Does change in device detected frequency of non-sustained or diverted episodes serve as a marker for inappropriate shock therapy? Analyses from the INTRINSIC RV and ALTITUDE-REDUCES Trials.

AIMS: Implantable cardioverter-defibrillators (ICDs) treat ventricular tachycardia or fibrillation but may also deliver unnecessary shocks. We sought to determine if the frequency of ICD-detected non-sustained or diverted (NSD) episodes increases before appropriate or inappropriate ICD shocks. METHODS AND RESULTS: We evaluated NSD episodes in the INTRINSIC RV Trial and their relationship to ICD shocks (appropriate and inappropriate). Time from NSD to shock was analysed. Results were validated by utilizing 1495 adjudicated ICD and cardiac resynchronization therapy-defibrillator shocks following NSD episodes collected through the LATITUDE remote monitoring system as part of the ALTITUDE-REDUCES Study. In INTRINSIC RV, 185 participants received 373 shocks; 148 had at least 1 NSD episode. Non-sustained or diverted frequency increased 24 h before the first shock for those receiving an inappropriate (P < 0.01) but not an appropriate shock (P = 0.17). Patients with NSD episodes within 24 h of a shock were significantly more likely to receive inappropriate therapy [odds ratio (OR) = 3.12, P < 0.01]. At the receiver operator curve determined optimal cutoff, an NSD episode within 14 min before shock strongly predicted inappropriate therapy (sensitivity 48%, specificity 91%; OR = 8.8, and P < 0.001). The 14 min cut-off evaluated on an independent dataset of 1495 shock episodes preceded by an NSD in the ALTITUDE-REDUCES Study confirmed these results (sensitivity = 47%, specificity = 85%, OR = 5.0, and P < 0.001). CONCLUSION: Device-detected NSD episodes increase before inappropriate but not appropriate shocks. Novel alerts or automated algorithms based on NSD episodes may reduce inappropriate shocks.

Depression but not seizure factors or quality of life predicts suicidality in epilepsy.

The objective of this study was to determine prevalence and predictive risk factors of suicidality in a large sample of epilepsy outpatients. We prospectively examined 193 consecutive adult epilepsy outpatients for depression, including suicidal ideation. Demographic and epilepsy factors, medication toxicity and health-related quality of life were also evaluated. The prevalence of suicidal ideation within the past two weeks was 11.9%. Although medication toxicity, health-related quality of life and BDI scores were each associated with suicidal ideation in the bivariate analyses, only the BDI remained significant in the logistic regression analysis. About one-fourth of the subjects with suicidal ideation had no significant symptoms of depression. Recent thoughts of suicide are a common occurrence in the outpatient epilepsy clinic setting, but these are not predicted by gender, age, seizure factors, medication toxicity or self-perceived quality of life. Although depression is associated with suicidal ideation, about one-fourth of the suicidal subjects were euthymic or only mildly depressed.

Noise, artifact, and oversensing related inappropriate ICD shock evaluation: ALTITUDE noise study.

BACKGROUND: Approximately 12-21% of implantable cardioverter defibrillator (ICD) patients receive inappropriate shocks. We sought to determine the incidence and causes of noise/artifact and oversensing (NAO) resulting in ICD shocks. METHODS: A random sample of 2,000 patients who received ICD and cardiac resynchronization therapy defibrillator shocks and were followed by a remote monitoring system was included. Seven electrophysiologists analyzed stored electrograms from the 5,279 shock episodes. Episodes were adjudicated as appropriate or inappropriate shocks. RESULTS: Of the 5,248 shock episodes with complete adjudication, 1,570 (30%) were judged to be inappropriate shocks. Of these 1,570, 134 (8.5%) were a result of NAO. The 134 NAO episodes were determined to be due to external noise in 76 (57%), lead connector-related in 37 (28%), muscle noise in 11 (8%), oversensing of atrium in seven (5%), T-wave oversensing in two (2%), and other noise in one (1%). The ICD shock itself resulted in a marked decrease in the level of noise in 60 of 134 (45%) NAO episodes, and the magnitude of this effect varied with the type of NAO (58% for external noise, 35% for muscle, 27% for lead/connector, and 0% for oversensing; P = 0.03). There was no significant difference in NAO likelihood based on type of lead (integrated bipolar 89/1,802 vs dedicated bipolar 9/140, P = 0.67). CONCLUSIONS: External noise and lead/connector noise were the primary causes, while T-wave oversensing was the least common cause of NAO resulting in ICD shock. Noise/artifact decreased immediately after a shock in nearly half of episodes. The specific ICD lead type did not impact the likelihood of NAO.

Long-term outcome after ICD and CRT implantation and influence of remote device follow-up: the ALTITUDE survival study.

BACKGROUND: Outcome data for patients receiving implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) devices treated outside of clinical trials are lacking. No clinical trial has evaluated mortality after device implantation or after shock therapy in large numbers of patients with implanted devices that regularly transmit device data over a network. METHODS AND RESULTS: Survival status in patients implanted with ICD and CRT devices across the United States from a single manufacturer was assessed. Outcomes were compared between patients followed in device clinic settings and those who regularly transmit remote data collected from the device an average of 4 times monthly. Shock delivery and electrogram analysis could be ascertained from patients followed on the network, enabling survival after ICD shock to be evaluated. One- and 5-year survival rates in 185,778 patients after ICD implantation were 92% and 68% and were 88% and 54% for CRT-D device recipients. In 8228 patients implanted with CRT-only devices, survival was 82% and 48% at 1 and 5 years, respectively. For the 69,556 ICD and CRT-D patients receiving remote follow-up on the network, 1- and 5-year survival rates were higher compared with those in the 116,222 patients who received device follow-up in device clinics only (50% reduction; P<0.0001). There were no differences between patients followed on or off the remote network for the characteristics of age, gender, implanted device year or type, and economic or educational status. Shock therapy was associated with subsequent mortality risk for both ICD and CRT-D recipients. CONCLUSIONS: Survival after ICD and CRT-D implantation in patients treated in naturalistic practice compares favorably with survival rates observed in clinical trials. Remote follow-up of device data is associated with excellent survival, but arrhythmias that result in device therapy in this population are associated with a higher mortality risk compared with patients who do not require shock therapy.

Real world evaluation of dual-zone ICD and CRT-D programming compared to single-zone programming: the ALTITUDE REDUCES study.

INTRODUCTION: We evaluated the frequency of appropriate and inappropriate shocks and survival in patients using dual-zone programming versus single-zone programming. METHODS AND RESULTS: For the ALTITUDE REDUCES study, patients were followed for 1.6 ± 1.1 years. The 12-month incidence of any shock was lower for dual-versus single-zone programmed detection at rates ≤170 bpm and between 170-200 bpm (P < 0.001). Appropriate shock rates at 1 year were also lower with dual-zone programming in these rate intervals (single zone 9.1%, 5.4%, P < 0.001, dual zone 6.7%, 4.7%, P < 0.02). There were no detectable differences between single- and dual-zone shock incidence at detection rates ≥ 200 bpm (P = 0.14). Inappropriate shock incidence was less with dual- versus single-zone detection at all detect rates <200 bpm, but not at rates ≥200 bpm (P < 0.001, P = 0.37). The lowest risk of appropriate and inappropriate shock was associated with dual-zone programming and detection rates ≥200 bpm (2.1%). Dual-zone detection was associated with more nonsustained and diverted therapy episodes but these patients did not have an increased risk of death compared to patients with single-zone programming. Patients programmed to low detection rate, single-zone detection and shock-only therapy also had the highest preshock mortality risk (P = 0.05). CONCLUSIONS: Shock incidence is lowest with either single- or dual-zone detection ≥200 bpm. For detection rates <200 bpm, dual-zone programming is associated with a reduction in the incidence of total shocks, appropriate shocks, and inappropriate shocks.

Implantable cardioverter defibrillator electrogram adjudication for device registries: methodology and observations from ALTITUDE.

BACKGROUND: The increasing use of remote monitoring with the associated large retrievable databases provides a unique opportunity to analyze observations on implantable cardioverter-defibrillator (ICD) therapies. Adjudication of a large number of stored ICD electrograms (EGMs) presents a unique challenge. The ALTITUDE study group was designed to use the LATITUDE remote monitoring system to evaluate ICD patient outcomes across the United States. METHODS AND RESULTS: Of 81,081 patients on remote monitoring, a random sample of 2,000 patients having 5,279 shock episodes was selected. The ALTITUDE EGM review committee was comprised of seven electrophysiologists from four institutions. An online EGM adjudication system was designed. Episodes were classified as appropriate (70% of shock episodes) or inappropriate ICD therapies (30%). Light's Kappa was used to assess agreement. Interobserver and intraobserver Kappa scores for dual-chamber ICDs were 0.84 (0.71-0.91) and 0.89 (0.82-0.95), consistent with substantial agreement. Interobserver and intraobserver Kappa scores for single-chamber ICDs were 0.61 (0.54-0.67) and 0.69 (0.59-0.79). The rhythm categories of "nonsustained arrhythmia" and "polymorphic and monomorphic ventricular tachycardia" resulted in the greatest degree of discordant adjudication between reviewers. CONCLUSIONS: This method of adjudication of a large volume of stored EGM data prior to device therapies will allow new observations in regards to device performance and has the potential to improve device programming and design. There was substantial interreviewer agreement for rhythm classification. Agreement was greater for dual-chamber compared to single-chamber devices, indicating the atrial lead adds diagnostic value in rhythm interpretation.

Global assessment of nitrogen deposition effects on terrestrial plant diversity: a synthesis.

Atmospheric nitrogen (N) deposition is a recognized threat to plant diversity in temperate and northern parts of Europe and North America. This paper assesses evidence from field experiments for N deposition effects and thresholds for terrestrial plant diversity protection across a latitudinal range of main categories of ecosystems, from arctic and boreal systems to tropical forests. Current thinking on the mechanisms of N deposition effects on plant diversity, the global distribution of G200 ecoregions, and current and future (2030) estimates of atmospheric N-deposition rates are then used to identify the risks to plant diversity in all major ecosystem types now and in the future. This synthesis paper clearly shows that N accumulation is the main driver of changes to species composition across the whole range of different ecosystem types by driving the competitive interactions that lead to composition change and/or making conditions unfavorable for some species. Other effects such as direct toxicity of nitrogen gases and aerosols, long-term negative effects of increased ammonium and ammonia availability, soil-mediated effects of acidification, and secondary stress and disturbance are more ecosystem- and site-specific and often play a supporting role. N deposition effects in mediterranean ecosystems have now been identified, leading to a first estimate of an effect threshold. Importantly, ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase, in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas. Critical loads are effect thresholds for N deposition, and the critical load concept has helped European governments make progress toward reducing N loads on sensitive ecosystems. More needs to be done in Europe and North America, especially for the more sensitive ecosystem types, including several ecosystems of high conservation importance. The results of this assessment show that the vulnerable regions outside Europe and North America which have not received enough attention are ecoregions in eastern and southern Asia (China, India), an important part of the mediterranean ecoregion (California, southern Europe), and in the coming decades several subtropical and tropical parts of Latin America and Africa. Reductions in plant diversity by increased atmospheric N deposition may be more widespread than first thought, and more targeted studies are required in low background areas, especially in the G200 ecoregions.

Predictors of early mortality in implantable cardioverter-defibrillator recipients.

AIMS: Multiple trials have shown that implantable cardioverter defibrillators (ICDs) prolong survival in secondary and primary prevention populations. However, in spite of the efficacy of these devices in terminating life-threatening arrhythmias, total mortality remains high. METHODS AND RESULTS: We evaluated 1703 patients (mean age: 67 +/- 12 years, 82% male) with conventional ICD indications, who were enrolled and followed between 2001 and 2004 at 128 US centres. Patients were followed for up to a year, and vital status was obtained for 1655 patients (97%, median follow-up: 377 days). There were 183 deaths within 1 year of ICD implantation (1-year mortality rate: 16%). Predictors of mortality included a history of atrial fibrillation (AF, P < 0.0001), diabetes (P = 0.0001), failure to use cholesterol-lowering medications (P < 0.001), use of digitalis and derivatives (P < 0.0001), use of diuretics (P < 0.0001), low body mass index (BMI, P < 0.0001), increasing age (P < 0.0001), low left ventricular ejection fraction (P < 0.0001), low activity hours (P < 0.0001), elevated resting heart rate (P = 0.014), low mean arterial pressure (MAP, P = 0.007), and poor functional status (New York Heart Association class, P < 0.0001). In multivariate modelling, AF (P < or = 0.001), diabetes (P = 0.004), BMI (P = 0.001), MAP (P = 0.040), and functional class (P = 0.006) predicted mortality. CONCLUSION: In this population undergoing ICD implantation, poor functional status, low MAP, diabetes, low BMI, and AF were strongly associated with death within a year.

Comorbidity between temporal lobe epilepsy and depression: a [18F]MPPF PET study.

Brain and brainstem changes of serotoninergic 5-hydroxytryptophan (5-HT)(1A) receptor density have been reported in patients with major depressive disorder as well as in patients with temporal lobe epilepsy (TLE), using PET and the selective antagonist radiotracers [(11)C]WAY-100635 or [(18)F]FC-WAY. We used a distinct 5-HT(1A) antagonist, [(18)F]MPPF, whose binding potential depends on both receptor density and extracellular serotonin concentration, in 24 patients with drug-resistant TLE and MRI evidence of hippocampal sclerosis but without prior antidepressant exposure. Their Beck Depression Inventory (BDI-2) score ranged from 0 to 34, with nine patients having a score >11. We used a simplified reference tissue model, statistical parametric mapping and anatomical regions of interest (ROIs) to correlate parametric images of [(18)F]MPPF BP with the total BDI score and its four subclasses. The total BDI score, as well as symptoms of psychomotor anhedonia and negative cognition, correlated positively with [(18)F]MPPF BP in the raphe nuclei and in the insula contralateral to seizure onset, whereas somatic symptoms correlated positively with [(18)F]MPPF binding potential in the hippocampal/parahippocampal region ipsilateral to seizure onset, the left mid-cingulate gyrus and the inferior dorsolateral frontal cortex, bilaterally. We confirm an association of depressive symptoms in TLE patients with changes of the central serotoninergic pathways, in particular within the raphe nuclei, insula, cingulate gyrus and epileptogenic hippocampus. These changes are likely to reflect lower extracellular serotonin concentration in more depressed patients, with an upregulation of receptors a less likely alternative.

Frequency, duration, and predictors of newly-diagnosed atrial fibrillation following dual-chamber pacemaker implantation in patients without a previous history of atrial fibrillation.

The Silent Atrial Fibrillation Detection With Stored EGMs (SAFE) registry is the first prospective study to characterize the incidence, duration, and predictors of atrial high-rate episodes (AHREs) in patients without previous clinically diagnosed atrial fibrillation after dual-chamber pacemaker implantation. Patients underwent in-clinic device interrogation at 2 weeks and then 3, 6, and 12 months after implantation. An AHRE was defined as an atrial tachyarrhythmia with an atrial rate > or =180 beats/min lasting > or =5 minutes. During the first month after pacemaker implantation, AHREs were identified in 68 patients (4.6%). Thirty-four of these patients (50%) did not have AHREs beyond the first month after implantation; these patients were older than those who continued to have AHREs (79 +/- 9 vs 74 +/- 12 years, p = 0.05). Within the first 6 months after pacemaker implantation, 150 patients (10%) experienced a total of 455 AHREs, of which only 28 (6%) prompted clinical visits. The 6-month freedom from an AHRE was 82%. Overall, 75% of patients with AHREs had multiple episodes; most AHREs lasted 5 to 60 minutes. In conclusion, 6 months after dual-chamber pacemaker implantation, 10% of patients experienced > or =1 AHRE, usually lasting 5 to 60 minutes. Some patients had AHREs only within the first 30 days after implantation, suggesting the possibility of transient atrial proarrhythmia related to lead insertion.

Marked QRS complex abnormalities and sodium channel blockade by propoxyphene reversed with lidocaine.

The opiate analgesic propoxyphene produces cardiac toxicity when taken in overdose. We recently observed a patient with propoxyphene overdose in whom marked QRS widening was reversed by lidocaine. The reversal is apparently paradoxical as both agents block the inward sodium current (INa). We examined possible mechanisms of the reversal by measuring INa in rabbit atrial myocytes during exposure to propoxyphene and the combination of propoxyphene and lidocaine (60 and 80 microM, respectively). Propoxyphene caused use-dependent block of INa during pulse train stimulation. Block recovered slowly with time constants of 20.8 +/- 3.9 s. Block during lidocaine exposure recovered with time constants of 2-3 s. During exposure to the mixture, block recovered as a double exponential. The half time for recovery during exposure to the mixture was 1.6 +/- .9 s compared with a half-time of 14.3 +/- 2.9 s during exposure to propoxyphene alone. During pulse train stimulation, less steady-state block was observed during exposure to the mixture than during exposure to propoxyphene alone when the interval between pulses was greater than 0.95 s. Both drugs compete for a common receptor during the polarizing phase. The more rapid dissociation of lidocaine during the recovery period leads to less block during the mixture than during exposure to propoxyphene alone. The experiments suggest a mechanism for reversal of the cardiac toxicity of drugs which have slow unbinding kinetics.

Racial disparity in the utilization of implantable-cardioverter defibrillators among patients with prior myocardial infarction and an ejection fraction of

Age-adjusted sudden cardiac death rates are highest for black patients compared with other racial groups. The prophylactic implantation of an implantable cardioverter-defibrillator (ICD) provides a significant reduction in sudden cardiac death and overall mortality in patients after myocardial infarctions with significant left ventricular systolic dysfunction. The purpose of this study was to determine whether black patients with left ventricular systolic dysfunction were less likely than white patients to receive ICDs for the primary prevention of sudden cardiac death. Data from the National Registry to Advance Heart Health (ADVANCENT) were analyzed to determine which patients with histories of myocardial infarctions and ejection fractions

Prognostic value of heart rate variability footprint and standard deviation of average 5-minute intrinsic R-R intervals for mortality in cardiac resynchronization therapy patients.

BACKGROUND: Cardiac resynchronization therapy devices provide effective therapy for heart failure. Heart rate variability (HRV) parameters in the device such as HRV footprint and SD of average 5-minute intrinsic R-R intervals (SDANN) are related to autonomic function and may be used to identify patients with a higher risk of mortality. METHODS: We examined the relationship between HRV and mortality in a prospective cohort study. The 842 patients (mean age, 67.7 +/- 11.2; 23.5 % female; New York Heart Association class III, 88.6%; class IV, 11.4%) included in the analysis were implanted with a cardiac resynchronization therapy with defibrillation device and had baseline HRV measurements available. RESULTS: During a median of 11.6 months of follow-up, 7.8% (66/842) of patients died. Heart rate variability footprint and SDANN were significant predictors of mortality (all P < .05); patients with lower HRV values were at greater risk for death, compared with patients with higher HRV values. Heart rate variability changes over time tended to predict the risk of mortality in follow-up (P = nonsignificant); patients with low baseline HRV and small changes in HRV during the follow-up period were at the highest risk for death (7% mortality for SDANN and 8.9% for HRV footprint), and patients with high baseline HRV and large changes in HRV were at the lowest risk (1.5% mortality for SDANN and 2.4% for HRV footprint). Results were consistent when adjusted for age, sex, body mass index, and diastolic blood pressure. CONCLUSIONS: Continuously measured device HRV parameters provide prognostic information about patient mortality that may be helpful for risk stratification.

Epidemiological and medical aspects of epilepsy in the elderly.

Both the incidence and prevalence of epilepsy are high among the elderly. Cerebrovascular disease is the most common underlying cause, although as many as 25-40% of new epilepsy cases in the elderly have no obvious underlying etiology. Status epilepticus appears to occur more frequently in individuals greater than 60 years, and the morbidity and mortality of status epilepticus are significantly greater in this age group. Elderly patients with seizures, particularly complex partial seizures, present differently than younger adults, which can lead to misdiagnosis. Post-ictal confusion may last as long as 1-2 weeks in an elderly patient, as opposed to minutes in younger individuals. Adverse events are similar in symptomatology, but are more common in elderly patients and occur at lower doses and plasma drug concentrations. Neuropsychiatric disorders, such as depression and anxiety, are common in elderly patients with epilepsy, although often under-diagnosed and inadequately treated. The risk of osteoporosis is high among elderly women taking antiepileptic drugs, which underscores the importance of assessing bone health and treatment in this group. Management of the older patient with epilepsy requires an understanding of the etiologies and the medical and psychological aspects unique to this age group.

Efficacy and temporal stability of reduced safety margins for ventricular defibrillation: primary results from the Low Energy Safety Study (LESS).

BACKGROUND: Traditionally, a safety margin of at least 10 J between the maximum output of the pulse generator and the energy needed for ventricular defibrillation has been used because lower safety margins were associated with unacceptably high rates of failed defibrillation and sudden cardiac death. The Low Energy Safety Study (LESS) was a prospective, randomized assessment of the safety margin requirements for modern implantable cardioverter-defibrillator (ICD) systems. METHODS AND RESULTS: A total of 636 patients undergoing initial ICD implantation with a dual-coil lead and active pulse generator were evaluated. The defibrillation threshold (DFT) and enhanced DFT (DFT+ and DFT++) were measured using a modified step-down protocol. Conversion testing of induced ventricular fibrillation before discharge, at 3 months, and at 12 months was performed, as was randomization to chronic programming at either 2 steps above DFT++ or maximal output. The induced ventricular fibrillation data had conversion success rates of 91.4%, 97.9%, 99.1%, 99.6%, and 99.8% for safety margins of 0, 1, 2, 3, and 4 steps above the DFT++, respectively. A margin of 4 to 6 J was adequate to maintain high conversion success over time (98.9% before discharge versus 99.2% at 12 months; P=NS). Over a mean follow-up of 24+/-13 months, conversion of spontaneously occurring ventricular tachyarrhythmias >200 bpm was identical (97.3%), despite a safety margin difference of 5.2+/-1.1 J for the 2-step group versus 20.8+/-4.2 J for maximal output. CONCLUSIONS: With a rigorous implantation algorithm, a safety margin of about 5 J is adequate for safe implantation of modern ICD systems.

The buddy wire technique: accessing lateral coronary veins while maintaining coronary sinus position.

There is compelling data to place the coronary sinus lead (CSL) in a lateral or posterolateral tributary. Coronary sinus venography often demonstrates the absence of easily accessible lateral veins or those with sufficient size to accommodate the CSL. The operator may choose to deploy the CSL in the anterior vein but publications and experience highlight the lack of resynchronization benefit when the CSL is deployed in this location. There is often a posterolateral vessel or the middle cardiac vein (MCV) originating from near the coronary sinus (CS) os. These vessels require the operator to pull the CS guide essentially out of the CS to allow successful access. Cannulation of the coronary sinus (CS) is often challenging, and the risk of losing access to the CS may dissuade the implanter from attempting access to a vessel near the CS os. We describe a technique to access vessels near the CS os while maintaining secure position in the main body of the CS.

Ictal amaurosis: MRI, EEG, and clinical features.

We studied seven consecutive patients who experienced amaurosis as a prominent feature of their seizures. The mean age of seizure onset was 4 years. Six patients had MRI abnormalities including ischemic, traumatic, and space-occupying lesions, with five limited to the parietal-occipital region. Six patients had unilateral, posterior interictal spike and slow wave complexes. Four patients experienced severe postictal headache and nausea. Absence of a family history of seizures distinguished the patients with MRI lesions from previously presented series of benign occipital lobe epilepsy. We conclude that the constellation of ictal amaurosis, occipital paroxysms, and postictal migrainous symptoms does not necessarily signify a benign, nonlesional epilepsy; MRI is recommended for such patients without a family history of similar seizures.

Significance of spontaneous epileptiform abnormalities associated with a photoparoxysmal response.

Spontaneous epileptiform abnormalities (SEAs) are reported to occur in up to 65% of patients with a photoparoxysmal response (PPR). Although the PPR is usually assumed to indicate primary generalized epilepsy, the clinical significance of associated SEAs is not known. We conducted the first study designed to correlate seizure classification with type of SEA in photosensitive patients. We examined seizure classifications and SEAs in 115 consecutive patients who had a PPR. A PPR was the only epileptiform abnormality in 47 patients (41%). Twenty-seven patients (24%) had focal SEAs and 41 (36%) had only generalized SEAs. Seventeen patients (15%) had partial seizures and 40 (35%) had only generalized seizures. Seizure classification was strongly associated with type of SEA (p < 0.0001). Patients with focal SEAs tended to have partial seizures, while patients with generalized SEAs tended to have only generalized tonic-clonic or absence seizures. Also, the presence of SEAs was significantly associated with a history of seizures (p < 0.0001), compared with patients who had a PPR but no SEAs. Although the PPR is often presumed to signify primary generalized epilepsy, most patients with a PPR and focal SEAs have partial seizures.

Ifosfamide causes a diazepam-sensitive encephalopathy.

An encephalopathy characterized by confusion, stupor, and mutism frequently occurs during administration of the chemotherapeutic drug ifosfamide (IFX). We investigated two patients who developed encephalopathy during IFX infusion. Both exhibited a rapid and near-complete restoration of baseline mental status functioning concurrent with EEG improvement after administration of intravenous diazepam. We recommend an EEG and trial of benzodiazepines in patients with IFX encephalopathy.

Congenital porencephaly and hippocampal sclerosis. Clinical features and epileptic spectrum.

We studied clinical features and seizure localization in 14 patients with porencephaly and intractable seizures. Perinatal complications were present in nine patients, childhood febrile convulsions in two, congenital hemiparesis in 12, and intellectual impairment in seven. Ten patients had psychoparetic complex partial seizures (CPS), three had sensorimotor simple partial seizures, and one had generalized tonic-clonic seizures. Surface EEG showed temporal onset in nine patients (one bitemporal) and extratemporal onset in four. MRI showed porencephaly in the distribution of the middle cerebral artery in eight patients, posterior cerebral in three, internal carotid in one, and multiple vessels in two. MR-based volumetry revealed hippocampal formation atrophy in 13 patients (eight unilateral and five bilateral) and amygdalar atrophy in 10 patients (nine unilateral and one bilateral). Hippocampal formation atrophy was concordant with CPS semiology in 10 patients (71%) and with EEG temporal localization in nine patients. Two patients had pathologic confirmation of mesial temporal sclerosis and were seizure free after temporal lobectomy. We conclude that mesial temporal sclerosis often coexists with porencephaly and is the likely seizure focus in the presence of concordant electroclinical data. This recognition implies that effective surgical intervention can be offered to certain patients with porencephaly-related seizure disorders. The dual pathology and association with perinatal cerebral vascular occlusion suggest a common ischemic pathogenesis.