Single-Pulse Transcranial Magnetic Stimulation for the preventive treatment of difficult-to-treat migraine: a 12-month prospective analysis.

BACKGROUND: Initial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine. METHODS: This is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders). RESULTS: One hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3-56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0-26.0) to 13.0 days (IQR: 5.75-24.0) (P = 0.002, r = - 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75-22.0) to 9.0 (IQR: 4.0-15.25) (P = 0.002, r = - 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64-69) at baseline to 62 at month 3 (IQR: 56-65) (P < 0.001, r = - 0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity. CONCLUSIONS: This open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.

10 kHz spinal cord stimulation for the treatment of non-surgical refractory back pain: subanalysis of pooled data from two prospective studies.

Spinal cord stimulation at 10 kHz is a promising therapy for non-surgical refractory back pain; however, published data are currently limited. We present a subanalysis of prospectively collected clinical outcome data for non-surgical refractory back pain patients treated with 10 kHz spinal cord stimulation, from the independent cohorts of two previous studies (SENZA-RCT and SENZA-EU). Clinical outcomes were evaluated at pre-implantation (baseline), 3 months, 6 months and 12 months following 10 kHz spinal cord stimulator implantation. These included: pain relief; responder rate (≥ 50% pain relief from baseline); remission rate (VAS ≤ 3.0 cm); disability (Oswestry Disability Index(ODI)); and opioid use. At 3 months, average back pain decreased by 70% in the combined cohort (60% in the SENZA-RCT and 78% in the SENZA-EU cohorts). This was sustained at 12 months, with a 73% back pain responder rate and 68% remission rate in the combined cohort. Leg pain relief results were generally comparable to those for back pain relief. At 12 months, the combined cohort had an average decrease in ODI scores of 15.7% points from baseline and opioid use more than halved. In conclusion, 10 kHz spinal cord stimulation reduced pain, disability and opioid consumption in non-surgical refractory back pain subjects. Application of this therapy may improve the care of non-surgical refractory back pain patients and reduce their opioid consumption.

A prospective case series of sphenopalatine ganglion pulsed radiofrequency therapy for refractory chronic cluster headache.

BACKGROUND AND PURPOSE: The management options for chronic cluster headache (CCH) are limited and a significant proportion of patients become refractory to pharmacological treatments. Pulsed radiofrequency (PRF) of the sphenopalatine ganglion (SPG) may present an efficacious, minimally invasive treatment modality for patients with refractory CCH. We describe the clinical outcomes of 14 patients with refractory CCH treated with PRF of the SPG. METHODS: Patients with medically refractory CCH who underwent percutaneous SPG-PRF treatment between January 2016 and April 2019 were included in this report. Patients obtaining at least 30% reduction in weekly cluster attacks for at least 3 months were defined as responders. Treatment-related side effects were collected. RESULTS: A total of 14 patients were included in this report (nine males). At a median follow-up of 6.5 (range 6-13) months post-procedure, eight patients (57.1%) were defined as responders to the treatment. Six patients were non-responders and reported either a reduction in frequency and severity of attacks for <3 months (2/6), no improvement (2/6) or temporary worsening of symptoms (1/6). The majority of patients (63.6%, n = 7/11) treated with >45 V were responders compared with responders treated with 45 V (33.3%, n = 1/3). Five patients (35.7%) experienced post-procedural side effects. CONCLUSION: This case series suggests that PRF targeting the SPG might offer a safe, minimally invasive and effective treatment for medically refractory CCH. Given the small number of cases and the short follow-up, larger and more robust studies will be needed to confirm our findings.

Prospective real-world analysis of OnabotulinumtoxinA in chronic migraine post-National Institute for Health and Care Excellence UK technology appraisal.

BACKGROUND AND PURPOSE: The National Institute for Health and Care Excellence (NICE) in the UK recommends the use of OnabotulinumtoxinA (BoNTA, Botox® ) in the management of chronic migraine (CM) following specific guidelines within the National Health Service. In view of the lack of data on the efficacy of this therapy following implementation of these guidelines in clinical practice and on the evaluation of guidance compliance, we aimed to evaluate the effectiveness and safety of BoNTA in patients with CM following the NICE guidelines. METHODS: This was a prospective real-life audit study. RESULTS: After two treatments, 127 of 200 patients (63.5%) obtained at least a 30% reduction in headache days. Those who continued the treatment up to 3 years reported a stable beneficial effect compared with baseline. Amongst responders, 68 patients (53.5%) were reclassified as episodic migraineurs. A total of 57 of these patients (83.8%) converted to an episodic migraine pattern at 6-month follow-up. The majority of those whose migraine became episodic after BoNTA extended the treatment intervals beyond 3 months (range 4-8 months) before noticing any worsening of headache. We observed no significant differences in the efficacy measures in patients treated with 155 U BoNTA compared with those treated with >155 U BoNTA. CONCLUSIONS: When administered according to the NICE guidance, BoNTA produced a clinically meaningful effect in the long-term management of CM with and without medication overuse headache. Treatment discontinuation when CM becomes episodic may be useful in clinical practice to identify those who may benefit from extended treatment intervals. Our clinical experience indicates a lack of additional benefit from using the 'follow-the-pain' paradigm.

Cervical 10 kHz spinal cord stimulation in the management of chronic, medically refractory migraine: A prospective, open-label, exploratory study.

BACKGROUND: A significant minority of chronic migraine (CM) subjects fail conventional medical treatment (rCM), becoming highly disabled. Implantation of an occipital nerve stimulator is a therapeutic option for these subjects. Paresthesia-free cervical 10 kHz spinal cord stimulation (HF10 SCS) may provide an alternative. We report the results of a prospective, open-label, exploratory study assessing the long-term safety, tolerability and efficacy of cervical HF10 SCS in cohort of rCM subjects. METHODS: Included subjects were diagnosed with CM by an experienced headache specialist with the aid of an hourly headache diary. They were refractory to conventional medical treatments including onabotulinumtoxin-A injections. Medication overuse headache was not an exclusion criteria. Enrolled subjects underwent a 2- to 4-week tunnelled cervical HF10 SCS trial followed by a permanent system implant if a significant, subjective reduction in headache intensity/episodes was reported during the trial. Subjects were evaluated at baseline and 6 months after implantation with the aid of monthly diaries and headache-specific questionnaires. RESULTS: Seventeen subjects underwent a trial of cervical HF10 SCS; 14 were still implanted at 6 months (one trial failure, one trial infection, one implant site infection). Seven of the 14 subjects had >30% reduction in headache days. The average reduction in headache days was 6.9 for the overall population and 12.9 among the responders. Three subjects reported tenderness over the IPG/connection site, and one had a lead migration that required surgical revision. CONCLUSION: Paresthesia-free cervical HF10 SCS may be a safe and effective therapeutic option for chronic migraineurs refractory to conventional treatments.

Failed back surgery syndrome: who has failed?

INTRODUCTION: Failed back surgery syndrome (FBSS) results from a cascade of medical and surgical events that lead to or leave the patient with chronic back and radicular pain. This concept is extremely difficult to understand, both for the patient and for the therapist. The difficulty is related to the connotations of failure and blame directly associated with this term. The perception of the medical situation varies enormously according to the background and medical education of the clinician who manages this type of patient. Eight health system experts (2 pain physicians, 1 orthopaedic spine surgeon, 1 neuro spine surgeon, 1 functional neurosurgeon, 1 physiatrist, 1 psychologist and one health-economic expert) were asked to define and share their specialist point of view concerning the management of postoperative back and radicular pain. Ideally, it could be proposed that the patient would derive optimal benefit from systematic confrontation of these various points of view in order to propose the best treatment option at a given point in time to achieve the best possible care pathway. CONCLUSION: The initial pejorative connotation of FBSS suggesting failure or blame must now be replaced to direct the patient and therapists towards a temporal concept focusing on the future rather than the past. In addition to the redefinition of an optimised care pathway, a consensus based on consultation would allow redefinition and renaming of this syndrome in order to ensure a more positive approach centered on the patient.

Burns, endothelial dysfunction, and oxidative stress: the role of antioxidants.

Background. Burns cause a systemic inflammatory response, endothelial dysfunction, and increased microvascular permeability which results in oedema being formed; these effects are probably the result of a complex interplay between the direct effects of heat on the microcirculation and the action of chemical mediators, including reactive oxygen species. The use of antioxidants can reduce these changes, which are considered a promised step in burns management. Patients and methods. Forty-eight burn patients of either sex and with varying burns percentages were involved in the study. They were each allocated to one of four groups: A, B, C, and D, each group composed of 12 patients. Groups B, C, and D were treated with antioxidants: allopurinol, melatonin, and N-acetylcysteine respectively, while group A was treated according to normal hospital policy, without antioxidants; 12 healthy subjects (group E) served as a control group for comparison. In each group, serum malondialdehyde and serum glutathione levels were measured and liver and kidney function tests were performed, as well as microalbuminuria tests, using standard methods. Results. The administration of antioxidants to burns patients produced significant improvements in the parameters studied compared to group A parameters (no antioxidant given). Conclusion. This study clearly demonstrates the role of reactive oxygen species in endothelial dysfunction occurring in burn patients and the beneficial effect of antioxidants in reducing it, as shown by the reduced microalbuminuria and reduced resuscitation fluid in antioxidant-treated burn patients; the study also supports newly emerging evidence regarding the use of microalbuminuria as an indicator for endothelial dysfunction in burn patients.

Role of antioxidants in the treatment of burn lesions.

Burns are a major health problem worldwide, with high mortality and morbidity in addition to causing changes in the quality of life of burn patients. Utilizing antioxidant therapeutic strategies depending on new mechanisms involved in the pathogenesis of burns-related "oxidative stress" may be considered a promising step in burns management. This study involved 180 burn patients of varying age and either sex and with varying burns percentages. The patients were subdivided into six groups (A, B, C, D, E, and F); each group thus included 30 patients. Patients in groups B, C, D, E, and F were treated with antioxidants (vitamin E with vitamin C, zinc sulphate, allopurinol, melatonin, and N-acetylcysteine respectively) while group A was treated according to hospital policy, without any antioxidant; also, healthy subjects (group G) were involved in the study as a control group for comparison.In each group we examined serum malondialdehyde and serum glutathione levels, serum zinc and copper levels, liver function, renal function, mortality rate, and healing time, using standard methods. It was found that the administration of antioxidants to burn patients produced significant improvement in the parameters studied compared with group A (no antioxidant given). This study clearly shows the importance of the therapeutic targeting of oxidative stress in the treatment of burns. It is important to consider antioxidant a most effective weapon that must be added to the arsenal available in the combating of burn complications.

How to decrease the incidence of eschar formation during the use of topical povidone-iodine ointment in the treatment of burns.

The aim of this study was to prevent eschar formation in thermally injured patients during the use of povidoneiodine ointment by modifying therapeutic protocols depending on normal events in healing process. Sixty thermally injured patients of different age groups, sex, and occupation with different burn sizes were involved in the study, allocated to two groups. Group A was made up of 17 patients treated with topical povidone-iodine ointment in addition to other prescribed drugs according to the burn unit regimen, while group B was comprised of 43 patients treated with topical povidone-iodine ointment for the first four days post-injury followed by topical silver sulphadiazine cream until discharge and with other prescribed drugs according to the burn unit regimen. In both groups the following were studied, using standard methods: oxidative stress parameters; thyroid, liver, and renal function test; microbiology; mortality rate; healing time and economic aspects. It was found that treatment of burn patients with topical povidone-iodine ointment for the first four days post-injury followed by topical silver sulphadiazine cream reduced the incidence of eschar formation from 100% to 2.3%, in addition to maintaining improvement in burn outcome when using povidone-iodine ointment during the full course of treatment. It is concluded that for the modification of treatment protocols in burns designed to obtain normal wound healing and at the same time to avoid the undesirable effects of the treatment given, the use of topical povidone-iodine ointment for the first four days post-injury, followed by topical silver sulphadiazine cream, was a good application. In addition, this study clearly shows the importance of the therapeutic targeting of oxidative stress in burn treatment, especially during the first four days post-injury, a period when blood levels of oxidative stress parameters are at a maximum.

Effect of zinc supplement in the prognosis of burn patients in iraq.

Many studies have reported that zinc plasma levels significantly decrease after a burn, leading to zinc deficiency, and that increased free radical generation and decreased natural antioxidant may negatively affect wound healing and burn outcome in general. Targeting of these changes is considered an important strategy in the treatment of burns in an attempt to improve burn outcome in the clinical setting. Zinc was given orally in a nutritional dose (15 mg elemental zinc) as a zinc sulphate capsule to burn patients in order to improve post-burn zinc deficiency and burn outcome. The study was carried out in 58 burn patients of different age groups, sex, and occupation with different burn size. The patients were allocated to two groups: group A patients (43 in number) were treated with topical povidone-iodine ointment for the first four days post-injury followed by topical silver sulphadiazine cream 1% until discharge in addition to other prescribed drugs according to our burn unit policy; group B patients (15) received the same treatment as group A plus a single daily oral dose of zinc sulphate in a 66 mg capsule, equivalent to 15 mg elemental zinc. In each group, using standard methods, we considered plasma zinc and copper levels, oxidative stress parameters, thyroid, liver, and renal function tests, microbiological factors, mortality rate, healing time, and cost effectiveness. The administration of zinc in dietary doses significantly increased the plasma zinc level in burn patients to around normal control levels and improved the antioxidant status, as represented by elevation of the natural antioxidant level (glutathione), in addition to improving healing time, the incidence of eschar formation, and the mortality rate, compared with the zinc-nonsupplemented group. We conclude that dietary zinc supplementation in zinc-deficient burn patients led to great improvements in their outcome and that zinc deficiency was as an important goal to target during treatment; also, that the use of a combination of topical and systemic antioxidants (povidoneiodine ointment and zinc sulphate, respectively) represented a good strategy for improving results in burn patient treatment.

Role of the antioxidant effect of vitamin e with vitamin C and topical povidone-iodine ointment in the treatment of burns.

Objective. Burns represent a major health problem worldwide, with high mortality and morbidity and economic loss even with small burns. Changes in medical treatment protocols depending on a new mechanism involved in the pathogenicity of burns, i.e. oxidative stress (such as the use of povidone-iodine alone or in combination with vitamin E and vitamin C) may improve the outcome and reduce the economic loss. Patients and methods. Thirty-eight thermally injured patients of different age groups, sex, and occupation with different burn size, admitted to the burn unit in Baquba General Hospital, Iraq, were involved in this clinical trial. The patients were allocated to three groups: group A (8 patients), treated according to hospital policy; group B (17 patients), treated with topical povidone-iodine ointment; and group C (13 patients), treated with topical povidone-iodine ointment with systemic once daily 400 mg vitamin E and 500 mg vitamin C in addition to the classical antibiotic used by our hospital. In each group of oxidative stress parameters, the thyroid, liver, and kidney function test, microbiological studies, the mortality rate and healing time measurements, and economic studies were performed using standard methods. Results. Treatment with topical povidone-iodine ointment or in combination with systemic vitamin E and vitamin C was found to be of significant benefit in improving oxidative stress parameters, the mortality rate, healing time, and cost, and was free of any adverse thyroid, hepatic, or renal effects. Conclusion. Treatment of thermally injured patients with topical povidone-iodine ointment significantly improved oxidative stress parameters, indicating its antioxidant effect. Further investigation is needed to explain the exact mechanism by which povidone-iodine exerts this antioxidant effect. Treatment with topical povidone-iodine ointment alone or in combination with systemic vitamin E and vitamin C significantly improves the outcome of thermally injured patients in a safe way, thanks to the newly emerged mechanism - oxidative stress - involved in burns pathogenesis.

Respiratory effects of low-dose bupivacaine interscalene block.

In this double-blind study, interscalene brachial plexus (ISBP) block was performed in 11 volunteers using 10 ml of either 0.25% (n = 6) or 0.5% (n = 5) bupivacaine with epinephrine 1:200,000. Diaphragmatic excursion, respiratory function and neural function were assessed for 90 min. Our results showed that hemidiaphragmatic excursion declined significantly after block in the 0.5% group and paradoxical movement during inspiration was more common than in the 0.25% group. Forced vital capacity and forced expiratory volume in 1 s declined significantly in the 0.5% group (mean 74.6 (SD 13.0)% and 78.2 (19.9)% of baseline, respectively) but not in the 0.25% group. Sensory anaesthesia in the upper limb was found consistently in both groups, although biceps paralysis occurred earlier after 0.5% bupivacaine. We conclude that ISBP block using 10 ml of 0.25% bupivacaine provided upper limb anaesthesia to pinprick in C5-6 dermatomes with only occasional interference with respiratory function.

Analgesic effect of interscalene block using low-dose bupivacaine for outpatient arthroscopic shoulder surgery.

BACKGROUND AND OBJECTIVES: Although interscalene brachial plexus block (ISBPB) is often used to provide anesthesia for arthroscopic shoulder surgery, its selective analgesic effect, provided by low-dose local anesthetic, has not been studied. We hypothesized that ISBPB using a low volume and low concentration of bupivacaine can provide effective postoperative analgesia for shoulder surgery without producing significant sensory or motor block elsewhere. METHODS: In this double-blind study, 30 outpatients scheduled to undergo shoulder arthroscopy were randomly assigned to receive either an ISBPB with 10 mL 0.125% bupivacaine with epinephrine 1:400,000 (n = 15) or 10 mL of normal saline (n = 15). The block was performed preoperative, prior to a standardized general anesthetic. Postoperative pain scores, imorphine and oral analgesic consumption, recovery profile, and patient satisfaction were recorded. RESULTS: In the ISBPB group, verbal analog pain scores within 120 minutes after surgery were lower, morphine consumption in the postanesthesia care unit was significantly lower (2.7+/-2.6 mg vs 9.5+/-5.2 mg), the time to postoperative administration of the first systemic or oral analgesic was significantly longer (141+/-182 minutes vs 13+/-10 minutes), the degree of motor and sensory block 120 minutes after surgery was minimal, time to reach hospital discharge criteria was earlier, and patient satisfaction with postoperative analgesia at 24-hour follow-up was greater. Thirty-three percent of the patients receiving ISBPB did not require any analgesic prior to hospital discharge. CONCLUSIONS: Interscalene brachial plexus block with low-dose bupivacaine is a useful and selective analgesic technique for outpatient shoulder arthroscopic surgery.

A comparative study of low-dose hyperbaric spinal lidocaine 0.5% versus 5% for continuous spinal anesthesia.

BACKGROUND AND OBJECTIVES: Concerns of cauda equina syndrome have discouraged clinicians to use 5% lidocaine for continuous spinal anesthesia. Earlier reports indicated that single-shot spinal lidocaine 0.5% is effective for minor gynecologic and perianal surgery. In the present study, we evaluate the anesthetic and hemodynamic effects of low dose hyperbaric 0.5% lidocaine for continuous spinal anesthesia and compare with those of the 5% lidocaine solution in patients undergoing urologic surgery. METHODS: Spinal anesthesia was induced via an indwelling subarachnoid catheter in 42 elderly male patients (range, 57-84 years) undergoing transurethral prostate and bladder procedures. Patients were randomly assigned to receive an initial 30-mg bolus of hyperbaric lidocaine in the form of either 6 mL of 0.5% solution or 0.6 mL of 5% solution. Additional 30-mg boluses (to a total of 90 mg) were given, if necessary, to establish initial sensory block to T10 or higher and lower limb paralysis. Supplemental doses of 30 mg or less were given during surgery, as needed. Dermatomal level of sensory anesthesia and degree of motor blockade were assessed at regular intervals by a blinded observer. Heart rate and blood pressure (mean systolic and diastolic) values were monitored at regular intervals. RESULTS: Forty patients were studied successfully. Both hyperbaric 0.5% and 5% lidocaine provided adequate surgical anesthesia in 75% (30/40) of patients after a single 30-mg dose. A median peak sensory level of T5 (range, T2-T9) achieved within 11.1 +/- 4.5 minutes in patients receiving the 0.5% solution was significantly higher than the peak sensory level of T7 (range, T4-T12) in the 5% group (P = .043). The duration of surgical anesthesia after a 30-mg dose was similar in both groups--48.1 +/- 12.1 minutes versus 50.8 +/- 16.5 minutes respectively. Of the 30 patients (15 in each group) who received 30 mg initially, 25 required repeat lidocaine dosing through the catheter during surgery. The maximum decrease in heart rate and blood pressure values was within 10% and 20%, respectively, of baseline values in both groups. In the remaining patients (10/40), anesthesia was achieved successfully in five patients in the 0.5% group and three patients in the 5% group after two 30-mg lidocaine boluses (60 mg) and two patients in the 5% group after three 30-mg boluses (90 mg). CONCLUSIONS: Continuous spinal anesthesia produced by 0.5% lidocaine with 7.5% dextrose is as effective as that produced by the 5% lidocaine solution in elderly patients undergoing urologic surgery. An initial 30-mg bolus delivered via indwelling subarachnoid catheter was sufficient to achieve surgical anesthesia for approximately 50 minutes in most patients. Hemodynamic effects of the two lidocaine solutions were also comparable.