are usually not, and given that the death of a patient with potential for recovery is a more serious error than the (typically) transient prolongation of life of a patient destined soon to die anyway or (much less commonly) to remain in a chronic vegetative state, it would seem prudent to continue life support for all patients during the first few weeks or months of coma or vegetative state, regardless of early indicators of poor outcome. Early prognostication can still serve other useful purposes, however, including the counseling of families, triage and DNR decisions, and future clinical investigations of brain-resuscitative measures.

Ifosfamide encephalopathy.

We describe a case of reversible encephalopathy caused by the recently released anticancer drug Ifosfamide. The clinical course, role of EEG in monitoring and predicting encephalopathy, and putative mechanism of neurotoxicity is discussed. Short infusion times and/or prior CNS disease may increase the risk of encephalopathy.