Vagus nerve stimulation for drug-resistant epilepsy

Vagus nerve stimulation for drug-resistant epilepsy

see also Responsive neurostimulation.


Vagus nerve stimulation for drug-resistant epilepsy was first approved in Europe in 1994 and in the United States (US) in 1997. Subsequent modifications improved the safety and the efficacy of the system. The most recent application of vagal neurostimulation is represented by transcutaneous devices that are claimed to have strong therapeutic potential. In a review, Toffa et al. sought to analyze the most meaningful available data describing the indications, safety and efficacy of the different approaches of VNS in clinical practice. Therefore, they identified studies reporting VNS efficacy and/or safety in epilepsy and its comorbidities from January 1990 to February 2020 from various databases including PubMed, Scopus, Cochrane, US government databases and VNS manufacturer published resources. In general, VNS efficacy becomes optimal around the sixth month of treatment and a 50-100 % seizure frequency reduction is achieved in approximately 45-65 % of the patients. However, some clinically relevant differences have been reported with specific factors such as epilepsy etiology or epilepsy classification, patient age as well as the delay of VNS therapy onset. VNS efficacy on seizure frequency has been demonstrated in both children and adults, in lesional and non-lesional cases, in focal and generalized epilepsies, on both seizures and epilepsy comorbidities. Regarding the latter, VNS can lead to an improvement of about 25-35 % in depression scores, 35 % in anxiety scores and 25 % in mood assessment scores. If non-invasive devices are undeniably safer, their efficacy is limited due to the scarcity of large cohort studies and the disparity of methodological approaches (study design and stimulation parameters). Overall, they believe that there is a progress margin for improving the safety of implantable devices and, above all, the effectiveness of the various VNS approaches 1).

see also Vagus nerve stimulation for drug-resistant epilepsy in children

VNS is indicated for symptomatic localization-related epilepsy with multiple and bilateral independent foci, symptomatic generalized epilepsy with diffuse epileptogenic abnormalities, refractory idiopathic generalized epilepsy, failed intracranial epilepsy surgery, and other several reasons of contraindications to epilepsy surgery. Programing of the parameters is a principal part in VNS. Output current and duty cycle should be adjusted to higher settings particularly when a patient does not respond to the initial setting, since the pivotal randomized trials performed in the United States demonstrated high stimulation made better responses in seizure frequency. These trials revealed that a ≥ 50% seizure reduction occurred in 36.8% of patients at 1 year, in 43.2% at 2 years, and in 42.7% at 3 years in 440 patients. Safety of VNS was also confirmed because side effects including hoarseness, throat discomfort, cough, paresthesia, and headache improved progressively during the period of 3 years. The largest retrospective study with 436 patients demonstrated the mean seizure reduction of 55.8% in nearly 5 years, and also found 75.5% at 10 years in 65 consecutive patients. The intermediate analysis report of the Japan VNS Registry showed that 60% of 164 cases got a ≥ 50% seizure reduction in 12 months. In addition to seizure reduction, VNS has positive effects in mood and improves energy level, memory difficulties, social aspects, and fear of seizures. VNS is an effective and safe option for patients who are not suitable candidates for intracranial epilepsy surgery 2).


Vagus nerve stimulation (VNS) is becoming an increasingly popular therapy for patients with drug resistant epilepsy 3) 4) 5) 6) 7) 8) 9) 10).

The use of functional neuroimaging such as SPECT, PET and fMRI in patients undergoing peripheral nerve stimulation can help us to understand these mechanisms.

Bari et al., reviewed the literature for functional neuroimaging performed in patients implanted with peripheral nerve stimulators. These studies suggest that brain activity in response to peripheral nerve stimulation is a complex interaction between the stimulation parameters, disease type and severity, chronicity of stimulation, as well as nonspecific effects. From this information we may be able to understand which brain structures are involved in the mechanism of peripheral nerve stimulation as well as define the neural substrates underlying these disorders 11).

Connor et al., performed a review of available literature published between 1980 and 2010. Inclusion criteria for articles included more than 10 patients evaluated, average follow-up of 1 or more years, inclusion of medically refractory epilepsy, and consistent preoperative surgical evaluation. Articles were divided into 4 classes of evidence according to criteria established by the American Academy of Neurology.

A total of 70 publications were reviewed, of which 20 were selected for review based on inclusion and exclusion criteria. There were 2 articles that provided Class I evidence, 7 that met criteria for Class II evidence, and 11 that provided Class III evidence. The majority of evidence supports VNS usage in partial epilepsy with a seizure reduction of 50% or more in the majority of cases and freedom from seizure in 6%-27% of patients who responded to stimulation. High stimulation with a gradual increase in VNS stimulation over the first 6 weeks to 3 months postoperatively is well supported by Class I and II data. Predictors of positive response included absence of bilateral interictal epileptiform activity and cortical malformations.

Vagal nerve stimulation is a safe and effective alternative for adult and pediatric populations with epilepsy refractory to medical and other surgical management 12).


A study looked at the research available on the effectiveness, safety, and cost of two types of electrical stimulation devices currently licensed for treatment of epilepsy for adults and children in Canada: vagus nerve stimulation (VNS) and deep brain stimulation (DBS). Both approaches appear to be effective at reducing the frequency of seizures in adults. However, the evidence on DBS is limited to a single study with adults; Chambers and Bowen found no studies of DBS with children. Studies on VNS showed that both adults and children had fewer hospitalizations and emergency department visits after the procedure. Both procedures carry serious risks, but several longer-term studies have found that adverse events appear to be limited. The cost of VNS, including the process of assessing whether or not patients are good candidates for the procedure, is estimated to be about $40,000 per person (and higher for DBS because the device is more expensive and the operating time is longer). Of the 70,000 people in Ontario with epilepsy, about 1,400 (300 children and 1,110 adults) may be candidates for VNS to reduce their seizures 13).

Complications and failure of the device can result from lead fracture, device malfunction, disconnection, or battery displacement and can result in a variety of symptoms.

D’Agostino et al., present an interesting case of stimulator malfunction with increased impedance change seen only with a change in head position.

The patient is a 25-year-old male with a vagal nerve stimulator (VNs) placed for medically refractory epilepsy who presented with neck pain and an electrical pulling sensation in his neck whenever he turned his head to the right. Initial interrogation of the VNs showed normal impedance. Subsequent interrogation with the patient’s head turned found increased impedance only when the head was turned to the right. The patient had successful removal and replacement of the device with resolution of his preoperative complaints. Partial lead fracture was seen at explant.

Vagus nerve stimulator malfunction can present in atypical ways. Positional maneuvers may help with its timely diagnosis 14).

It is still difficult to predict which patients will respond to VNS treatment and to what extent.

Liu et al., aimed to explore the relationship between preoperative heart rate variability (HRV) and VNS outcome. 50 healthy control subjects and 63 DRE patients who had received VNS implants and had at least one year of follow up were included. The preoperative HRV were analyzed by traditional linear methods and heart rhythm complexity analyses with multiscale entropy (MSE). DRE patients had significantly lower complexity indices (CI) as well as traditional linear HRV measurements than healthy controls. We also found that non-responders0 had significantly lower preoperative CI including Area 1-5, Area 6-15 and Area 6-20 than those in the responders0 while those of the non-responders50 had significantly lower RMSSD, pNN50, VLF, LF, HF, TP and LF/HF than the responders50. In receiver operating characteristic (ROC) curve analysis, Area 6-20 and RMSSD had the greatest discriminatory power for the responders0 and non-responders0, responders50 and non-responders50, respectively. Our results suggest that preoperative assessment of HRV by linear and MSE analysis can help in predicting VNS outcomes in patients with DRE 15).


Data suggest that sudden unexpected death in epilepsy patients (SUDEP) risk significantly decreases during long-term follow-up of patients with refractory epilepsy receiving VNS Therapy. This finding might reflect several factors, including the natural long-term dynamic of SUDEP rate, attrition, and the impact of VNS Therapy. The role of each of these factors cannot be confirmed due to the limitations of the study 16).

Boon et al., conducted a systematic review on the currently available neurostimulation modalities primarily with regard to effectiveness and safety.

For vagus nerve stimulation (VNS), there is moderate-quality evidence for its effectiveness in adults with drug-resistant partial epilepsies. Moderate-to-low-quality evidence supports the efficacy and safety of deep brain stimulation (DBS) and responsive neurostimulation (RNS) in patients with DRE. There is moderate-to-very low-quality evidence that transcranial direct current stimulation (tDCS) is effective or well tolerated. For transcutaneous vagus nerve stimulation (tVNS), transcranial magnetic stimulation (TMS) and trigeminal nerve stimulation (TNS), there are insufficient data to support the efficacy of any of these modalities for DRE. These treatment modalities, nevertheless, appear well tolerated, with no severe adverse events reported.

Head-to-head comparison of treatment modalities such as VNS, DBS and RNS across different epileptic syndromes are required to decide which treatment modality is the most effective for a given patient scenario. Such studies are challenging and it is unlikely that data will be available in the near future. Additional data collection on potentially promising noninvasive neurostimulation modalities like tVNS, TMS, TNS and tDCS is warranted to get a more precise estimate of their therapeutic benefit and long-term safety 17).

see Vagus nerve stimulation for drug resistant epilepsy case series.

Arhan et al., describe the first child with drug-resistant epilepsy in whom vagus nerve stimulation aggravated seizures and emerged status epilepticus after the increase in vagal nerve stimulation current output.

A 13-year-old girl presented with refractory secondary generalized focal epilepsy. Vagal nerve stimulator was implanted because of drug-resistant epilepsy. After the increase of vagal nerve stimulator current output to a relatively high level, the patient experienced seizure aggravation and status epilepticus.

They conclude that vagus nerve stimulation may induce paradoxical seizures and may lead to status epilepticus, similarly to some antiepileptic drugs 18).


1)

Toffa DH, Touma L, El Meskine T, Bouthillier A, Nguyen DK. Learnings from 30 years of reported efficacy and safety of vagus nerve stimulation (VNS) for epilepsy treatment: A critical review. Seizure. 2020 Oct 10;83:104-123. doi: 10.1016/j.seizure.2020.09.027. Epub ahead of print. PMID: 33120323.
2)

Yamamoto T. Vagus nerve stimulation therapy: indications, programing, and outcomes. Neurol Med Chir (Tokyo). 2015;55(5):407-15. doi: 10.2176/nmc.ra.2014-0405. Epub 2015 Apr 28. Review. PubMed PMID: 25925759; PubMed Central PMCID: PMC4628168.
3)

Alexopoulos AV, Kotagal P, Loddenkemper T, Hammel J, Bingaman WE (2006) Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy. Seizure 15: 491–503. pmid:16859931 doi: 10.1016/j.seizure.2006.06.002
4)

Chambers A, Bowen JM (2013) Electrical stimulation for drug-resistant epilepsy: an evidence-based analysis. Ont Health Technol Assess Ser 13: 1–37. pmid:24379898
5)

Coady MA, Adler F, Davila JJ, Gahtan V (2000) Nonrecurrent laryngeal nerve during carotid artery surgery: case report and literature review. J Vasc Surg 32: 192–196. pmid:10876223 doi: 10.1067/mva.2000.105680
6)

Elliott RE, Rodgers SD, Bassani L, Morsi A, Geller EB, et al. (2011) Vagus nerve stimulation for children with treatment-resistant epilepsy: a consecutive series of 141 cases. J Neurosurg Pediatr 7: 491–500. doi: 10.3171/2011.2.PEDS10505. pmid:21529189
7)

Englot DJ, Chang EF, Auguste KI (2011) Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. Journal of neurosurgery 115: 1248–1255. doi: 10.3171/2011.7.JNS11977. pmid:21838505
8)

Milby AH, Halpern CH, Baltuch GH (2009) Vagus nerve stimulation in the treatment of refractory epilepsy. Neurotherapeutics 6: 228–237. doi: 10.1016/j.nurt.2009.01.010. pmid:19332314
9)

Rutecki P (1990) Anatomical, physiological, and theoretical basis for the antiepileptic effect of vagus nerve stimulation. Epilepsia 31 Suppl 2: S1–6. pmid:2226361 doi: 10.1111/j.1528-1157.1990.tb05843.x
10)

Tanganelli P, Ferrero S, Colotto P, Regesta G (2002) Vagus nerve stimulation for treatment of medically intractable seizures. Evaluation of long-term outcome. Clin Neurol Neurosurg 105: 9–13. pmid:12445916 doi: 10.1016/s0303-8467(02)00018-5
11)

Bari AA, Pouratian N. Brain imaging correlates of peripheral nerve stimulation. Surg Neurol Int. 2012;3(Suppl 4):S260-8. doi: 10.4103/2152-7806.103016. Epub 2012 Oct 31. PubMed PMID: 23230531; PubMed Central PMCID: PMC3514912.
12)

Connor DE Jr, Nixon M, Nanda A, Guthikonda B. Vagal nerve stimulation for the treatment of medically refractory epilepsy: a review of the current literature. Neurosurg Focus. 2012 Mar;32(3):E12. doi: 10.3171/2011.12.FOCUS11328. Review. PubMed PMID: 22380853.
13)

Chambers A, Bowen JM. Electrical stimulation for drug-resistant epilepsy: an evidence-based analysis. Ont Health Technol Assess Ser. 2013 Oct 1;13(18):1-37. eCollection 2013. Review. PubMed PMID: 24228081; PubMed Central PMCID: PMC3817921.
14)

D’Agostino E, Makler V, Bauer DF. Vagal Nerve Stimulator Malfunction with Change in Neck Position: Case Report and Literature Review. World Neurosurg. 2018 Mar 16. pii: S1878-8750(18)30551-5. doi: 10.1016/j.wneu.2018.03.073. [Epub ahead of print] PubMed PMID: 29555606.
15)

Liu HY, Yang Z, Meng FG, Guan YG, Ma YS, Liang SL, Lin JL, Pan LS, Zhao MM, Qu W, Hao HW, Luan GM, Zhang JG, Li LM. Preoperative Heart Rate Variability as Predictors of Vagus Nerve Stimulation Outcome in Patients with Drug-resistant Epilepsy. Sci Rep. 2018 Mar 1;8(1):3856. doi: 10.1038/s41598-018-21669-3. PubMed PMID: 29497072; PubMed Central PMCID: PMC5832772.
16)

Ryvlin P, So EL, Gordon CM, Hesdorffer DC, Sperling MR, Devinsky O, Bunker MT, Olin B, Friedman D. Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with VNS therapy. Epilepsia. 2018 Mar;59(3):562-572. doi: 10.1111/epi.14002. Epub 2018 Jan 16. PubMed PMID: 29336017.
17)

Boon P, De Cock E, Mertens A, Trinka E. Neurostimulation for drug-resistant epilepsy: a systematic review of clinical evidence for efficacy, safety, contraindications and predictors for response. Curr Opin Neurol. 2018 Apr;31(2):198-210. doi: 10.1097/WCO.0000000000000534. PubMed PMID: 29493559.
18)

Arhan E, Serdaroğlu A, Hirfanoğlu T, Kurt G. Aggravation of seizures and status epilepticus after vagal nerve stimulation therapy: the first pediatric case and review of the literature. Childs Nerv Syst. 2018 Apr 22. doi: 10.1007/s00381-018-3806-x. [Epub ahead of print] PubMed PMID: 29680919.

Asleep subthalamic deep brain stimulation for Parkinson’s disease

Asleep subthalamic deep brain stimulation for Parkinson’s disease

Recent advances in methods used for deep brain stimulation (DBS) include subthalamic nucleus electrode implantation in the “asleep” patient without the traditional use of microelectrode recordings or intraoperative test stimulation.

Meta-Analysis

2019

Liu et al. systematically reviewed the literature to compare the efficacy and safety of awake and asleep deep brain stimulation surgery. They identified cohort studies from the Cochrane libraryMEDLINE, and EMBASE (January 1970 to August 2019) by using Review Manager 5.3 software to conduct a meta-analysis following the PRISMA guidelines. Fourteen cohort studies involving 1,523 patients were included. The meta-analysis results showed that there were no significant differences between the GA and LA groups in UPDRSIII score improvement (standard mean difference [SMD] 0.06; 95% CI -0.16 to 0.28; p = 0.60), postoperative LEDD requirement (SMD -0.17; 95% CI -0.44 to 0.12; p = 0.23), or operation time (SMD 0.18; 95% CI -0.31 to 0.67; p = 0.47). Additionally, there was no significant difference in the incidence of adverse events (OR 0.98; 95% CI 0.53-1.80; p = 0.94), including postoperative speech disturbance and intracranial hemorrhage. However, the volume of intracranial air was significantly lower in the GA group than that in the LA group. In a subgroup analysis, there was no significant difference in clinical efficacy between the microelectrode recording (MER) and non-MER groups. We demonstrated equivalent clinical outcomes of DBS surgery between GA and LA in terms of improvement of symptoms and the incidence of adverse events. Key Messages: MER might not be necessary for DBS implantation. For patients who cannot tolerate DBS surgery while being awake, GA should be an appropriate alternative 1).

Case series

A retrospective review of clinical outcomes of 152 consecutive patients. Their outcomes at 1 yr postimplantation are reported; these include Unified Parkinson’s Disease Rating Scale (UPDRS) assessment, Mobility Tinetti TestPDQ-39 quality of life assessment, Mattis Dementia Rating ScaleBeck Depression Inventory, and Beck Anxiety Inventory. They also report on a new parietal trajectory for electrode implantation.

UPDRS III improved from 39 to 20.5 (47%, P < .001). The total UPDRS score improved from 67.6 to 36.4 (46%, P < .001). UPDRS II scores improved from 18.9 to 10.5 (44%, P < .001) and UPDRS IV scores improved from 7.1 to 3.6 (49%, P < .001). There was a significant reduction in levodopa equivalent daily dose after surgery (mean: 35%, P < .001). PDQ-39 summary index improved by a mean of 7.1 points. There was no significant difference found in clinical outcomes between the frontal and parietal approaches.

“Asleep” robot-assisted DBS of the subthalamic nucleus demonstrates comparable outcomes with traditional techniques in the treatment of Parkinson’s disease. 2).


The objective of a study of Senemmar et al. was to investigate whether asleep deep brain stimulation surgery of the subthalamic nucleus (STN) improves therapeutic window (TW) for both directional (dDBS) and omnidirectional (oDBS) stimulation in a large single-center population.

A total of 104 consecutive patients with Parkinson’s disease (PD) undergoing STN-DBS surgery (80 asleep and 24 awake) were compared regarding TW, therapeutic thresholdside effect threshold, improvement of Unified PD Rating Scale motor score (UPDRS-III) and degree of levodopa equivalent daily dose (LEDD) reduction.

Asleep DBS surgery led to significantly wider TW compared to awake surgery for both dDBS and oDBS. However, dDBS further increased TW compared to oDBS in the asleep group only and not in the awake group. Clinical efficacy in terms of UPDRS-III improvement and LEDD reduction did not differ between groups.

The study provides first evidence for improvement of therapeutic window by asleep surgery compared to awake surgery, which can be strengthened further by dDBS. These results support the notion of preferring asleep over awake surgery but needs to be confirmed by prospective trial3).


Clinical outcome studies have shown that “asleep” DBS lead placement, performed using intraoperative imaging with stereotactic accuracy as the surgical endpoint, has motor outcomes comparable to traditional “awake” DBS using microelectrode recording (MER), but with shorter case times and improved speech fluency 4).


Ninety-six patients were retrospectively matched pairwise (48 asleep and 48 awake) and compared regarding improvement of Unified PD Rating Scale Motor Score (UPDRS-III), cognitive function, Levodopa-equivalent-daily-dose (LEDD), stimulation amplitudes, side effects, surgery duration, and complication rates. Routine testing took place at three months and one year postoperatively.

Results: Chronic DBS effects (UPDRS-III without medication and with stimulation on [OFF/ON]) significantly improved UPDRS-III only after awake surgery at three months and in both groups one year postoperatively. Acute effects (percentage UPDRS-III reduction after activation of stimulation) were also significantly better after awake surgery at three months but not at one year compared to asleep surgery. UPDRS-III subitems “freezing” and “speech” were significantly worse after asleep surgery at three months and one year, respectively. LEDD was significantly lower after awake surgery only one week postoperatively. The other measures did not differ between groups.

Overall motor function improved faster in the awake surgery group, but the difference ceased after one year. However, axial subitems were worse in the asleep surgery group suggesting that worsening of axial symptoms was risked improving overall motor function. Awake surgery still seems advantageous for STN-DBS in PD, although asleep surgery may be considered with lower threshold in patients not suitable for awake surgery 5).

References

1)

Liu Z, He S, Li L. General Anesthesia versus Local Anesthesia for Deep Brain Stimulation in Parkinson’s Disease: A Meta-Analysis. Stereotact Funct Neurosurg. 2019;97(5-6):381-390. doi:10.1159/000505079
2)

Moran CH, Pietrzyk M, Sarangmat N, Gerard CS, Barua N, Ashida R, Whone A, Szewczyk-Krolikowski K, Mooney L, Gill SS. Clinical Outcome of “Asleep” Deep Brain Stimulation for Parkinson Disease Using Robot-Assisted Delivery and Anatomic Targeting of the Subthalamic Nucleus: A Series of 152 Patients. Neurosurgery. 2020 Sep 28:nyaa367. doi: 10.1093/neuros/nyaa367. Epub ahead of print. PMID: 32985669.
3)

Senemmar F, Hartmann CJ, Slotty PJ, Vesper J, Schnitzler A, Groiss SJ. Asleep Surgery May Improve the Therapeutic Window for Deep Brain Stimulation of the Subthalamic Nucleus [published online ahead of print, 2020 Jul 13]. Neuromodulation. 2020;10.1111/ner.13237. doi:10.1111/ner.13237
4)

Mirzadeh Z, Chen T, Chapple KM, Lambert M, Karis JP, Dhall R, Ponce FA. Procedural Variables Influencing Stereotactic Accuracy and Efficiency in Deep Brain Stimulation Surgery. Oper Neurosurg (Hagerstown). 2018 Oct 18. doi: 10.1093/ons/opy291. [Epub ahead of print] PubMed PMID: 30339204.
5)

Blasberg F, Wojtecki L, Elben S, Slotty PJ, Vesper J, Schnitzler A, Groiss SJ. Comparison of Awake vs. Asleep Surgery for Subthalamic Deep Brain Stimulation in Parkinson’s Disease. Neuromodulation. 2018 Aug;21(6):541-547. doi: 10.1111/ner.12766. Epub 2018 Mar 13. PubMed PMID: 29532

Occipital nerve stimulation for cluster headache

Occipital nerve stimulation for cluster headache

Occipital nerve stimulation (ONS) has been proposed chronic cluster headache treatment (rCCH) but its efficacy has only been showed in small short-term series.

Leplus et al. evaluated 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption.

At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%).

The results showed that longterm efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients 1).


33 patients, of whom 16 had chronic migraine (CM), nine had chronic cluster headache (CCH), and six had secondary headache disorders. PENS was given using Algotec® disposable 21 gauge PENS therapy probes (8 cm) to the occipital nerve ipsilateral to the pain (or bilaterally in cases of bilateral pain). Stimulation was delivered at 2 Hz/100 Hz, at 3 cycles/s, between 1.2 and 2.5 V depending on patient tolerability, for 25-28 min.

Six of nine patients with CCH improved significantly after the first session. In all patients with CCH, PENS therapy was well tolerated, with no significant adverse events reported. One patient with CCH reverted to an episodic cluster. Only four patients with CM experienced any benefit.

PENS therapy shows potential as a relatively non-invasive, low-risk, and inexpensive component of the treatment options for refractory primary headache disorders, particularly CCH 2).


Seventeen patients (12 CM and 5 CCH) were treated with bilateral burst pattern ONS, including 4 who had previously had tonic ONS. Results were assessed in terms of the frequency of headaches (number of headache days per month for CM, and number of attacks per day for CCH) and their intensity on the numeric pain rating scale.

Burst ONS produced a statistically significant mean reduction of 10.2 headache days per month in CM. In CCH, there were significant mean reductions in headache frequency (92%) and intensity (42%).

Paraesthesia is not necessary for good quality analgesia in ONS. Larger studies will be required to determine whether the efficacies of the two stimulation modes differ. Burst ONS is imperceptible and therefore potentially amenable to robustly blinded clinical trials 3).


Eight patients with medically intractable chronic cluster headache were implanted in the suboccipital region with electrodes for occipital nerve stimulation. Other than the first patient, who was initially stimulated unilaterally before being stimulated bilaterally, all patients were stimulated bilaterally during treatment.

At a median follow-up of 20 months (range 6-27 months for bilateral stimulation), six of eight patients reported responses that were sufficiently meaningful for them to recommend the treatment to similarly affected patients with chronic cluster headache. Two patients noticed a substantial improvement (90% and 95%) in their attacks; three patients noticed a moderate improvement (40%, 60%, and 20-80%) and one reported mild improvement (25%). Improvements occurred in both frequency and severity of attacks. These changes took place over weeks or months, although attacks returned in days when the device malfunctioned (eg, with battery depletion). Adverse events of concern were lead migrations in one patient and battery depletion requiring replacement in four.

Occipital nerve stimulation in cluster headache seems to offer a safe, effective treatment option that could begin a new era of neurostimulation therapy for primary headache syndromes 4).

References

1)

Leplus A, Fontaine D, Donnet A, Regis J, Lucas C, Buisset N, Blond S, Raoul S, Guegan-Massardier E, Derrey S, Jarraya B, Dang-Vu B, Bourdain F, Valade D, Roos C, Creach C, Chabardes S, Giraud P, Voirin J, Bloch J, Colnat-Coulbois S, Caire F, Rigoard P, Tran L, Cruzel C, Lantéri-Minet M; French ONS registry group. LongTerm Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache. Neurosurgery. 2020 Sep 28:nyaa373. doi: 10.1093/neuros/nyaa373. Epub ahead of print. PMID: 32985662.
2)

Weatherall MW, Nandi D. Percutaneous electrical nerve stimulation (PENS) therapy for refractory primary headache disorders: a pilot study. Br J Neurosurg. 2019 Oct 3:1-5. doi: 10.1080/02688697.2019.1671951. [Epub ahead of print] PubMed PMID: 31578882.
3)

Garcia-Ortega R, Edwards T, Moir L, Aziz TZ, Green AL, FitzGerald JJ. Burst Occipital Nerve Stimulation for Chronic Migraine and Chronic Cluster Headache. Neuromodulation. 2019 Jul;22(5):638-644. doi: 10.1111/ner.12977. Epub 2019 Jun 14. PubMed PMID: 31199547.
4)

Burns B, Watkins L, Goadsby PJ. Treatment of medically intractable cluster headache by occipital nerve stimulationlongterm follow-up of 8 patients. Lancet. 2007; 369:1099–1106
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