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  • 1
    In: Cephalalgia, SAGE Publications, Vol. 33, No. 10 ( 2013-07), p. 816-830
    Abstract: The pain and autonomic symptoms of cluster headache (CH) result from activation of the trigeminal parasympathetic reflex, mediated through the sphenopalatine ganglion (SPG). We investigated the safety and efficacy of on-demand SPG stimulation for chronic CH (CCH). Methods A multicenter, multiple CH attack study of an implantable on-demand SPG neurostimulator was conducted in patients suffering from refractory CCH. Each CH attack was randomly treated with full, sub-perception, or sham stimulation. Pain relief at 15 minutes following SPG stimulation and device- or procedure-related serious adverse events (SAEs) were evaluated. Findings Thirty-two patients were enrolled and 28 completed the randomized experimental period. Pain relief was achieved in 67.1% of full stimulation-treated attacks compared to 7.4% of sham-treated and 7.3% of sub-perception-treated attacks ( p  〈  0.0001). Nineteen of 28 (68%) patients experienced a clinically significant improvement: seven (25%) achieved pain relief in ≥50% of treated attacks, 10 (36%), a ≥50% reduction in attack frequency, and two (7%), both. Five SAEs occurred and most patients (81%) experienced transient, mild/moderate loss of sensation within distinct maxillary nerve regions; 65% of events resolved within three months. Interpretation On-demand SPG stimulation using the ATI Neurostimulation System is an effective novel therapy for CCH sufferers, with dual beneficial effects, acute pain relief and observed attack prevention, and has an acceptable safety profile compared to similar surgical procedures.
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
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  • 2
    In: Cephalalgia, SAGE Publications, Vol. 40, No. 9 ( 2020-08), p. 966-977
    Abstract: Cephalic autonomic symptoms occur in 27‒73% of migraine patients during attacks. The role of parasympathetic activation in migraine attack initiation remains elusive. Low frequency stimulation of the sphenopalatine ganglion increases parasympathetic outflow. In this study, we hypothesized that low frequency stimulation of the sphenopalatine ganglion would provoke migraine-like attacks in migraine patients. Methods In a double-blind randomized sham-controlled crossover study, 12 migraine patients with a sphenopalatine ganglion neurostimulator received low frequency or sham stimulation for 30 min on two separate days. We recorded headache characteristics, cephalic autonomic symptoms, ipsilateral mechanical perception and pain thresholds, mean blood flow velocity in the middle cerebral artery (V MCA ) and diameter of the superficial temporal artery during and after stimulation. Results Five patients (42%) reported a migraine-like attack after low frequency stimulation compared to six patients (50%) after sham ( p = 1.000). We found a significant increase in mechanical detection thresholds during low frequency stimulation compared to baseline ( p = 0.007). Occurrence of cephalic autonomic symptoms and changes in mechanical perception thresholds, V MCA and diameter of the superficial temporal artery showed no difference between low frequency stimulation compared to sham ( p = 0.533). Conclusion Low frequency stimulation of the sphenopalatine ganglion did not induce migraine-like attacks or autonomic symptoms in migraine patients. These data suggest that increased parasympathetic outflow by the sphenopalatine ganglion neurostimulator does not initiate migraine-like attacks. Study protocol: ClinicalTrials.gov registration number NCT02510742
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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  • 3
    In: Cephalalgia, SAGE Publications, Vol. 37, No. 5 ( 2017-04), p. 423-434
    Abstract: The sphenopalatine ganglion (SPG) plays a pivotal role in cluster headache (CH) pathophysiology as the major efferent parasympathetic relay. We evaluated the long-term effectiveness of SPG stimulation in medically refractory, chronic CH patients. Methods Thirty-three patients were enrolled in an open-label follow-up study of the original Pathway CH-1 study, and participated through 24 months post-insertion of a microstimulator. Response to therapy was defined as acute effectiveness in ≥ 50% of attacks or a ≥ 50% reduction in attack frequency versus baseline. Results In total, 5956 attacks (180.5 ± 344.8, range 2–1581 per patient) were evaluated. At 24 months, 45% ( n = 15) of patients were acute responders. Among acute responders, a total of 4340 attacks had been treated, and in 78% of these, effective therapy was achieved using only SPG stimulation (relief from moderate or greater pain or freedom from mild pain or greater). A frequency response was observed in 33% ( n = 11) of patients with a mean reduction of attack frequency of 83% versus baseline. In total, 61% (20/33) of all patients were either acute or frequency responders or both. The majority maintained their therapeutic response through the 24-month evaluation. Conclusions In the population of disabled, medically refractory chronic CH patients treated in this study, SPG stimulation is an effective acute therapy in 45% of patients, offering sustained effectiveness over 24 months of observation. In addition, a maintained, clinically relevant reduction of attack frequency was observed in a third of patients. These long-term data provide support for the use of SPG stimulation for disabled patients and should be considered after medical treatments fail, are not tolerated or are inconvenient for the patients.
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2019999-5
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  • 4
    In: Cephalalgia, SAGE Publications, Vol. 38, No. 8 ( 2018-07), p. 1418-1428
    Abstract: Low frequency (LF) stimulation of the sphenopalatine ganglion (SPG) may increase parasympathetic outflow and provoke cluster headache (CH) attacks in CH patients implanted with an SPG neurostimulator. Methods In a double-blind randomized sham-controlled crossover study, 20 CH patients received LF or sham stimulation for 30 min on two separate days. We recorded headache characteristics, cephalic autonomic symptoms (CAS), plasma levels of parasympathetic markers such as pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal peptide (VIP), and mechanical detection and pain thresholds as a marker of sensory modulation. Results In the immediate phase (0–60 min), 16 (80%) patients experienced CAS after LF stimulation, while nine patients (45%) reported CAS after sham ( p = 0.046). We found no difference in induction of cluster-like attacks between LF stimulation (n = 7) and sham stimulation (n = 5) ( p = 0.724). There was no difference in mechanical detection and pain thresholds, and in PACAP and VIP plasma concentrations between LF and sham stimulation ( p ≥ 0.162). Conclusion LF stimulation of the SPG induced autonomic symptoms, but no CH attacks. These data suggest that increased parasympathetic outflow is not sufficient to induce CH attacks in patients. Study protocol ClinicalTrials.gov registration number NCT02510729
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
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  • 5
    In: The Journal of Headache and Pain, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2016-12)
    Type of Medium: Online Resource
    ISSN: 1129-2369 , 1129-2377
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2020168-0
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