Long-term outcome of vagus nerve stimulation for drug-resistant epilepsy using continuous assessment, with a note on mortality.

PURPOSE: To examine the outcome of vagus nerve stimulation (VNS) for drug-resistant epilepsy using data from a National Health Service VNS clinic. METHODS: Clinical records of patients implanted with VNS for epilepsy between1995 and 2010 were examined. Patients were selected for study who had at least one year of therapeutic stimulation (minimum 1 mA stimulator current) and follow-up by our service with analysable electronic records, providing continuous assessment of seizure control during available follow-up. Seizure status at each attendance was assessed and graded 1-4 (1=seizure free or <5 seizures/year; 2 =≥50%reduction in seizure frequency; 3=<50% reduction; 4=no improvement compared to baseline). Responders were those whose grades improved consistently (Grades 1,2 and 3). RESULTS: Of 464 patients, 171 fulfilled the inclusion criteria and were divided into three groups: a) Responders (n = 81); b) non-responders (n = 80) and c) others (n = 10), the latter showing a late step-wise change (six improved; four deteriorated). After initial ramping up of current, groups were very stable over subsequent periods varying from one to 12 years (median 3.8 years). Sixteen patients died, 10 of non-epilepsy causes with 6 epilepsy-related deaths. There was a significant relation between epilepsy-related deaths and response (p < 0.00001). Patients with longer time as non-responders had more likelihood of suffering an epilepsy death than responders, though numbers were small. CONCLUSION: This study shows that meaningful data can be obtained retrospectively from routine clinic records. In this cohort about half of patients treated with VNS responded and the response generally remaining stable over time.

Role of single pulse electrical stimulation (SPES) to guide electrode implantation under general anaesthesia in presurgical assessment of epilepsy.

PURPOSE: Single-pulse electrical stimulation (SPES) during intracranial recordings is part of the epilepsy presurgical evaluation protocol at King's College Hospital (London). Epileptiform responses correlated to the stimulus (delayed responses - DRs) tend to occur in areas of seizure onset, thereby allowing interictal identification of epileptogenic cortex in patients suffering refractory epilepsy. This preliminary study investigated the validity of SPES in the operating theatre under general anaesthesia (GA) during the implantation procedure, aiming to improve the positioning of intracranial electrodes. METHODS: Twelve drug-resistant epilepsy patients implanted with depth and/or subdural electrodes were studied. SPES (1 ms pulses, 4-8 mA, 0.2 Hz) was performed during both intra-operative electrode implantation under GA and chronic intracranial ECoG recordings, and the two recordings were compared in terms of cortical responses produced by stimulation and their electrode location. RESULTS: In 8/12 patients, SPES during chronic recordings produced DRs positively correlated to seizure onset and/or early seizure propagation areas. Of those eight patients, four showed DRs during electrode implantation under GA over the same electrode contacts. Among the four patients without DR during GA, three had continuous localized spontaneous epileptiform discharges, which made interpretation of SPES responses unreliable. CONCLUSION: This study showed that, under GA, DRs can be reliably replicated, without false positive epileptiform responses to SPES, although the method's sensitivity is greatly reduced by spontaneous discharges. Results support SPES as a complementary technique that can be used to improve electrode placement during epilepsy surgery when no profound interictal activity is present.

DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge.

We have previously shown that macaques vaccinated with DNA vectors expressing SIVmac239 antigens developed potent immune responses able to reduce viremia upon high-dose SIVmac251 challenge. To further improve vaccine-induced immunity and protection, we combined the SIVmac239 DNA vaccine with protein immunization using inactivated SIVmac239 viral particles as protein source. Twenty-six weeks after the last vaccination, the animals were challenged intrarectally at weekly intervals with a titrated dose of the heterologous SIVsmE660. Two of DNA-protein coimmunized macaques did not become infected after 14 challenges, but all controls were infected by 11 challenges. Vaccinated macaques showed modest protection from SIVsmE660 acquisition compared with naïve controls (P = 0.050; stratified for TRIM5α genotype). Vaccinees had significantly lower peak (1.6 log, P = 0.0048) and chronic phase viremia (P = 0.044), with 73% of the vaccinees suppressing viral replication to levels below assay detection during the 40-wk follow-up. Vaccine-induced immune responses associated significantly with virus control: binding antibody titers and the presence of rectal IgG to SIVsmE660 Env correlated with delayed SIVsmE660 acquisition; SIV-specific cytotoxic T cells, prechallenge CD4(+) effector memory, and postchallenge CD8(+) transitional memory cells correlated with control of viremia. Thus, SIVmac239 DNA and protein-based vaccine protocols were able to achieve high, persistent, broad, and effective cellular and humoral immune responses able to delay heterologous SIVsmE660 infection and to provide long-term control of viremia. These studies support a role of DNA and protein-based vaccines for development of an efficacious HIV/AIDS vaccine.

Value of scalp delayed rhythmic ictal transformation (DRIT) in presurgical assessment of temporal lobe epilepsy.

OBJECTIVES: To estimate the localising and lateralising value of delayed rhythmic ictal transformation (DRIT) on the scalp EEG during presurgical assessment for temporal lobe epilepsy. METHODS: Two hundred and eighty eight seizures recorded simultaneously with scalp and foramen ovale (FO) electrodes were studied retrospectively in 110 patients. DRIT was defined as sustained regular rhythmic waveforms seen on scalp recordings after scalp seizure onset. The incidence and laterality of scalp DRIT was evaluated by comparison to FO electrodes. RESULTS: Scalp DRIT was seen in 192 seizures, 65% of which showed focal mesial temporal onset (FMTO) recorded by FO electrodes. FMTO onset was seen in 73% of the 122 seizures showing unilateral scalp DRIT, in 32% of the 62 seizures showing bilateral asymmetrical scalp DRIT, and in 14% of the seven seizures showing bilateral symmetrical DRIT on the scalp. Among the 89 seizures showing unilateral scalp DRIT and FMTO, both were ipsilateral in 70 seizures (79%). Among the 38 seizures showing bilateral asymmetrical DRIT and FMTO, the largest amplitude of scalp DRIT was ipsilateral to the FO onset in 27 seizures (71%). CONCLUSION: Two thirds of seizures showed unilateral scalp DRIT, which had a lateralising value of up to 79%. SIGNIFICANCE: Scalp DRIT is a reliable marker to lateralise seizure focus in patients without a focal seizure onset on the scalp EEG.