Vagus nerve stimulation treatment for Lennox-Gastaut syndrome

Lennox-Gastaut syndrome is a severe age-specific epilepsy syndrome that presents with medication-resistant seizures in childhood. Antiepileptic drugs are the mainstay of treatment. Nonpharmacologic treatments include corpus callosum section and the ketogenic diet. However, no single treatment is safe and effective. We treated 13 patients with Lennox-Gastaut syndrome between the ages of 4 and 44 years (mean, 16.7 years) with vagus nerve stimulation. During the first 6 months of treatment, vagus nerve stimulation produced a median seizure rate reduction of 52% (range, 0% to 93%; P = .04). At 6 months of follow-up, three patients had a greater than 90% reduction in seizures, two had a greater than 75% reduction, one had a greater than 50% reduction, and six had at least a 25% reduction. One patient did not improve. No patient worsened after initial improvement. Side effects, including hoarseness, coughing, and pain in the throat, were transient and tolerable. No patient discontinued vagus nerve stimulation. Our results suggest that vagus nerve stimulation could be an effective and safe adjunct therapy for the treatment of Lennox-Gastaut syndrome.     

Vagus nerve stimulation for the treatment of intractable epilepsy

Vagus nerve stimulation is a safe and reliable treatment adjunct for patients with medically intractable epilepsy. It is both a preventive and abortive form of therapy, potentially effective against both partial and generalized seizures in adults and children. Vagus nerve stimulation also has a number of serendipitous effects on mood, memory and attention, and has been approved for the treatment of refractory depression. Owing to its pleiotropic effects, it also holds promise for several other diseases. Its principal limitations are its unknown mechanism of action, the low likelihood of complete cure and the inability to predict which patients will derive substantial benefit. This article reviews the theoretical rationale, practical background and clinical applications of vagus nerve stimulation therapy.     

Vagus nerve stimulation in the treatment of refractory epilepsy

Many patients with epilepsy suffer from persistent seizures despite maximal anti-epileptic drug therapy. Chronic, intermittent vagus nerve stimulation has been proven to be an effective option for many patients suffering from refractory seizures who are not candidates for surgical resection. Although only a small minority of patients will be entirely seizure-free, vagus nerve stimulation, as an adjunct to medical therapy, may result in significant improvements in quality of life. Vagus nerve stimulation is generally well-tolerated, as device implantation is associated with a low rate of perioperative complications, and the majority of side effects are stimulation-dependent and thus reversible.     

Vagus nerve stimulation for refractory epilepsy.

Vagus nerve stimulation (VNS) is a neurophysiological treatment for patients with medically or surgically refractory epilepsy. Since the first human implant in 1989, more than 10 000 patients have been treated with VNS. Two randomized controlled studies have shown a statistically significant decrease in seizure frequency during a 12-week treatment period versus a baseline period when 'high stimulation' mode was compared with 'low stimulation' mode. The efficacy appears to increase over time. In general, one third of the patients show a >50% reduction of seizure frequency; one third show a 30-50% seizure reduction, and one third of patients show no response. Few patients become seizure-free. Side effects during stimulation are mainly voice alteration, coughing, throat paraesthesia and discomfort. When studied on a long-term basis, VNS is an efficacious, safe and cost-effective treatment not only in adults but also in children and the elderly. The precise mechanism of action remains to be elucidated. In recent years much progress has been made through neurophysiological, neuroanatomical, neurochemical and cerebral blood flow studies in animals and patients treated with VNS. Further elucidation of the mechanism of action of VNS may increase its clinical efficacy and our general understanding of some physiopathological aspects of epilepsy. Finally, VNS may become an alternative treatment for other conditions such as depression and pain.     

迷走神经刺激术-程控电刺激治疗难治性癫痫

目的 应用迷走神经刺激术(vagus nerve stimulation,VNS)治疗难治性癫痫,并探讨其治疗机制和方法。方法 个体化的VNS疗效预测和精确无误的VNS植入,适时恰当的刺激参数程控调校,并以长程脑电图、SPECT观测VNS带来的脑功能改变。结果 接受VNS术3个月后,3例病患的发作频次均减少50％以上,2例在应急磁铁的辅助下基本不再表现复杂性发作,1例不再表现全身失张性发作,而以部分性发作为主,偶有复杂发作,生活质量提高。脑电图原有的棘波、尖波消失或减少,阵发性异常消失或时间缩短。发作间期SPECT表现为原有的低代谢灶缩小。结论 恰当地应用VNS能够为难治性癫痫提供一种有效、微创、副作用极少的治疗手段。     

Vagus nerve stimulation for medically refractory absence epilepsy

PurposeA proportion of patients with childhood and juvenile absence epilepsies (CAE, JAE) are likely to be classified as medically refractory. In view of evidence gap for the treatment of such patients, this series is reported to generate estimate for efficacy of vagus nerve stimulation (VNS) in this patient population.MethodsPatients were identified by a chart review of all VNS recipients between January 1, 2006 and December 31, 2011. The diagnosis of CAE and JAE was based on conventional criteria. Details of demography, epilepsy phenomenology, management and outcomes were extracted. The outcome measures included reduction in daily seizure frequency measured as a percentage of pre-VNS seizure frequency and classified on International League Against Epilepsy (ILAE) outcome scale.ResultsNine patients (7 CAE, 2 JAE) with a mean age of seizure onset of 5.4 years (±3.9) were identified. Mean duration of epilepsy prior to VNS implant was found to be 3.9 years (±1.4). These patients had failed a median of 5 anti-epileptic drugs before being referred for consideration of surgical treatment. After a mean follow-up of 33.9 months (±25.5, minimum 4 months), 1 patient attained complete seizure freedom (ILAE class 1), 6 had ILAE class 4 and 2 had ILAE class 5 outcomes, respectively. Mean reduction in daily seizure frequency was found to be 53.5 ± 60.3% (1-sided p-value for paired t-test = 0.04), with a 50% responder rate of 55.6%.ConclusionVNS may be considered as a therapeutic option in patients with medically refractory absence epilepsy.     

Vagus nerve stimulation therapy for epilepsy in older adults

The authors assessed the efficacy, safety, and tolerability of vagus nerve stimulation (VNS) for refractory epilepsy in 45 adults 50 years of age and older. They determined seizure frequency, adverse effects, and quality of life. At 3 months, 12 patients had a >50% decrease in seizure frequency; at 1 year, 21 of 31 studied individuals had a >50% seizure decrease. Side effects were mild and transient. Quality of life scores improved significantly with time.     

Vagus nerve stimulation for the treatment of bilateral independent temporal lobe epilepsy

PURPOSE: We studied the effect of vagus nerve stimulation (VNS) on seizure reduction in patients with intractable epilepsy with bilateral independent temporal lobe foci. METHODS: Ten patients who met the criterion of the presence of two distinctive clinical and ictal EEG seizure patterns were identified and followed up for 1 year. RESULTS: Six patients had >50% reduction in their seizure frequency that persisted up to > or =1 year of follow-up, whereas four patients reported small or no reduction in their partial seizures. CONCLUSIONS: VNS is often effective and well tolerated in this select group of intractable epilepsy patients.     

Vagus nerve stimulation for refractory idiopathic generalised epilepsy.

We reviewed our experience with vagus nerve stimulation (VNS) in 165 patients with medically refractory epilepsy (138 partial epilepsy (PE), 13 symptomatic generalised epilepsy (SGE), 14 idiopathic generalised epilepsy (IGE)). Average duration of VNS therapy was 21.6 months. A 50% or greater reduction in seizure frequency was achieved in 47.1% of the PE group, 46.1% of the SGE group, and 57.1% of the IGE group. A 50% or greater reduction in seizure frequency and reduced antiepileptic drug (AED) regimen were achieved in: PE (9.4%), SGE (7.7%), and IGE (35.7%). These preliminary results suggest that VNS is an effective therapy for some patients with medically refractory IGE.     

Vagus nerve stimulation for epilepsy: a review.

Vagus nerve stimulation is an empirically based method for treatment of epilepsy by repeated stimulation of the left vagus nerve through implanted electrodes. Despite studies in animals and man, which show changes in brain electrophysiology, metabolism and neurochemistry, the mode of action remains unknown. Clinical testing has presented methodological challenges, as it is difficult to assess under double blind conditions a treatment which requires surgery and produces a sensation every time the stimulator comes on. This has nevertheless been successfully addressed in parallel design, controlled trials comparing high and low stimulation schedules. These have been performed in adults with medically intractable partial seizures, and demonstrated efficacy, safety and good tolerability. Efficacy, both in the controlled trials and in numerous reports arising from the considerable post-marketing experience is modest. Some 30% of patients achieve a 50% seizure reduction after 3 months of treatment, but this proportion progressively increases to about 50% after 18 months. Side-effects comprise: discomfort in the face or neck when the stimulator is activated, coughing, breathlessness on exertion and hoarseness of voice. All are related to intensity of stimulation and rapidly habituate in most subjects. In those patients who respond, a stimulus level can therefore generally be found which is acceptable to the subject. No indication other than refractory partial seizures in adults has been the subject of controlled trials, but post-marketing experience and uncontrolled reports indicate comparable efficacy and safety in a wide range of epilepsies, partial and generalized, idiopathic, cryptogenic, or symptomatic, in patients of all ages.     

Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms

Vagus nerve stimulation (VNS) is an effective adjunctive treatment for intractable epilepsy. However, the optimal range of device duty-cycles [on/(on + off times)] is poorly understood. The authors performed a multicenter, randomized trial of three unique modes of VNS, which varied primarily by duty-cycle. The results indicate that the three duty-cycles were equally effective. The data support the use of standard duty-cycles as initial therapy.     

Vagus nerve stimulation paired with tones restores auditory processing in a rat model of Rett syndrome

BackgroundRett syndrome is a rare neurological disorder associated with a mutation in the X-linked gene MECP2. This disorder mainly affects females, who typically have seemingly normal early development followed by a regression of acquired skills. The rodent Mecp2 model exhibits many of the classic neural abnormalities and behavioral deficits observed in individuals with Rett syndrome. Similar to individuals with Rett syndrome, both auditory discrimination ability and auditory cortical responses are impaired in heterozygous Mecp2 rats. The development of therapies that can enhance plasticity in auditory networks and improve auditory processing has the potential to impact the lives of individuals with Rett syndrome. Evidence suggests that precisely timed vagus nerve stimulation (VNS) paired with sound presentation can drive robust neuroplasticity in auditory networks and enhance the benefits of auditory therapy.ObjectiveThe aim of this study was to investigate the ability of VNS paired with tones to restore auditory processing in Mecp2 transgenic rats.MethodsSeventeen female heterozygous Mecp2 rats and 8 female wild-type (WT) littermates were used in this study. The rats were exposed to multiple tone frequencies paired with VNS 300 times per day for 20 days. Auditory cortex responses were then examined following VNS-tone pairing therapy or no therapy.ResultsOur results indicate that Mecp2 mutation alters auditory cortex responses to sounds compared to WT controls. VNS-tone pairing in Mecp2 rats improves the cortical response strength to both tones and speech sounds compared to untreated Mecp2 rats. Additionally, VNS-tone pairing increased the information contained in the neural response that can be used to discriminate between different consonant sounds.ConclusionThese results demonstrate that VNS-sound pairing may represent a strategy to enhance auditory function in individuals with Rett syndrome.     

Vagus nerve stimulation in pediatric epilepsy: a review

Therapeutic options for intractable epilepsy include new and investigational antiepileptic drugs, ketogenic diet, epilepsy surgery, and, now, vagus nerve stimulation, which is approved by the U.S. Food and Drug Administration for the treatment of refractory partial seizures in adolescents and adults. The exact mechanisms of action are unknown. Although the use of vagus nerve stimulation in children has increased, including those younger than 12 years of age or those with generalized epilepsy, there has been no large controlled pediatric study to date. The identification of favorable prognostic indicators, especially in children, would be useful. Preliminary results suggest that children with Lennox-Gastaut syndrome may have a favorable response, with improvement in both seizure control and global evaluation scores. Improved global evaluation scores have occurred even without an associated improvement in seizure control.     

Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients

BACKGROUND: Given that vagal afferents project to brainstem regions that promote alertness, the authors tested the hypothesis that vagus nerve stimulation (VNS) would improve daytime sleepiness in patients with epilepsy. METHODS: Sixteen subjects with medically refractory seizures underwent polysomnography and multiple sleep latency tests (MSLT) and completed the Epworth Sleepiness Scale (ESS), a measure of subjective daytime sleepiness, before and after 3 months of VNS. Most subjects (>80%) were maintained on constant doses of antiepileptic medications. RESULTS: In the 15 subjects who completed baseline and treatment MSLT, the mean sleep latency (MSL) improved from 6.4 +/- 4.1 minutes to 9.8 +/- 5.8 minutes (+/- SD; p = 0.033), indicating reduced daytime sleepiness. All subjects with stimulus intensities of < or =1.5 mA showed improved MSL. In the 16 subjects who completed baseline and treatment ESS, the mean ESS score decreased from 7.2 +/- 4.4 to 5.6 +/- 4.5 points (p = 0.049). Improvements in MSLT and ESS were not correlated with reduction in seizure frequency. Sleep-onset REM periods occurred more frequently in treatment naps as compared to baseline naps (p < 0.008; Cochran-Mantel-Haenszel test). The amount of REM sleep or other sleep stages recorded on overnight polysomnography did not change with VNS treatment. CONCLUSIONS: Treatment with VNS at low stimulus intensities improves daytime sleepiness, even in subjects without reductions in seizure frequency. Daytime REM sleep is enhanced with VNS. These findings support the role of VNS in activating cholinergic and other brain regions that promote alertness.