Headache: Using Neuromodulation as Therapy

Transcription

1 Headache: Using Neuromodulation as Therapy Rashmi Halker, MD, FAHS Assistant Professor of Neurology Department of Neurology Mayo Clinic Phoenix Arizona

2 Disclosures Nothing to disclose 2013 MFMER slide-2

3 Objectives Discuss invasive neuromodulation options for headache Deep brain stimulation Occipital nerve stimulation Sphenopalataine ganglion stimulation Discuss noninvasive neuromodulation options for headache Vagal nerve stimulation Supraorbital nerve stimulation Single-pulse transcranial magnetic stimulation 2013 MFMER slide-3

4 Migraine is the 3 rd most prevalent medical disorder on the planet Migraine accounts for > 50% of the disability burden attributable to all neurological disease worldwide. Overall, it is the 4 th ranking cause among women and the 6 th ranking cause of all disease-associated disability worldwide. Lancet 2012; 380:

5 Neuromodulation: The Early Days 43 AD Scribonius Largus, Court Physician of Emperor Claudius: To immediately remove and permanently cure a headache,. a live black torpedo is put on the place which is in pain, until the pain ceases and the part grows numb.

6 Neuromodulation Methods For Headache Refractory headaches Deep brain stimulation [Hypothalamic] Occipital nerve stimulation [ONS] Sphenopalatine ganglion stimulation [SPGS] Vagal nerve stimulation [VNS] Supraorbital nerve stimulation [Cefaly] Single pulse transcranial magnetic stimulation [stms] Vestibular neuromodulation Invasive Non-Invasive Any headache

7 Hypothalamic Deep Brain Stimulation for Drug- Resistant Chronic Cluster Headache Outcome Number % Pain Free Response (>50%) Total 41/64 64% Leone et al Cephalalgia 2015 Lyons M, et al. J Neurosurg 2009; Leone M, et al. Ann Neurol;2005: Leone M, et al. Cephalalgia 2008;28:

8 Hypothalamic Deep Brain Stimulation for Drug- Resistant Chronic Cluster Headache Efficacy (median 8.7 year follow up in 17 patients) 6 are almost pain-free; Stimulators off for a median of 3 years 6 no longer experience daily attacks (ECH with long-lasting remissions) 5 did not improve Adverse Events Electrode displacement (n=2) Infection (electrode n=3; generator n=1) Electrode malpositioning (n=1) Transient nonsymptomatic third ventricle hemorrhage (n=1) Persistent slight muscle weakness on one side (n=1) Seizure (n=1) Leone M et al. Pain. 2013;154:89 94.

9 Occipital Nerve Stimulation

10 Bilateral Extracranial Stimulation of the Greater Occipital Nerve for Chronic Migraine Three failed RCTs Patients reported in literature >500

11 ONS for Chronic Migraine Migraine Headache Days Visit Control Group (n=52) Active Group (n=105) P-Value Baseline Mean (± std) 20,1 (± 7,2) 22,4 (± 6,9) 0,049 Week 12 Mean Change 1-3,0 (14,9%) -6,1 (27,2%) 0,008 Difference (95% CI) -3,1 (-5,4, -0,8) Silberstein SD, et al. Cephalalgia 2012;32(16) :

12 Occipital Nerve Stimulation for CM: Long-term Data Adults with chronic migraine (N=157); 12 weeks randomized, 40 weeks open label follow-up Efficacy Significant reduction in headache days (P<0.001) and disability (p<0.001) 50% reduction in headache days and/or pain intensity: 47.8% 2/3 of patients satisfied Adverse effects: 70% 8.6% required hospitalization 40.7% required surgical intervention Dodick DW et al. Cephalalgia. 2015;35:

13 Occipital Nerve Stimulation for Trigeminal Autonomic Cephalalgias Headache Treated Outcomes Hemicrania continua 1,2 >80% response (n=6/8) Chronic cluster % responder rate (n=39/53 >50% improvement) SUNCT (n=5) and SUNA (n=1) 9 >50% benefit (n=4 patients nearly pain-free) 1. Burns B et al. Lancet Neurol. 2008; 2. Dodick D et al. Headache. 2007; 3.Strand NH et al. Pain Physician. 2011;14: ; 4. de Quintana-Schmidt C et al. Rev Neurol 2010;51:19 26.; 5. Burns et al. Neurology. 2009;72: ; 6. Magis D et al. Lancet Neurology. 2007;6: ; 7. Fontaine D et al. Cephalalgia. 2011;31: ; 8. Mueller OM et al. Cen Eur Neurosurg. 2011;72: ; 9. Shanahan et al. Cephalalgia. 2009;29(suppl 1):150.

14 Long-term Outcome in Drug-resistant Chronic Cluster Headache (ONS) 35 patients with mean 6.7 years DR-CCH followed for 6.1 years ( years) 20/35 (68%) > 50% reduction in headaches per day. 10 non-responders; 5 initial responders efficacy waned. Adverse events: battery change (21); lead migration, malfunction, tip erosion (10). Leone M, et al. Cephalalgia 2016

15 Literature-Based Adverse Event Rate

16 Deactivation of Migraine/Cluster Generator? Activation of Descending Opioid System in Responders Magis et al. BMC Neurology. 2011;11:25; Matharu et al. Brain. 2003;127:

17 Sphenopalatine Ganglion Stimulation Microstimulator System Microstimulator requires no batteries Insertion via trans-oral procedure Activated by external hand-held wireless remote controller Patient controlled, on-demand therapy

18 SPG Stimulation for Cluster Headache: A randomized, Sham-Controlled Study Responders 67.1% (FS) vs 7.4% (sham) vs 7.3% (SP) 43% had >50% reduction in CH attacks p< Schoenen J, et al. Cephalalgia 2013;;33,: :

19 SPG stimulation acute and frequency responses through 2 years post-implant 78% effective therapy in ~4000 attacks treated in responders 83% reduction in attack frequency in 33% of patients Schoenen J, et al. Cephalalgia 2013;;33,: :

20 SPG for the Treatment of Chronic Cluster Headache Primary Efficacy: Proportion of cluster attacks relieved at 15 minutes (7mo). Primary Safety: All SAEs through the completion of the Open Label Period. N=120 July 2014-January 2017 NCT

21 Neuromodulation Methods For Headache Refractory headaches Deep brain stimulation [Hypothalamic] Occipital nerve stimulation [ONS] Sphenopalatine ganglion stimulation [SPGS] Vagal nerve stimulation [VNS] Supraorbital nerve stimulation [Cefaly] Single pulse transcranial magnetic stimulation [stms] Vestibular neuromodulation Invasive Non-Invasive Any headache

22 Supraorbital Transcutaneous Stimulation

23 Supraorbital Transcutaneous Stimulation Double-blind, sham-controlled trial, n=67 Stimulation 250 µs, 60 Hz, 16 ma, 20 min / day 3 months Active Sham P-value Decrease in mean migraine days % responder rate 38.1% 12.1% 0.023* Schoenen J et al, Neurology 2013

24 Compliments Tony Barker Prescription controlled by SIM card

25 Lipton et al., Lancet Neurol 2010;9:373-80

26 ESPOUSE: Mean Reduction in Headache Days Performance Goal = Presented EHMTIC 2016; Glasgow

27 Non-Invasive Vagus Nerve Stimulator (nvns) Selectively stimulates lowthreshold myelinated afferent A fibers, not high-threshold C-fibers Delivers 90-second stimulations that can be used repeatedly Maximum 24V and 60mA output

28 VNS: Mean Change in CH attacks per week

29 Summary Deep-brain (hypothalamic), SPG, and vagus nerve stimulation emerging as effective for treatment of cluster headache Non-invasive technologies preferred Occipital nerve stimulation may be effective for wide range of primary headache disorders stms, supraorbital nerve stimulation, and vestibular neuromodulation

30 Summary *** ** * MIGRAINE CLUSTER * *** * Phase III ** FDA Submission *** FDA approved