Norwegian population-based study of effectiveness of vagus nerve stimulation in patients with developmental and epileptic encephalopathies.

OBJECTIVE: Evaluate the long-term efficacy of vagus nerve stimulation (VNS) in patients with developmental and epileptic encephalopathies (DEE) compared with epilepsy patients without intellectual disability (ID). METHODS: Long-term outcomes from a Norwegian VNS quality registry are reported in 105 patients with DEEs (Lennox-Gastaut syndrome [LGS] n = 62; Dravet n = 16; Rett n = 9; other syndromes n = 18) were compared with 212 epilepsy patients without ID, with median follow-up of 88 and 72 months, respectively. Total seizure reduction was evaluated at 6, 12, 24, 36, and 60 months. Effect on different seizure types was evaluated at baseline and last observation carried forward (LOCF). RESULTS: Median monthly seizure frequency at LOCF was reduced by 42.2% (p < 0.001) in patients with DEE and by 55.8% (p < 0.001) in patients without ID. In DEE patients, ≥50% seizure reduction at 6 and 24 months were 17.1% and 37.1%, respectively, and 33.5% and 48.6% for patients without ID. Seizure reduction ≥75% at 60 months occurred in 14.3% of DEE patients and 23.1% of patients without ID. Highest median reduction was for atonic seizures, most notably 64.6% for LGS patients. A better effect was seen at 2 years among DEE patients with unchanged medication compared with those with changed medication (54.5% vs. 35.6% responders, p = 0.078). More DEE patients were reported to have greater improvement in ictal or postictal severity (43.8% vs. 28.3%, p = 0.006) and alertness (62.9% vs. 31.6%, p < 0.001) than patients without ID. For both groups, use of the magnet reduced seizure severity. Hoarseness was the most common adverse effect in both groups. In addition, DEE patients were frequently reported to have sleep disturbance, general discomfort, or abdominal problems. SIGNIFICANCE: Our data indicate that VNS is very effective for atonic seizures. Patients without ID had best overall seizure reduction, however, patients with DEE had higher retention rates probably due to other positive effects. PLAIN LANGUAGE SUMMARY: DEE refers to a group of patients with severe epilepsy and intellectual disability. Many of these patients have restricted lifestyles with frequent seizures. VNS is a treatment option for patients who do not respond well to medicines, either because of insufficient effect or serious adverse effects. Our study shows that VNS is well tolerated in this patient group and leads to a reduction in all seizure types, most notably for seizures leading to fall. Many patients experience other positive effects like shorter and milder seizures, as well as improvement in alertness.

Temporal lobe epilepsy. / Temporallappsepilepsi.

The temporal lobes are the part of the brain most likely to give rise to epileptic seizures. Seizures originating in the temporal lobes vary greatly in character; some may be so unusual that they are not even recognised as epileptic. For patients who have been diagnosed with hippocampal sclerosis and whose seizures cannot be controlled with drugs, epilepsy surgery may be a good treatment option. In this brief clinical review, we summarise the key features of epilepsy and highlight the importance of accurate and early diagnosis for achieving good clinical outcomes.

Norwegian population-based study of long-term effects, safety, and predictors of response of vagus nerve stimulation treatment in drug-resistant epilepsy: The NORPulse study.

OBJECTIVE: This study was undertaken to evaluate the efficacy of vagus nerve stimulation (VNS) over time, and to determine which patient groups derive the most benefit. METHODS: Long-term outcomes are reported in 436 epilepsy patients from a VNS quality registry (52.8% adults, 47.2% children), with a median follow-up of 75 months. Patients were stratified according to evolution of response into constant responders, fluctuating responders, and nonresponders. The effect was evaluated at 6, 12, 24, 36, and 60 months. Multivariate regression analysis was used to identify predictors of response. RESULTS: The cumulative probability of ≥50% seizure reduction was 60%; however, 15% of patients showed a fluctuating course. Of those becoming responders, 89.5% (230/257) did so within 2 years. A steady increase in effect was observed among constant responders, with 48.7% (19/39) of those becoming seizure-free and 29.3% (39/133) with ≥75% seizure reduction achieving these effects within 2-5 years. Some effect (25%-<50%) at 6 months was a positive predictor of becoming a responder (odds ratio [OR] = 10.18, p < .0001) and having ≥75% reduction at 2 years (OR = 3.34, p = .03). Patients without intellectual disability had ORs of 3.34 and 3.11 of having ≥75% reduction at 2 and 5 years, respectively, and an OR of 6.22 of being seizure-free at last observation. Patients with unchanged antiseizure medication over the observation period showed better responder rates at 2 (63.0% vs. 43.1%, p = .002) and 5 years (63.4% vs. 46.3%, p = .031) than patients whose antiseizure medication was modified. Responder rates were higher for posttraumatic (70.6%, p = .048) and poststroke epilepsies (75.0%, p = .05) than other etiologies (46.5%). SIGNIFICANCE: Our data indicate that the effect of VNS increases over time and that there are important clinical decision points at 6 and 24 months for evaluating and adjusting the treatment. There should be better selection of candidates, as certain patient groups and epilepsy etiologies respond more favorably.

Rhythmic Midtemporal Discharge in a Youth During Light Sleep.

Rhythmic midtemporal discharge (RMTD) is a rare, benign EEG pattern that may have epileptic morphology. Recognizing variations of RMTD is important in order to avoid over- or misinterpretation of EEG findings, which may lead to inappropriate treatment and negative consequences for the patient in question. We present a case report of RTMDs during light sleep where initial erroneous description necessitated repeat EEGs and additional diagnostic exams and led to the postponement of obtaining a drivers licence for this young patient.

A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation.

PURPOSE: This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). METHODS: Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. RESULTS: Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials. CONCLUSIONS: The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients.

Aicardi syndrome: an epidemiologic and clinical study in Norway.

BACKGROUND: Aicardi syndrome is a rare neurodevelopmental disorder. The main diagnostic features are agenesis of corpus callosum, chorioretinal lacunae, and infantile spasms. The outcome is in general severe, with poor cognitive development and difficult-to-treat epilepsy. The aim of this study was to perform a nationwide epidemiologic survey of patients with Aicardi syndrome and describe their clinical features. Norway is a small country with a well-developed health system, making epidemiologic studies of rare diseases feasible and reliable. METHODS: We aimed at identifying all patients diagnosed with Aicardi syndrome in Norway. Prevalence of Aicardi syndrome was calculated for January 1, 2011. All available patients were examined, and their medical records were scrutinized. RESULTS: Six females aged 7 to 27 years with the diagnosis of Aicardi syndrome were identified. With a female population of 949,578 in ages 0 to 29 years, we found an age-adjusted prevalence of 0.63 per 100,000 females. One patient never had epileptic seizures. The other five had all experienced infantile spasms, all had at some point hypsarrhythmia in electroencephalography, two had a clear picture of suppression burst, whereas three had periods of suppression. Four of the five patients with seizure disorders experienced a marked improvement with time. CONCLUSION: We found an age-adjusted prevalence of 0.63 per 100,000 females with Aicardi syndrome and that their seizure disorder appeared to improve with age.

[Epilepsy surgery--assessment and patient selection]. / Epilepsikirurgi--utredning og pasientseleksjon.

BACKGROUND: Considerable progress in diagnostic imaging and video EEG monitoring has improved the possibilities of localising the epileptogenic zone of the brain in patients with epilepsy. Despite the fact that epilepsy surgery can therefore be offered to more patients today than previously, relatively few patients are referred for an assessment for surgery. The aim of this review is to provide a brief account of the patient selection procedures and the investigations prior to epilepsy surgery. METHOD: The review is based on a literature search in PubMed and the personal experiences of the authors in this field. RESULTS: If the epilepsy does not respond to any kind of pharmacological treatment, and idiopathic generalised epilepsy and pseudoresistance have been ruled out, the patient should be evaluated for surgery. The evaluation is multidisciplinary, and the aim is to localise the epileptogenic zone, which can be identified by both structural and functional abnormalities. It must be determined before the operation whether the zone can be removed without leaving severe neurological or cognitive impairment. The best results after epilepsy surgery are seen in patients with a morphological substrate, particularly temporal lobe epilepsy associated with hippocampal sclerosis. INTERPRETATION: Epilepsy surgery plays an ever more important role in the treatment of patients with drug resistant seizures. Doctors who treat epileptic patients should refer candidates for surgery at an early stage of the disease.

Efficacy and tolerability of long-term treatment with vagus nerve stimulation in adolescents and adults with refractory epilepsy and learning disabilities.

The long-term effects of vagus nerve stimulation (VNS) on seizure frequency were studied in 50 patients with epilepsy and learning disabilities. Mean observation time was 4.6 years. At follow-up, none of the patients was seizure-free, 25% had more than 50% seizure reduction, and 46% had some seizure reduction, but less than 50%. The discontinuation rate was 18%. Our results indicate that, like antiepileptic drugs, VNS does not have such a good seizure-reducing effect in patients with epilepsy and learning disabilities compared with the general epilepsy population.

Long-term vagus nerve stimulation in the treatment of Lennox-Gastaut syndrome.

The long-term effects of vagus nerve stimulation (VNS) on seizure frequency were studied in 30 patients with Lennox-Gastaut syndrome. Median observation time was 52 months (17-123). The effect parameters investigated were total number of seizures and different seizure types. The median reduction in number of seizures was 60.6%. The effects of VNS varied considerably between seizure types. Best effects were observed with atonic seizures (80.8% median reduction, number of responders: 8/12), followed closely by tonic seizures (73.3% median reduction, number of responders: 8/13). Least effects were with generalized tonic-clonic seizures (median reduction 57.4%, number of responders: 11/20). Additional positive effects included milder or shorter ictal or postictal phase in 16 patients. Improved alertness was reported in 76.7%. Adverse effects, of which drooling and voice alteration were most frequent, were reported in 20 patients. There was a statistically significant reduction in the median number of antiepileptic drugs used. The discontinuation rate was 16.7%.

[Epilepsia partialis continua (Kojevnikov's syndrome)]. / Epilepsia partialis continua (Kojevnikovs syndrom).

BACKGROUND: Lesions close to the central sulcus may give rise to focal motor seizures of long duration. This condition is called epilepsia partialis continua (Kojevnikov's syndrome). MATERIAL AND METHODS: Over the last two years, the National Centre for Epilepsy in Norway has treated 12 patients with epilepsia partialis continua. We discuss the occurrence, etiologies, semiology, findings from supplementary investigations, and therapeutic options on the basis of relevant literature and our own experience with these patients. RESULTS AND INTERPRETATION: Morphological lesions were found in 10 out of these 12 patients; cortical dysplasia in 3 patients, brain tumour in 2 patients, cerebral infarction in 2 patients, Rasmussen syndrome in 2 patients, and cerebral haemorrhage from an arteriovenous malformation in 1 patient. 9 patients had intermittent periods of jerking lasting from some hours to several days; the remaining 3 had permanent jerks. One of them had had this condition for 44 years. In 11 patients the jerks were localised to the face and/or the hand. The effect of antiepileptic drugs was disappointing; none became seizure-free. Five patients had undergone surgery. Surgical lesionectomy in this brain area is associated with a high risk of damage to eloquent cortex, but multiple subpial transections may have a seizure-blocking effect. One patient with Rasmussen's syndrome became seizure-free after a functional hemispherotomy.

A patient with a 44-year history of epilepsia partialis continua caused by a perirolandic cortical dysplasia.

Epilepsia partialis continua (EPC), or Kojevnikov's syndrome, is a rare epileptic syndrome arising from a variety of lesions in the perirolandic area. We report herein a 46-year-old woman with drug-resistant EPC due to a cortical dysplasia in the left frontoparietal region. For 44 years she has suffered continuous right-sided jerks, particularly in the right arm and hand, with an average frequency of 10-20 jerks per minute. During EEG recordings her jerks were associated with spikes and sharp waves over the left frontocentroparietal region, sometimes also with bursts of high-voltage generalized spike-wave complexes with a maximum bicentrally, followed by an electrodecrement. Despite the continuous jerks she is independent in daily life activities, and she considers the jerks not severe enough to justify surgery, i.e., multiple subpial transections.