Pre-ictal heart rate variability alterations in focal onset seizures and response to vagus nerve stimulation.

PURPOSE: Vagus nerve stimulation (VNS) is an effective and well-known treatment for drug resistant epilepsy (DRE) patients since 1997, yet prediction of treatment response before implantation is subject of ongoing research. Neuroimaging and neurophysiological studies investigating the vagal afferent network in resting state documented that differences in between epilepsy patients were related to treatment response. This study investigated whether an event-related parameter, pre-ictal heart rate variability (HRV) is associated with response to VNS therapy. METHODS: DRE patients underwent video-electroencephalography (EEG) recording before VNS implantation. HRV parameters (time, non-linear and frequency domain) were assessed for every seizure during two 10 min timeframes: baseline (60 min before seizure onset) and pre-ictal (10 min before seizure onset). Pre-ictal HRV parameter alterations were correlated with VNS response after one year of VNS therapy and seizure characteristics (temporal/extratemporal, left/right or bilateral). RESULTS: 104 seizures from 22 patients were evaluated. Eleven patients were VNS responders with a seizure frequency reduction of ≥ 50 % after one year of VNS. In VNS responders no changes in HRV parameters were found while in VNS non-responders the time domain and non-linear HRV variables decreased significantly (p = 0.024, p = 0.005, p = 0.005) during the pre-ictal time frame. 10/11 VNS non-responders had a seizure lateralization to the left compared to 4/11 VNS responders. CONCLUSION: VNS non-responders were characterized by a significant decrease of pre-ictal HRV (time domain/non-linear variables) suggesting a sudden autonomic imbalance probably due to an impaired central autonomic function that makes it at the same time unlikely to respond to VNS.

A decade of experience with deep brain stimulation for patients with refractory medial temporal lobe epilepsy.

In this study, we present long-term results from patients with medial temporal lobe (MTL) epilepsy treated with deep brain stimulation (DBS). Since 2001, 11 patients (8M) with refractory MTL epilepsy underwent MTL DBS. When unilateral DBS failed to decrease seizures by > 90%, a switch to bilateral MTL DBS was proposed. After a mean follow-up of 8.5 years (range: 67-120 months), 6/11 patients had a ≥ 90% seizure frequency reduction with 3/6 seizure-free for > 3 years; three patients had a 40%-70% reduction and two had a < 30% reduction. In 3/5 patients switching to bilateral DBS further improved outcome. Uni- or bilateral MTL DBS did not affect neuropsychological functioning. This open study with an extended long-term follow-up demonstrates maintained efficacy of DBS for MTL epilepsy. In more than half of the patients, a seizure frequency reduction of at least 90% was reached. Bilateral MTL DBS may herald superior efficacy in unilateral MTL epilepsy.

Predictive factors for outcome of invasive video-EEG monitoring and subsequent resective surgery in patients with refractory epilepsy.

OBJECTIVE: This is a descriptive study of patients who underwent invasive video-EEG monitoring (IVEM) at Ghent University Hospital. The aim of the study is to identify predictive factors for outcome of IVEM and resective surgery (RS). These factors may optimize the patient flow following the non-invasive presurgical evaluation towards IVEM and RS or other treatments. PATIENTS AND METHODS: Over the past 16 years, 68/710 refractory epilepsy patients included in the presurgical evaluation protocol (M/F 41/27, mean age 33 years) underwent IVEM at Ghent University Hospital. Patient features and follow-up data were collected from the patients' medical files and the electronic patient database at the neurology and neurosurgery department. Predictive factors for IVEM outcome were identified by comparing features of patients with a positive IVEM outcome (i.e. ictal onset zone identification) and patients with a negative IVEM outcome. Predictive factors for RS outcome were identified by comparing features of patients with Engel class I and patients with Engel class II-IV outcome. RESULTS: In 56/68 patients (82%) IVEM outcome was positive. The occurrence of a seizure-free interval in the patient's history and a non-localizing ictal scalp EEG in patients with a structural abnormality on MRI (p<0.05) were predictive factors for a negative IVEM outcome. 32/68 patients underwent RS. In 22/32 (70%) patients RS resulted in an Engel class I outcome. A structural abnormality on MRI was a predictive factor for a positive RS outcome in patients in whom a focal or regional focus was resected (p<0.05). CONCLUSION: This study shows that IVEM identifies one or more ictal onset zone(s) in up to 80% of patients. The potential of IVEM to identify the ictal onset zone is unlikely in patients with a seizure-free interval in their medical history and a non-localizing ictal scalp EEG during the non-invasive presurgical evaluation. Half of these patients underwent RS with long-term seizure freedom in 70%. Patients with structural MRI lesions have the highest chance of seizure freedom. These findings may contribute to the optimization of patient management during both the invasive and non-invasive presurgical work-up.

A pilot trial with modified Atkins' diet in adult patients with refractory epilepsy.

OBJECTIVES: At Ghent University Hospital, the feasibility and efficacy of the modified Atkins' diet was evaluated in adult patients with refractory epilepsy. The Atkins' diet restricts carbohydrate intake and was originally designed for weight loss. PATIENTS AND METHODS: During a 6-month trial period, a carbohydrate restriction of 20 g/day was in place. During a 36 h hospital admission, patients were instructed about the diet. Patients underwent clinical neurological testing, EEG, ECG, blood and urine analyses and mood evaluation before and during the trial. Seizure frequency and side effects were recorded in seizure diaries and followed up at monthly clinic visits. RESULTS: Eight patients were included in the study. Three out of eight patients followed the diet for 6 months. One out of three patients showed a >50% seizure reduction, 1/3>30%, and 1/3<30%. Side effects such as constipation and diarrhoea were mild and occurred mainly during the initial week of the diet. Patients reported improved concentration and well being. This was confirmed by improved scores on the Beck Depression Inventory Scale. CONCLUSION: This pilot study shows that the modified Atkins' diet is feasible in an adult population, and that seizure frequency reduction is possible. The results need to be confirmed in larger prospective, controlled studies with comparison groups.

Deep brain stimulation in patients with refractory temporal lobe epilepsy.

PURPOSE: This pilot study prospectively evaluated the efficacy of long-term deep brain stimulation (DBS) in medial temporal lobe (MTL) structures in patients with MTL epilepsy. METHODS: Twelve consecutive patients with refractory MTL epilepsy were included in this study. The protocol included invasive video-EEG monitoring for ictal-onset localization and evaluation for subsequent stimulation of the ictal-onset zone. Side effects and changes in seizure frequency were carefully monitored. RESULTS: Ten of 12 patients underwent long-term MTL DBS. Two of 12 patients underwent selective amygdalohippocampectomy. After mean follow-up of 31 months (range, 12-52 months), one of 10 stimulated patients are seizure free (>1 year), one of 10 patients had a >90% reduction in seizure frequency; five of 10 patients had a seizure-frequency reduction of > or =50%; two of 10 patients had a seizure-frequency reduction of 30-49%; and one of 10 patients was a nonresponder. None of the patients reported side effects. In one patient, MRI showed asymptomatic intracranial hemorrhages along the trajectory of the DBS electrodes. None of the patients showed changes in clinical neurological testing. Patients who underwent selective amygdalohippocampectomy are seizure-free (>1 year), AEDs are unchanged, and no side effects have occurred. CONCLUSIONS: This open pilot study demonstrates the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multicenter randomized controlled trials.

Vagus nerve stimulation for refractory epilepsy: a transatlantic experience.

Vagus nerve stimulation (VNS) is an alternative treatment for medically or surgically refractory epilepsy. The long-term efficacy and safety of VNS were evaluated in a large patient series at Ghent University Hospital and Dartmouth-Hitchcock Medical Center. Between March 1995 and February 2003, seizure frequency and type as well as prescribed antiepileptic drugs and side effects were prospectively assessed in 131 patients treated with VNS in either center. Patients with a minimum follow-up duration of 6 months were included in the efficacy and safety analysis. A total of 118 of 131 implanted patients had a minimum postimplantation follow-up period of 6 months (mean, 33 months). The mean age of these patients was 32 years and the mean duration of refractory epilepsy was 22 years. The mean reduction in monthly seizure frequency in all patients was 55% (range, 0-100; SD = 31.6). Seven percent of patients were free of seizures with impaired consciousness, 50% of patients had a seizure frequency reduction of more than 50%, and 21% of patients were nonresponders. Fifteen patients reported stimulation-related side effects such as hoarseness or gagging. In a large patient series from two geographically distinct epilepsy centers located in two different continents, VNS proved to be efficacious and safe during long-term follow-up.

Neurostimulation for refractory epilepsy.

Neurostimulation is an emerging treatment for refractory epilepsy. To date the precise mechanism of action remains to be elucidated. Better insight in the mechanism of action may identify seizure types or syndromes that respond to such a treatment and may guide the search for optimal stimulation parameters and finally improve clinical efficacy. In the past ten years some progress has been made through neurophysiological, neuroanatomical, neurochemical and cerebral blood flow studies in patients and animals undergoing vagus nerve stimulation (VNS). Interesting results have been found in VNS-treated patients that underwent evoked potential measurements, cerebrospinal fluid investigation, neuropsychological testing and PET, SPECT and fMRI testing. Desynchronisation of abnormal synchronous epileptic activity is one of the hypotheses on the mode of action that might primarily be responsible for an anti-seizure effect. There is however increasing evidence from research and clinical observation that VNS might establish a true and long-term anti-epileptic effect. It has been shown that VNS influences neurotransmission in the brain and provokes long-term changes in cerebral blood flow in areas crucial for epileptogenesis such as the thalamus and medial temporal lobe structures. Deep brain stimulation (DBS) for epilepsy has regained interest. Central nervous system structures known to play a key role in the epileptogenic network such as the thalamus and subthalamic nucleus have been targeted. Another approach is to target the ictal onset zone such as the medial temporal lobe. At Ghent University Hospital 10 patients have been treated with long-term amygdalohippocampal DBS. Several hypotheses have been raised for the mechanism of action of DBS for refractory seizures. Seizure reduction may be due to a microlesion caused by electrode insertion or by provoking a reversible functional lesion due to the effect of electrical current on hyperexcitable tissue. Neurophysiological techniques such as evoked potentials monitoring and intraoperative single unit potential recordings may guide correct electrode placement, individual DBS titration and elucidation of the mechanims of action of DBS for epilepsy.