Seizure outcomes in people with drug-resistant focal epilepsy evaluated for surgery but do not proceed.

OBJECTIVE: To ascertain seizure outcomes in people with drug-resistant focal epilepsy considered for epilepsy surgery but who did not proceed. METHODS: We identified people discussed at a weekly presurgical epilepsy multi-disciplinary (MDT) meeting from January 2015 to December 2019 and in whom a decision not to proceed to surgery was made. Seizure outcomes were obtained from individuals, primary care physicians and attending neurologists at a minimum of 12 months following the not to proceed decision. RESULTS: We considered 315 people who did not proceed to surgery after evaluation. Nine died, and 25 were lost to follow-up. We included 281 people with a median follow-up of 2.4 (IQR 1.5-4) years. In total, 83 (30%) people reported that seizures had improved or resolved since the MDT meeting. Thirteen (5%) were seizure-free over the last 12 months of follow-up, 70 (25%) had experienced more than 50% reduction in seizure frequency, 180 (64%) had no meaningful change, and 18 (6%) reported a doubling of seizure frequency. Of the 53 (16%) who had vagal nerve stimulation, 19/53 (37%) reported more than 50% reduction in frequency, including one seizure-free. SIGNIFICANCE: The chances of seizure freedom with further medications and neurostimulation are low for people with drug-resistant focal epilepsy who have been evaluated for surgery and do not proceed, but improvement may still occur. Up to a quarter have a > 50% reduction in seizures, and one in twenty become seizure-free eventually. Trying additional anti-seizure medication and neurostimulation is worthwhile in this population.

Reasons for not having epilepsy surgery.

OBJECTIVE: This study was undertaken to determine reasons for adults with drug-resistant focal epilepsy who undergo presurgical evaluation not proceeding with surgery, and to identify predictors of this course. METHODS: We retrospectively analyzed data on 617 consecutive individuals evaluated for epilepsy surgery at a tertiary referral center between January 2015 and December 2019. We compared the characteristics of those in whom a decision not to proceed with surgical treatment was made with those who underwent definitive surgery in the same period. Multivariate logistic regression was performed to identify predictors of not proceeding with surgery. RESULTS: A decision not to proceed with surgery was reached in 315 (51%) of 617 individuals evaluated. Common reasons for this were an inability to localize the epileptogenic zone (n = 104) and the presence of multifocal epilepsy (n = 74). An individual choice not to proceed with intracranial electroencephalography (icEEG; n = 50) or surgery (n = 39), risk of significant deficit (n = 33), declining noninvasive investigation (n = 12), and coexisting neurological comorbidity (n = 3) accounted for the remainder. Compared to 166 surgically treated patients, those who did not proceed to surgery were more likely to have a learning disability (odds ratio [OR] = 2.35, 95% confidence interval [CI] = 1.07-5.16), normal magnetic resonance imaging (OR = 4.48, 95% CI = 1.68-11.94), extratemporal epilepsy (OR = 2.93, 95% CI = 1.82-4.71), bilateral seizure onset zones (OR = 3.05, 95% CI = 1.41-6.61) and to live in more deprived socioeconomic areas (median deprivation decile = 40%-50% vs. 50%-60%, p < .05). SIGNIFICANCE: Approximately half of those evaluated for surgical treatment of drug-resistant focal epilepsy do not proceed to surgery. Early consideration and discussion of the likelihood of surgical suitability or need for icEEG may help direct referral for presurgical evaluation.

Juvenile myoclonic epilepsy refractory to treatment in a tertiary referral center.

INTRODUCTION: Juvenile myoclonic epilepsy (JME) is an epileptic syndrome often regarded as one in which seizures are relatively easy to control. Individuals with JME, however, often require lifelong therapy to remain seizure-free, and a few have refractory epilepsy. We ascertained a population with JME and characterized a subgroup with refractory epilepsy. MATERIAL AND METHODS: We audited and reviewed clinical records of individuals diagnosed with JME identified via a sample of 6600 individuals in a clinical database from a specialized epilepsy clinic at a tertiary referral center. RESULTS: We identified 240 people with a diagnosis of JME (146 females), with a mean age at seizure onset of 14.2years (SD: 4.5), and a mean age at diagnosis of 15.6years (SD: 4.9). Clinical phenotypes seen were classic JME phenotype (88%), childhood absence epilepsy evolving into JME (6%), JME with adolescent absences (4%), and JME with astatic seizures (2%). More than a quarter (28%) had a family history of epilepsy. The most commonly used antiepileptic drug (AED) was sodium valproate in 78% of individuals, followed by levetiracetam (64%) and lamotrigine (55%). In the previous year, 47.5% were seizure-free. Using the International League against Epilepsy (ILAE) definitions and considering National Institute for Health and Care Excellence (NICE)-recommended AEDs for this syndrome, 121 individuals (50.4%) were identified as having refractory epilepsy. DISCUSSION: Juvenile myoclonic epilepsy is often regarded as a benign epileptic syndrome, but in this setting, half of the individuals with JME have refractory epilepsy with only about a quarter of those seizure-free in the previous year. Despite some advances in the understanding of this syndrome, there is still much to do before we can offer all the best outcomes.

Retention of perampanel in adults with pharmacoresistant epilepsy at a single tertiary care center.

RATIONALE: Observational data on antiepileptic drugs (AEDs) inform about their use in clinical practice. We describe our clinical experience with perampanel (PER) in a large UK tertiary epilepsy center. METHODS: Adults initiated on PER between October 2012 and March 2015 were followed until they discontinued PER or 10 September 2016. Data on epilepsy syndrome, duration, seizure types, concomitant and previous AED use, PER dosing, efficacy and side effects were recorded. Efficacy was categorized as temporary or ongoing (at last follow-up) seizure freedom, ≥50% seizure reduction, or other benefit (e.g. No convulsions or daytime seizures). These categories were mutually exclusive except for people with temporary seizure freedom. RESULTS: 391 received a PER prescription, five of whom never took it. No follow-up data were available for ten. 83% had focal epilepsy. People were prescribed PER in addition to 1-7 (Interquartile range [IQR] 2, 2, 3) AEDs and had previously used up to 18 (IQR 5, 7, 10) AEDs. Total exposure was 639patient/years. Retention rates were 60.4% at one year, 48.3% at two years, and 42.7% at three years. 19 (5%) people reported seizure free periods lasting at least six months. A ≥50% reduction in seizures lasting at least six months was reported by 76 people (20%), and marked improvement for ≥6months was seen in 52 (14%). Five (1%) were taken off other AEDs and continued on PER monotherapy for 4-27months. Seizures were aggravated in 57 (15%). Somatic side effects were reported by 197 (52%), mostly CNS. Mood changes, irritability or challenging behavior were reported by 137 (36%). PER was discontinued by 211 (56%) due to adverse effects (39%), inefficacy (26%), or both (35%). No idiosyncratic adverse events were seen. CONCLUSION: PER resulted in some benefit in 40% of those exposed. Adverse effects on mental health and on balance were common and should be discussed with people before initiating PER.

Somatic complications of epilepsy surgery over 25 years at a single center.

INTRODUCTION: Epilepsy surgery is an effective treatment for refractory focal epilepsy. Risks of surgery need to be considered when advising individuals of treatment options. We describe the frequency and nature of physical adverse events associated with epilepsy surgery in a single center. MATERIAL AND METHODS: We reviewed the prospectively maintained records of adults who underwent epilepsy surgery at our center between 1990 and 2014 to identify peri/postsurgical adverse events. These were categorized into neurological deficits and those related to surgery (e.g. wound infections). Neurological deficits were categorized as expected or unexpected and into transient (≤3 months) or persistent (>3 months), RESULTS: There were 911 procedures with no peri-operative deaths. Persistent neurological adverse events were seen following 157 (17.2%) procedures. The most common persistent expected complication was quadrantanopia after temporal lobe resections (72/764, 9.4%). Unexpected persistent neurological complications occurred in 20 procedures (2.2%) and included: quadrantanopia (6, 0.7%); hemianopia (2, 0.2%); hemi/mono-paresis/sensory loss (9, 1%); dysphasia (10, 1%); frontalis muscle weakness (2, 0.2%); and oculomotor weakness (1, 0.1%). 106 surgery related adverse events occurred in 83 procedures, with severe infections requiring bone-flap removal in 24 (2.6%) procedures and intracranial infections in 8 (0.9%). The risk of post-resective severe infection increased by 4 fold (OR 4.32, 95% CI 2.1-8.9, p<0.001) with use of subdural EEG monitoring prior to resection. In consequence, in August 2011 we introduced antibiotic coverage in all individuals undergoing intracranial monitoring. Also, after August 2011 there was greater use of Stereo-EEG (SEEG) than subdural (OR 9.0 CI 0.36-224.2, p=0.18ns). One complicated by severe infection. Other surgical complications included haematoma (0.3%), hydrocephalus (0.3%) and CSF leak (1.2%). None had permanent complications. CONCLUSIONS: Adverse event rates are similar to other series. Epilepsy surgery carries well defined surgical and neurological risks. The risks of somatic adverse events, in addition to neuropsychiatric and neuropsychological complications need to be made clear to individuals considering this treatment option.