Vagus nerve stimulation in drug-resistant epilepsy: the efficacy and adverse effects in a 5-year follow-up study in Iran

Key pointsr On-demand optogenetic inhibition of glutamatergic neurons in the fastigial nucleus of the cerebellum does not alter hippocampal seizures in a mouse model of temporal lobe epilepsy.r In contrast, on-demand optogenetic excitation of glutamatergic neurons in the fastigial nucleus successfully inhibits hippocampal seizures. With this approach, even a single 50 ms pulse of light is able to significantly inhibit seizures.r On-demand optogenetic excitation of glutamatergic fastigial neurons either ipsilateral or contralateral to the seizure focus is able to inhibit seizures.r Selective excitation of glutamatergic nuclear neurons provides greater seizure inhibition than broadly exciting nuclear neurons without cell-type specificity.Abstract Temporal lobe epilepsy is the most common form of epilepsy in adults, but current treatment options provide limited efficacy, leaving as many as one-third of patients with uncontrolled seizures. Recently, attention has shifted towards more closed-loop therapies for seizure control, and on-demand optogenetic modulation of the cerebellar cortex was shown to be highly effective at attenuating hippocampal seizures. Intriguingly, both optogenetic excitation and inhibition of cerebellar cortical output neurons, Purkinje cells, attenuated seizures. The mechanisms by which the cerebellum impacts seizures, however, are unknown. In the present study, we targeted the immediate downstream projection of vermal Purkinje cells -the fastigial nucleus -in order to determine whether increases and/or decreases in fastigial output can underlie seizure cessation. Though Purkinje cell input to fastigial neurons is inhibitory, direct optogenetic inhibition of the fastigial nucleus had no effect on seizure duration. Conversely, however, fastigial excitation robustly attenuated hippocampal seizures. Seizure cessation was achieved at multiple stimulation frequencies, regardless of laterality relative to seizure focus, and even with single light pulses. Seizure inhibition was greater when selectively targeting glutamatergic fastigial neurons than when an approach that lacked cell-type specificity was used. Together, these results suggest Martha Streng received a BA in Neuroscience and Behaviour from Mount Holyoke College and a PhD in Neuroscience from the University of Minnesota, Twin Cities, where she studied the encoding of motor predictive and feedback information by Purkinje cells during online motor control tasks. Her current research focuses on the characterization of cerebellar circuitry and output channels in health and disease. that stimulating excitatory neurons in the fastigial nucleus may be a promising approach for therapeutic intervention in temporal lobe epilepsy.

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“…; Pakdaman et al . ). Targeting areas outside the seizure focus has shown some promise (Fisher et al .…”

Section: Introductionmentioning

confidence: 97%

Excitation, but not inhibition, of the fastigial nucleus provides powerful control over temporal lobe seizures

Streng

Krook-Magnuson

2019

The Journal of Physiology

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“…Cervical vagus nerve stimulation (VNS) is an FDA-approved treatment of drug-resistant epilepsy (Nune et al, 2015) and therapy-refractory major depression (Cristancho et al, 2011). The effectiveness of invasive cervical VNS in patients with drug-resistant epilepsy has been demonstrated repeatedly (Pakdaman et al, 2016;Kawai et al, 2017;Vivas et al, 2017). Furthermore, some initial trials on noninvasive transcutaneous auricular VNS reported promising results (He et al, 2013;Bauer et al, 2016;Barbella et al, 2018), although not all studies demonstrated effectiveness (Song et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Effect of vagus nerve stimulation on blood glucose concentration in epilepsy patients – Importance of stimulation parameters

et al. 2019

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In previous animal experiments, we demonstrated that cervical vagus nerve stimulation (VNS) inhibits pancreatic insulin secretion, thereby raises blood glucose levels, and impairs glucose tolerance through afferent signaling. However, there are no reports suggesting that similar effects occur in patients treated with chronic cervical VNS for epilepsy. In contrast to clinical VNS used for epilepsy, where the stimulation is intermittent with cycles of on and off periods, stimulation was continuous in our previous animal experiments. Thus, we hypothesized that the timing of the stimulation on/off cycles is critical to prevent impaired glucose tolerance in epilepsy patients chronically treated with cervical VNS. We conducted a retrospective analysis of medical records from patients with epilepsy. Blood glucose levels did not differ between patients treated with pharmacotherapy only (98 ± 4 mg/dL, n = 16) and patients treated with VNS plus pharmacotherapy (99 ± 3 mg/dL, n = 24, duration of VNS 4.5 ± 0.5 years). However, a multiple linear correlation analysis of patients with VNS demonstrated that during the follow‐up period of 7.9 ± 0.7 years, blood glucose levels increased in patients with long on and short off periods, whereas blood glucose did not change or even decreased in patients that were stimulated with short on and long off periods. We conclude that chronic cervical VNS in patients with epilepsy is unlikely to induce glucose intolerance or hyperglycemia with commonly used stimulation parameters. However, stimulation on times of longer than 25 sec may bear a risk for hyperglycemia, especially if the stimulation off time is shorter than 200 sec.

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“…These results appear better for temporal lobe surgeries. Table 4 shows neurostimulative techniques like VNS [57,86,120,138,151,157,173] and deep brain stimulation [73], which reflected that the majority of subjects had more than 50% seizure reduction with follow-ups ranging between one to four years. Table 5 showed that the indicators of QOL improved after surgery [37,47,50,59,93,98,101,122,126,134,159,160,165,175,177], except in one study [62].…”

Section: Tunisian Epilepsy Surgery Program At the Charles Nicolle Hosmentioning

confidence: 99%

Epilepsy surgery in low- and middle-income countries: A scoping review

Watila

Xiao

Keezer

et al. 2019

Epilepsy & Behavior

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Background: Epilepsy surgery is an important treatment option for people with drug resistant epilepsy. Although surgical procedures are under-utilized worldwide, it is far worse in Low-and Middle-Income Countries (LMIC) and it is less clear to what extent people with drug resistant epilepsy receive such treatment at all. Here we review the existing evidence for the availability and outcome of epilepsy surgery in LMIC, and discuss some challenges and priority. Methods: We used the six stage methodological framework developed by Arskey and O'Malley as a guide. We searched PubMed, Embase, Global Health Archives, Index Medicus for South East Asia Region (IMSEAR), Index Medicus for Eastern Mediterranean Region (IMEMR), Latin American & Caribbean Health Sciences Literature (LILACS), African Journal Online (AJOL), and African Index Medicus (AIM) to identify the relevant literature. Results: We retrieved 148 articles on epilepsy surgery from 31 countries representing 22% of the 143 LMIC. Epilepsy surgery appears established in some of these centers in Asia and Latin America, while some are in their embryonic stage reporting procedures in a small cohort performed mostly by motivated neurosurgeons. The commonest surgical procedure reported was temporal lobectomies. The post-operative seizure-free rates and quality of life are comparable to those in the high-income countries (HIC). Some models have shown that epilepsy surgery can be performed within a resourcelimited setting through collaboration with international partners and through the use of information and communication technology. The cost of surgery is a fraction of what is available in HIC. Conclusion: This review has demonstrated the availability of epilepsy surgery in few LMIC. The information available is inadequate to make any reasonable conclusion of its existence as routine practice. Collaborations with international partners can provide an opportunity to bring high-quality academic training and technological transfer directly to surgeons working in these regions and should be encouraged.

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Vagus nerve stimulation in drug-resistant epilepsy: the efficacy and adverse effects in a 5-year follow-up study in Iran

Cited by 20 publications

References 30 publications

Excitation, but not inhibition, of the fastigial nucleus provides powerful control over temporal lobe seizures

Excitation, but not inhibition, of the fastigial nucleus provides powerful control over temporal lobe seizures

Effect of vagus nerve stimulation on blood glucose concentration in epilepsy patients – Importance of stimulation parameters

Epilepsy surgery in low- and middle-income countries: A scoping review

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