Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

The long-term outcomes of patients with negative prolonged ambulatory electroencephalography tests: A cross-sectional follow-up study.

Background: Ambulatory electroencephalography (AEEG) recording is an essential aid for detecting interictal discharges and providing a clinical diagnosis. This study aimed to describe long-term outcomes among a cohort of patients who yielded negative results on AEEG at the time of assessment and identify factors associated with contemporary quality of life (QOL) and ultimate epilepsy diagnosis. Methods: This cross-sectional telephone follow-up study was conducted in June-November 2021 at the Neurology Department in a metropolitan hospital in Sydney, Australia. Results: In total, 47 of 105 eligible (45%) participants were enrolled. Overall, 21 (45%) participants had been diagnosed with epilepsy at a 12-year follow-up. Taking anti-seizure medication, having experienced a seizure event, and having marriage and education-related characteristics were associated with an epilepsy diagnosis. QOL was found to be associated with age, employment status and history of experience of a seizure event. QOL and an epilepsy diagnosis were not shown to be statistically related. Conclusions: Nearly half of the participants had received an epilepsy diagnosis at long-term follow-up, despite having tested negative on AEEG at the time of assessment. Prolonged AEEG testing is an important tool to aid the diagnostic process. However, clinical examination, including accurate history taking, is vital in establishing an epilepsy diagnosis.

Ambulatory electroencephalography (AEEG) recording is an essential aid for detecting interictal discharges and providing a clinical diagnosis. This study aimed to describe long-term outcomes among a cohort of patients who yielded negative results on AEEG at the time of assessment and identify factors associated with contemporary quality of life (QOL) and ultimate epilepsy diagnosis. This cross-sectional telephone follow-up study was conducted in June-November 2021 at the Neurology Department in a metropolitan hospital in Sydney, Australia. In total, 47 of 105 eligible (45%) participants were enrolled. Overall, 21 (45%) participants had been diagnosed with epilepsy at a 12-year follow-up. Taking anti-seizure medication, having experienced a seizure event, and having marriage and education-related characteristics were associated with an epilepsy diagnosis. QOL was found to be associated with age, employment status and history of experience of a seizure event. QOL and an epilepsy diagnosis were not shown to be statistically related. Nearly half of the participants had received an epilepsy diagnosis at long-term follow-up, despite having tested negative on AEEG at the time of assessment. Prolonged AEEG testing is an important tool to aid the diagnostic process. However, clinical examination, including accurate history taking, is vital in establishing an epilepsy diagnosis.

Vagus nerve stimulation for drug-resistant epilepsy.

Vagus nerve stimulation (VNS) is a neuromodulatory therapeutic option for drug-resistant epilepsy. In randomised controlled trials, VNS implantation has resulted in over 50% reduction in seizure frequency in 26%-40% of patients within 1 year. Long-term uncontrolled studies suggest better responses to VNS over time; however, the assessment of other potential predictive factors has led to contradictory results. Although initially designed for managing focal seizures, its use has been extended to other forms of drug-resistant epilepsy. In this review, we discuss the evidence supporting the use of VNS, its impact on seizure frequency and quality of life, and common adverse effects of this therapy. We also include practical guidance for the approach to and the management of patients with VNS in situ.

Seizures and epilepsy in the acute medical setting: presentation and management.

Epileptic seizures are a common cause for presentation to acute medical services. Whether presenting with an isolated, unprovoked seizure or with status epilepticus, a good understanding of seizures and their mimics ensures appropriate investigation and treatment. This article describes the practical aspects of the management of patients presenting with seizures to the emergency department or the acute medical unit.

The utility of prolonged outpatient ambulatory EEG.

PURPOSE: ILAE guidelines recommend the use of prolonged EEG where the diagnosis of epilepsy or the classification of the seizure syndrome is proving difficult. Due to its limited provision, video EEG monitoring is unavailable to many patients under investigation(1). The aim of this study was to examine the utility of the alternate investigation of outpatient ambulatory EEG. METHODS: In this retrospective study we analysed 324 consecutive prolonged outpatient ambulatory EEGs lasting 72-96 h (4-5 days), without medication withdrawal. EEG data and the clinical record were reviewed to investigate the utility of the investigation. RESULTS: Of 324 studies: 219 (68%) studies gave positive data, 116 (36%) showed interictal epileptiform discharges (IEDs), 167 (52%) had events. 105 (32%) studies were normal. Overall 51% of studies changed management of which 22% of studies changed the diagnosis and 29% of studies refined the diagnosis by classifying the epilepsy into focal or generalised. CONCLUSION: The present study confirms the diagnostic utility of outpatient ambulatory EEG in the diagnosis of paroxysmal events.

Latency to first interictal epileptiform discharge in epilepsy with outpatient ambulatory EEG.

OBJECTIVE: The diagnosis and classification of epilepsy often relies upon the demonstration of interictal epileptiform discharges (IEDs). Routine 20-min EEG recording has low sensitivity, with multiple EEGs increasing sensitivity to a maximum of 77% (Doppelbauer et al., 1993). An alternate strategy is the use of prolonged continuous EEG; however, there are no data on the average latency to first IED with ambulatory monitoring. METHODS: In this retrospective study we reviewed 180 consecutive patients with epilepsy referred to a Specialist Epilepsy Unit who had undergone 96 h outpatient ambulatory EEGs, without medication withdrawal, where IEDs were recorded. Latency to, and factors affecting first IED were analysed. RESULTS: Median latency to first IED was 316 min, (interquartile range 70-772 min, n=180). IEDs were recorded in 44% of patients within 4h, 58% within 8h, 85% within 24h and 95% within 48 h. Recording for the full 96 h period revealed only 5% further IEDs. Multivariate analysis showed the latencies to IEDs with generalised epilepsies were shorter than with focal epilepsies (p<0.0001). CONCLUSIONS: In 95% of patients showing scalp IEDs a 48 h recording was sufficient for electro-clinical classification in this study. SIGNIFICANCE: Our data are the first to show the latency to recording interictal epileptiform discharges with prolonged outpatient EEG monitoring. These data are important in guiding diagnostic practice in Specialist Epilepsy Services.

An electroclinical case-control study of sudden unexpected death in epilepsy.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) accounts for approximately 1 in 5 deaths in patients with epilepsy, but its cause remains unexplained. A recorded seizure resulting in death in our center appeared to suggest that postictal generalized electroencephalographic (EEG) suppression (PGES) and apnea are implicated in SUDEP. Our objective was to determine the association between PGES, as a possible identifiable EEG marker of profound postictal cerebral dysfunction, and SUDEP. METHODS: We studied 10 adult patients from our video-telemetry database who had 30 documented epileptic seizures during video-EEG recording and who later died of SUDEP. They were compared with 30 matching live controls with 92 epileptic seizures taken from the same database. Clinical and EEG findings were analyzed. RESULTS: PGES was seen in 15/30 (50%) case and 35/92 (38%) control seizures. A Mann-Whitney U test showed that PGES was significantly longer in the generalized motor seizures of the SUDEP group (p < 0.001). After adjustment for variables, odds ratio analysis of all seizures indicated significantly elevated odds of SUDEP with PGES durations of >50 seconds (p < 0.05). Beyond 80 seconds, the odds were quadrupled (p < 0.005). After adjustment for variables, for each 1-second increase in duration of PGES, the odds of SUDEP increased by a factor of 1.7%(p < 0.005). INTERPRETATION: Prolonged PGES (>50 seconds) appears to identify refractory epilepsy patients who are at risk of SUDEP. Risk of SUDEP may be increased in direct proportion to duration of PGES. Profound postictal cerebral dysfunction, possibly leading to central apnea, may be a pathogenetic mechanism for SUDEP.

Epilepsy surgery for refractory epilepsy due to encephalocele: a case report and review of the literature.

The management of medically intractable epilepsy is frequently assisted by the identification of structural abnormalities made possible by modern imaging techniques. The association between meningoencephaloceles and epileptic seizures is well reported in the literature. We report a patient with refractory right frontal lobe epilepsy caused by a right nasal meningoencephalocele who was rendered seizure free by endoscopic nasal excision and skull base repair, obviating the need for resective epilepsy surgery. Epilepsy patterns associated with encephalocele and their management are reviewed.