Pilot study of sphenopalatine injection of onabotulinumtoxinA for the treatment of intractable chronic cluster headache

Objective The main object of this pilot study was to investigate the safety of administering onabotulinumtoxinA (BTA) towards the sphenopalatine ganglion (SPG) in intractable chronic cluster headache. Efficacy data were also collected to provide indication on whether future placebo-controlled studies should be performed. Method In a prospective, open-label, uncontrolled study, we performed a single injection of 25 IU ( n = 5) or 50 IU BTA ( n = 5) towards the SPG in 10 patients with intractable chronic cluster headache with a follow-up of 24 weeks. The primary outcome was adverse events (AEs) and the main efficacy outcome was attack frequency in weeks 3 and 4 post-treatment. Results A total of 11 AEs were registered. There was one severe adverse event (SAE): posterior epistaxis. The number of cluster headache attacks (main efficacy outcome) was statistically significantly reduced in the intention-to-treat analysis from 18 ± 12 per week in baseline to 11 ± 14 ( p = 0.038) in weeks 3 and 4, and five out of 10 patients had at least 50% reduction of attack frequency compared to baseline. The cluster attack frequency was significantly reduced for five out of six months post-treatment. Conclusion Randomised, placebo-controlled studies are warranted to establish the potential of this possible novel treatment of cluster headache.

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Pilot study of sphenopalatine injection of onabotulinumtoxinA for the treatment of intractable chronic migraine

Cephalalgia ◽

10.1177/0333102416648328 ◽

2016 ◽

Vol 37 (4) ◽

pp. 356-364 ◽

Cited By ~ 17

Author(s):

Daniel Fossum Bratbak ◽

Ståle Nordgård ◽

Lars Jacob Stovner ◽

Mattias Linde ◽

David W Dodick ◽

...

Keyword(s):

Pilot Study ◽

Adverse Events ◽

Chronic Migraine ◽

Severe Headache ◽

Sphenopalatine Ganglion ◽

Open Label ◽

Intention To Treat ◽

Efficacy Outcome ◽

The Face

Objective The main objective of this pilot study was to investigate the safety of administering onabotulinumtoxinA towards the sphenopalatine ganglion in 10 patients with intractable chronic migraine with an open, uncontrolled design. We also collected efficacy data to provide an indication as to whether future placebo-controlled studies should be performed. Method In a prospective, open-label, uncontrolled study after one-month baseline, we performed bilateral injections of 25 IU onabotulinumtoxinA (total dose 50 IU) toward the sphenopalatine ganglion in a single outpatient session in 10 patients with intractable migraine with a follow-up of 12 weeks. The primary outcome was adverse events and the main efficacy outcome was frequency of moderate and severe headache days in month 2 post-treatment compared to baseline. Results All 10 patients experienced a total of 25 adverse events. The majority of these were different types of local discomfort in the face and jaw, and none were classified as serious. In an intention-to-treat analysis of the main efficacy outcome, a statistically significant reduction of moderate and severe headache days in baseline versus month 2 was observed (16.3 ± 6.2 days baseline versus 7.6 ± 7.6 days month 2, p = 0.009). Eight out of 10 patients experienced an at least 50% reduction of moderate and severe headache days compared to baseline. Conclusion The result warrants randomised, placebo-controlled studies to establish both safety and efficacy of this potential novel treatment of chronic migraine.

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The effect of oral miltefosine in treatment of antimoniate resistant anthroponotic cutaneous leishmaniasis: An uncontrolled clinical trial

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009241 ◽

2021 ◽

Vol 15 (3) ◽

pp. e0009241

Author(s):

Masoumeh Tayyebi ◽

Emadodin Darchini-Maragheh ◽

Pouran Layegh ◽

Bita Kiafar ◽

Vahid Mashayekhi Goyonlo

Keyword(s):

Cutaneous Leishmaniasis ◽

Laboratory Data ◽

Post Treatment ◽

P Value ◽

Base Line ◽

Cure Rate ◽

Intention To Treat ◽

Days Of Therapy ◽

Treat Analysis

Background Recent circumstantial evidence suggests increasing number of Iranian patients with cutaneous leishmaniasis (CL) who are unresponsive to meglumine antimoniate (MA), the first line of treatment in Iran. Oral meltifosine was previously reported to be effective in visceral leishmaniasis as well CL. The current study is designed to determine efficacy and safety of oral miltefosine for the treatment of anthroponotic cutaneous leishmaniasis (ACL) cases who were refractory to MA in Iran. Methodology/Principal findings Miltefosine was orally administered for 27 patients with MA resistant ACL with approved L.tropica infection, at a dosage of ∼2.5 mg/kg daily for 28 days. Patients were evaluated on day 14 and 28, as well as 3, 6 and 12 month post treatment follow up sessions. Laboratory data were performed and repeated at each visit. Data were analyzed using SPSS version 17. Twenty-seven patients including 16 men (59.25%) and 11 women (40.74%) with mean age of 28.56 ± 4.8 (range 3–54 years old) were enrolled. Total number of lesions were 42 (1–4 in each patient). Most of lesions were on face (76.19%). Mean lesions’ induration size was 2.38 ± 0.73 cm at the base-line which significantly decreased to1.31 ± 0.58 cm and 0.61 ±0.49 cm after 14 and 28 days of therapy, respectively (p value <0.05). At 12-months follow-up post treatment, 22 patients had definite/partial cure (81.48%) including 17 definitely cured patients, corresponding to a cure rate of 68% on per protocol analysis, and 62.96% according to intention to treat analysis. Recurrence of lesion was only occurred in one patient (3.70%). Nausea was the most subjective complication during the therapy (33.33%). Conclusion Oral miltefosine could be an effective alternative for the treatment of MA-resistant ACL.

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WP1-1 Sphenopalatine ganglion stimulation for chronic cluster headache

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-abn.6 ◽

2019 ◽

Vol 90 (3) ◽

pp. e2.3-e2

Author(s):

S Miller ◽

S Lagrata ◽

M Matharu ◽

L Zrinzo

Keyword(s):

Cluster Headache ◽

Acute Effect ◽

Chronic Cluster Headache ◽

Headache Frequency ◽

Sphenopalatine Ganglion ◽

Open Label ◽

Vidian Canal ◽

The Uk ◽

Fluoroscopy Guidance

ObjectivesTo assess outcome of sphenopalatine ganglion stimulation (SPGS) in chronic cluster headache (CCH) in a UK centre.DesignUncontrolled open-label single centre prospective study.SubjectsNine patients with medically refractory CCH.MethodsParticipants underwent sphenopalatine ganglion stimulator implantation, ipsilateral to CCH symptoms via a gingival incision, with fluoroscopy guidance and dyna-CT confirmation of contact location adjacent to the Vidian canal in the pterygopalatine fossa. One month after surgery, the device was programmed. Patients were instructed to provide stimulation as early as possible after attack onset and at least twice daily. The primary outcome was change in headache frequency as well as adverse events.ResultsMean follow up was 14 months (SD 11.1, range: 3–31) with median reduction in headache frequency at last follow up of 73% (IQR: 67%–88%). At 3 months post op, 4/9 (45%) had at least 50% reduction in frequency of attacks; this increased to 8/9 patients (89%) at last follow up. Two patients became pain free (after 3 and 9 months). Preventative effects were seen in 7/9 and an acute effect in 2/9. One patient suffered numbness over the V2 distribution and did not respond to SPGS. The stimulator was removed 1 year later at the patient’s request. One wound infection settled with oral antibiotics.ConclusionsInitial data from the UK confirms the results from previous studies and compares well with the results of occipital nerve stimulation for CCH.

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Long-term effectiveness of sphenopalatine ganglion stimulation for cluster headache

Cephalalgia ◽

10.1177/0333102416649092 ◽

2016 ◽

Vol 37 (5) ◽

pp. 423-434 ◽

Cited By ~ 66

Author(s):

Tim P Jürgens ◽

Mads Barloese ◽

Arne May ◽

Jose Miguel Láinez ◽

Jean Schoenen ◽

...

Keyword(s):

Cluster Headache ◽

Response To Therapy ◽

Sphenopalatine Ganglion ◽

Attack Frequency ◽

Open Label ◽

Acute Therapy ◽

Medical Treatments ◽

Term Data

Objectives 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.

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EVALUATION OF A DIET AND ANTIBIOTICS TARGETING THE MICROBIOTA FOR TREATMENT OF MILD TO MODETARE ACTIVE PEDIARTIC ULCERATIVE COLITIS: AN OPEN LABEL PILOT STUDY

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.094 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S38-S38

Author(s):

Chen Sarbagili-Shabat ◽

Lindsey Albenberg ◽

Johan Van Limbergen ◽

Dror Weiner ◽

Michal Yaakov ◽

...

Keyword(s):

Ulcerative Colitis ◽

Pilot Study ◽

Dietary Intervention ◽

Activity Index ◽

Fecal Calprotectin ◽

Dietary Therapy ◽

The Novel ◽

Open Label ◽

Intention To Treat ◽

Stable Maintenance

Abstract Background Newer strategies that target the microbiome may offer an alternative therapeutic approach for Ulcerative Colitis (UC). We developed a novel diet that targets changes in the microbiome and barrier function that have been reported in UC. The goal of the current study was to evaluate the efficacy of two sequential induction of remission strategies that target the microbiota: the novel diet termed the ulcerative colitis diet (UCD) and an antibiotics cocktail combination in dietary non responders. Methods This was a prospective, single arm, open label, pilot study in patients aged 8–19, with a pediatric UC activity index (PUCAI) scores >10 and ≤45 on stable maintenance therapy (5ASA or thiopurines). PUCAI score was assessed at week 3 and 6. Patients failing to enter remission or intolerant to dietary therapy could receive an open label 14-day course of Amoxycillin, Metronidazole and Doxycycline (AMD), and had PUCAI scored at day 21. Response was defined a decline in PUCAI ≥ 10 points, remission as PUCAI< 10. The primary endpoint was intention to treat (ITT) remission at week 6 with diet as the sole intervention. Results Twenty-three children mean age of 15.1±2.9 years were enrolled. Two patients (1 responder, 1 remission) withdrew by 3 weeks, four required additional therapy by week 3, all were considered failures by ITT. Mean PUCAI decreased at week 3 and 6 from 34.5±9.8 to 21.7±14.9 and 17.6±17.2 respectively (P=0.005, P=0.001) at ITT analysis including all patients. Sixteen out of twenty-three patients (69.6%) responded by week 6. Ten of twenty-three (43.5%) achieved remission by week 6, and nine (39.1%) had clinical remission at week 6. The median fecal calprotectin (FC) level decreased in patients (n=5) who achieved remission from 630 (IQR, 332–1586) μg/g at week 0 to 230 (75–1298) μg/g at week 6. Eight patients received treatment with antibiotics after failing diet, 4/8 (50.0%) subsequently entered remission. Conclusion A dietary intervention called the UC Diet appears to be effective for induction of remission in children with mild to moderate UC. Sequential use of diet, followed by antibiotic therapy in dietary non responders, needs further evaluation as a microbiome directed steroid sparing therapy in patient’s refractory to 5ASA and thiopurines.

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Vidian Neurectomy for Management of Chronic Cluster Headache

Neurosurgery ◽

10.1093/neuros/nyy136 ◽

2018 ◽

Vol 84 (5) ◽

pp. 1059-1064 ◽

Cited By ~ 1

Author(s):

Shao-Cheng Liu ◽

Ming-Chang Kao ◽

Yun-Chen Huang ◽

Wan-Fu Su

Keyword(s):

Cluster Headache ◽

Chronic Cluster Headache ◽

Preliminary Evaluation ◽

Sphenopalatine Ganglion ◽

Attack Frequency ◽

Pain Disability Index ◽

Pain Disability ◽

Vidian Neurectomy ◽

Headache Onset ◽

Attack Intensity

Abstract BACKGROUND Management of chronic cluster headache (CCH) remains a challenging endeavor, and the optimal surgical approach for medically refractory CCH remains controversial. OBJECTIVE To conduct a preliminary evaluation of the efficacy and safety of vidian neurectomy (VN) in patients with medically refractory CCH. METHODS Between March 2013 and December 2015, 9 CCH patients, all of whom had failed to respond to conservative therapy, underwent VN with a precise nerve cut and maximal preservation of the sphenopalatine ganglion. Data included demographic variables, cluster headache onset and duration, mean attack frequency, mean attack intensity, and pain disability index measures pre- and through 12-mo postsurgery. RESULTS Seven of the 9 cases (77.8%) showed immediate improvement. Improvement was delayed by 1 mo in 1 patient, after which the surgical effects of pain relief were maintained throughout the follow-up period. One patient (11.1%) did not improve after surgery. One year after VN, patients’ mean attack frequency, mean attack intensity, and pain disability index decreased by 54.5%, 52.9%, and 56.4%, respectively. No patient experienced treatment-related side effects or complications. CONCLUSION VN is an effective treatment method for CCH patients. Precise Vidian nerve identification and maximal preservation of the sphenopalatine ganglion may achieve good surgical outcomes and dramatically improve quality of life among patients, without significant adverse events.

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A Randomized Trial Comparing Seven-Day Ranitidine Bismuth Citrate and Clarithromycin Dual Therapy to Seven-Day Omeprazole, Clarithromycin and Amoxicillin Triple Therapy for the Eradication ofHelicobacter pylori

Canadian Journal of Gastroenterology ◽

10.1155/2003/425293 ◽

2003 ◽

Vol 17 (9) ◽

pp. 533-538 ◽

Cited By ~ 3

Author(s):

Sander Veldhuyzen van Zanten ◽

Naoki Chiba ◽

Alan Barkun ◽

Carlo Fallone ◽

Alain Farley ◽

...

Keyword(s):

Dual Therapy ◽

Success Rates ◽

Open Label ◽

Treatment Allocation ◽

Ulcer Disease ◽

Intention To Treat ◽

Bismuth Citrate ◽

The Difference ◽

H Pylori

OBJECTIVE: To assessHelicobacter pylorieradication after one week dual ranitidine bismuth citrate-clarithromycin (RBC-C) or triple omeprazole, clarithromycin and amoxicillin (OCA) therapy.METHODS: In this multicentre Canadian trial,H pylori-positive patients with functional dyspepsia or inactive peptic ulcer disease were randomized to open-label treatment with RBC-C (ranitidine bismuth citrate 400 mg plus clarithromycin 500 mg) or OCA (omezaprole 20 mg, clarithromycin 500 mg and amoxicillin 1000 mg), given twice a day for seven days. Treatment allocation was randomly assigned.H pyloriinfection was confirmed by positive13C-urea breath test (13C-UBT).H pyloristatus was reassessed by UBT at least four and 12 weeks after treatment (negative: δ13CO2below 3.5 per mil). Intention-to-treat (ITT) eradication rates were determined for all patients with confirmedH pyloriinfection. Per protocol (PP) rate was determined for all patients treated with at least two evaluable follow-up visits.RESULTS: Three hundred five patients were included in the ITT and 222 in the PP analysis. The ITT eradication rates were 66% for RBC-C and 78% for OCA. The PP success rates were 84% for RBC-C and 96% for OCA. The difference for both ITT 12% (95% CI 2 to 22) and PP 12% (95% CI 4 to 19) were statistically significant, P=0.030 and P=0.007, respectively. Treatment was generally well tolerated.CONCLUSION: The eradication rate for the seven-day dual RBC-C regimen was lower than that for OCA.

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Effect of manual therapy in patients with hemophilia and ankle arthropathy: a randomized clinical trial

Clinical Rehabilitation ◽

10.1177/0269215519879212 ◽

2019 ◽

Vol 34 (1) ◽

pp. 111-119 ◽

Cited By ~ 1

Author(s):

Elena Donoso-Úbeda ◽

Javier Meroño-Gallut ◽

José Antonio López-Pina ◽

Rubén Cuesta-Barriuso

Keyword(s):

Manual Therapy ◽

Joint Pain ◽

Controlled Trial ◽

Control Group ◽

Load Bearing ◽

Intention To Treat ◽

Joint Health ◽

Experimental Group ◽

Treat Analysis

Objective: The aim of this study was to evaluate the effects of a manual therapy using fascial therapy on joint bleeding, joint pain and joint function in patients with hemophilic ankle arthropathy. Setting: Hemophilia patient associations. Design: Randomized, controlled trial, multicenter and intention-to-treat analysis. Participants: A total of 65 patients with hemophilic ankle arthropathy. Intervention: The experimental group ( n = 33) received one fascial therapy session per week for three weeks. The control group ( n = 32) received no treatment. Outcome measure: The primary outcome was frequency of joint bleeding measured using self-reporting. Secondary outcomes were joint pain (under load-bearing and non-load-bearing conditions) measured using the visual analog scale; joint condition was measured using the Hemophilia Joint Health Score. Outcomes were measured at baseline, posttreatment and after five months of follow-up. Results: Improvements in the frequency joint bleeding at T0, T1 and T2 were significantly higher in the experimental group (T0: mean (SD) = 1.56 (1.30); T1: mean (SD) = 0.00 (0.00); T2: mean (SD) = 0.27 (0.57)) compared to the control group (T0: mean (SD) = 1.70 (1.78); T1: mean (SD) = 0.05 (0.21); T2: mean (SD) = 0.58 (0.85)). Mean improvement of joint state after the study period was 1.74 points (±1.66) for patients in the experimental group, while the control group exhibited a joint deterioration with 0.43 points (±0.85). Ankle joint pain under load-bearing and non-load-bearing conditions improved in the experimental group with −1.72 (±1.86) and −0.50 (±1.39) points, respectively. Conclusion: The study showed that fascial therapy is favorable for patients with hemophilic ankle arthropathy.

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Virological and Clinical Outcome of DAA Containing Regimens in a Cohort of Patients in Calabria Region (Southern Italy)

Medicina ◽

10.3390/medicina56030101 ◽

2020 ◽

Vol 56 (3) ◽

pp. 101

Author(s):

Vincenzo Scaglione ◽

Maria Mazzitelli ◽

Chiara Costa ◽

Vincenzo Pisani ◽

Giuseppe Greco ◽

...

Keyword(s):

Southern Italy ◽

Liver Stiffness ◽

Age Group ◽

Intention To Treat ◽

Liver Decompensation ◽

End Of Treatment ◽

History Of ◽

Lost To Follow Up ◽

Treat Analysis

Background and objectives: In Italy, Hepatitis C Virus (HCV) infections are most prevalent in people older than 50 years of age, who often experience multi-morbidities, take co-medications, and have a long history of liver disease. These characteristics could potentially affect tolerability of HCV treatments and adherence in this subgroup. After achievement of sustained virological response (SVR), retention into care is very important both to detect the onset of possible complications and prevent further infections. In this study, SVR rates and retention into care of patients treated with directly acting antivirals (DAAs) of a single-center cohort in Southern Italy were evaluated. Materials and Methods: Patients treated with directly acting antivirals from 2014 to 2018 were included. Patients were stratified by age (i.e., <65 vs. ≥65 years) and by cirrhosis presence (i.e., liver stiffness >14.6 KPa or clinical/ultrasound cirrhosis vs. absence of these criteria). Primary outcome was availability of SVR at Weeks 12–24 after the end of treatment. Inter- and intra-group comparisons were performed along the follow-up for significant laboratory parameters. Results: In total, 212 patients were treated; 184 (87%) obtained SVR after the first treatment course and 4 patients after retreatment. Twenty-two (10.4%) patients were lost to follow-up before assessment of SVR, and two patients died before the end of treatment for liver decompensation. Considering only the first treatment episode, per protocol analysis (i.e., excluding patients lost to follow-up) showed the following rates of SVR: 97% (overall), 97% (older age group), 96% (age group <65 years), 94% (cirrhotics), and 100% (non-cirrhotics). By contrast, at the intention to treat analysis (i.e., patients lost were computed as failures), SVR percentages were significantly lower for patients <65 years of age (80%) and for non-cirrhotics (85%). Conclusions: High rates of SVR were obtained. However, younger patients and those without cirrhosis displayed an apparent high risk of being lost to follow-up. This may have important implications: since those who are lost may transmit HCV in case SVR is not achieved, these subpopulations should receive appropriate counselling during treatment.

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Effect of calcitonin gene-related peptide (-receptor) antibodies in chronic cluster headache: Results from a retrospective case series support individual treatment attempts

Cephalalgia ◽

10.1177/0333102420949866 ◽

2020 ◽

Vol 40 (14) ◽

pp. 1574-1584 ◽

Cited By ~ 1

Author(s):

Ruth Ruscheweyh ◽

Gregor Broessner ◽

Gudrun Goßrau ◽

Katja Heinze-Kuhn ◽

Tim P Jürgens ◽

...

Keyword(s):

Cluster Headache ◽

Calcitonin Gene Related Peptide ◽

Chronic Cluster Headache ◽

Individual Treatment ◽

Attack Frequency ◽

Peptide Receptor ◽

Related Peptide ◽

Calcitonin Gene ◽

Receptor Antibodies ◽

Headache Patients

Objective To assess the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor in chronic cluster headache (CCH) treatment under real world conditions. Background Calcitonin gene-related peptide has an important pathophysiological role in cluster headache. Although the randomised controlled trial with the calcitonin gene-related peptide antibody galcanezumab was negative, chronic cluster headache patients with insufficient response to other preventive treatments have been receiving individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies. Methods Data from 22 chronic cluster headache patients who received at least one dose of a calcitonin gene-related peptide(-receptor) antibody and recorded attack frequency in a headache diary were retrospectively collected at eight headache centres. Results The number of previous preventive therapies was 6.5 ± 2.4 (mean ± standard deviation, range: 2–11). The average number of attacks per week was 23.3 ± 16.4 at baseline and significantly decreased by −9.2 ± 9.7 in the first month of treatment with a calcitonin gene-related peptide(-receptor) antibody ( p < 0.001). Fifty-five percent of the patients were 50% responders and 36% were 75% responders with respect to attack frequency. Significant reduction of attack frequency started at week 1 (−6.8 ± 2.8 attacks, p < 0.01). Results were corroborated by significant decreases in weekly uses of acute headache medication (−9.8 ± 7.6, p < 0.001) and pain intensity during attacks (−1.2 ± 2.0, numerical rating scale (NRS) [0–10], p < 0.01) in the first month. In months 2 (n = 14) and 3 (n = 10), reduction of attack frequency from baseline was −8.0 ± 8.4 ( p = 0.004) and −9.1 ± 10.0 ( p = 0.024), respectively. Conclusion Under real-world conditions, individual treatment with calcitonin gene-related peptide(-receptor) antibodies was effective in 55% of our chronic cluster headache patients. This finding supports individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies in chronic cluster headache patients insufficiently responding to other therapies.

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