Dr. Charles is Clinical Associate Professor Neurology, Rutgers–New Jersey Medical School, Newark, NJ; Neurology Attending, Holy Name Medical Center, Teaneck, NJ (jacharlesmd@gmail.com).

Dr. Gallo is Interventional Radiology Attending, Holy Name Medical Center, Teaneck, NJ (Vgallo83@gmail.com).

DISCLOSURES

The authors have no financial relationships to disclose relevant to the manuscript. There was no sponsorship of, or funding for, the study.

Dr. Charles designed and conceptualized the study; analyzed study data and performed the statistical analysis; and drafted the manuscript for intellectual content. Dr. Gallo had a major role in the acquisition of interventional sphenopalatine ganglion data.

ABSTRACT

Objective

Chronic refractory migraine patients who failed repetitive dihydroergotamine/dopamine infusion protocols and conventional preventives were treated with repeated low-dose ketamine-based parenteral protocols, followed by memantine-based preventive therapy, and observed for immediate reduction in pain intensity and headache frequency.

Methods

Ten patients were treated at an outpatient infusion center for 2 to 5 sequential days with AM and PM courses of intravenous diphenhydramine, prochlorperazine, and dihydroergotamine. A daily sphenopalatine ganglion block and low-dose intramuscular ketamine were given midday between treatments, with dexamethasone given on the last infusion day. The Numeric Pain Rating Scale was measured after infusion. Carryover effect was assessed 1 month and 2 months after infusion by headache frequency while being treated with memantine and various other preventive and abortive therapies.

Results

Reduction in headache pain of 71% was achieved at the end of the infusion period. Sedation was the only adverse effect. Decreased headache frequency persisted beyond the infusion period, with an 88.6% reduction in headache days per month at 1 month and a 79.4% reduction in headache days per month at 2 months, without adverse effects.

Conclusions

Data indicate that 1) repetitive low-dose, ketamine-based parenteral therapy, followed by memantine-based preventive therapy, reduced refractory headache pain and 2) the decremental effect on headache frequency persisted beyond the infusion period. Our results support the hypothesis that multimechanistic therapies might be better than single-modality treatment. More studies, with a larger patient population, are needed to confirm whether these multimodality ketamine/memantine therapies should become the preferred approach for these extremely disabled patients.

Chronic refractory migraine (CRM) degrades function and quality of life despite elimination of triggers and adequate trials of acute and preventive medicines that have established efficacy. This definition requires that patients with chronic migraine fail adequate trials of preventive drugs, alone or in combination, in at least 2 of 4 drug classes, including beta blockers, anticonvulsants, tricyclic antidepressants, onabotulinumtoxin A, and calcium-channel blockers. Patients must also fail adequate trials of abortive medicines, including both a triptan and dihydroergotamine (DHE), intranasal or injectable formulation, and either a nonsteroidal anti-inflammatory drug or a combination analgesic, unless contraindicated.^1-4

In 1986, Raskin published a nonrandomized, nonblinded study of 2 treatments for intractable migraine in which repetitive inpatient intravenous (IV) DHE, administered in the hospital, was statistically more effective than IV diazepam in terminating cycles of intractable migraine.⁵ Most headache specialists have adopted the so-called Raskin protocol, as originally described or in any of several variations, as cornerstone therapy for CRM, chronic migraine, and prolonged status migrainosus.⁶ However, DHE-based infusion protocols do not always effectively reset the brain’s pain modulatory pathways in chronic migraine immediately posttreatment and might not induce a meaningful carryover effect.

We present 10 patients with CRM who met criteria for refractory migraine, including failure to terminate their headache with repetitive DHE/prochlorperazine/diphenhydramine/ketorolac/dexamethasone IV protocols, with or without sporadic administration of a sphenopalatine ganglion block. We treated these patients multimechanistically with repetitive IV DHE, a dopamine antagonist, an antihistamine, sphenopalatine ganglion (SPG) block, and low-dose ketamine, plus last-infusion-day dexamethasone, followed by outpatient oral memantine. Subsequently, we observed them for 2 months.

Ketamine is a phencyclidine derivative introduced the early 1960s as an IV anesthetic. Low-dose ketamine has been used successfully in the treatment of chronic pain. Today, increased interest in the application of low-dose ketamine includes cancer pain; treatment and prevention of acute and chronic pain, with and without neuropathic analgesia; fibromyalgia; complex regional pain; and migraine.^7,8 The effectiveness of ketamine in different pain disorders may arise through different pathways and/or by way of activity at various receptor systems. Effects arise predominantly by noncompetitive antagonism of the glutamate N-methyl-D-aspartate (NMDA ) receptor.^7,8

Memantine also is an NMDA receptor antagonist that is used effectively as an oral agent in CRM.⁹

METHODS

Patients enrolled in this prospective study had CRM for periods ranging from 1 to 2 years. All had daily headache that could not be terminated with repetitive DHE/prochlorperazine/diphenhydramine/ketorolac/dexamethasone IV protocols with or without sporadic administration of an SPG block. Age ranged from 18 and 68 years; all patients were female. Patients were excluded if they had known coronary artery disease, uncontrolled hypertension, or peripheral arterial disease; a history of stroke, transient ischemic attack, or pregnancy; impaired liver or renal function; smoked a tobacco product; or were taking a protease inhibitor or macrolide antibiotic.

 Approval by the institutional review board was unnecessary because all drugs and procedures are FDA-approved and have published evidence-based efficacy for migraine and other diseases.

 The Numeric Pain Rating Scale (NPRS; a scale of 0 to 10) was utilized to rate the intensity of pain from the beginning of the infusion to the end of the multiday infusion protocol, when the catheter was removed. All patients but 1 were treated for 5 days; for the 1 exception, treatment was terminated after 48 hours because of a scheduling conflict. The observational follow‐up periods for assessment of outcomes were 1 month and 2 months post-infusion.

Patients started the study with a baseline NPRS of 9 or 10. They were treated at the institution’s headache outpatient infusion center. In the morning, patients received, by sequential IV infusion, diphenhydramine, 50 mg; prochlorperazine, 10 mg; and DHE, 1 mg. They then received a midday SPG block under fluoroscopic guidance and ketamine, 0.45 mg/kg intramuscularly (IM), given in the post-anesthesia care unit. In the late afternoon, the patients received diphenhydramine, 50 mg; prochlorperazine, 10 mg; and DHE, 0.5 mg, in the Headache Outpatient Infusion Center. Patients were discharged to home by 6 PM. They received IV dexamethasone, 20 mg, on the last day of therapy.

Oral preventive agents were continued and abortives were temporarily discontinued during infusion therapy. Oral memantine was used immediately before, during, and, in all cases, after infusion, at a daily dosage that ranged from 10 mg BID to 28 mg, once-daily extended release.

RESULTS

Therapies were well-tolerated by all patients. On the last day of treatment, the entire cohort (N = 10) demonstrated an average of 71% (mean standard deviation [SD], 10.1%) reduction in pain intensity. The average reduction in headache days per month at 1 month was 88.6% (mean SD, 6.24%) and at 2 months was 79.4% (mean SD, 17.13%) (Table). Adverse effects were mild temporary sedation from ketamine. Pulse oximetry revealed no abnormal decrease in O₂ saturation. All patients reported marked overall reduction in headache disability at the end of the infusion protocol. Self-administered abortive therapies posttreatment were more efficacious than they were pretreatment. All patients indicated less headache disability overall by the end of the 2-month observation period.
 

Table. Chronic Refractory Migraine Baseline Data and Treatment Results^a

^aAll patients had daily headache at initiation of treatment.

^bHeadache days/month.

NPRS, Numeric Pain Rating Scale.

DISCUSSION

In our study of 10 patients with CRM who had daily headache treated repetitively in an outpatient infusion center with multimodality therapies, including sub-anesthetic doses of ketamine, all patients experienced marked reduction in headache pain intensity, with a whole-group average reduction of 71% by the end of infusion treatment. During post-infusion observation, all patients continued various preventive therapies, including memantine. At 1 month, the average reduction in headache frequency was 88.6%. Two months post-infusion, the average reduction in headache frequency was 79.4%. Adverse effects were minimal. Overall, the treatment was found to be safe and efficacious. All patients felt less headache disability after 2 months.

Because the protocol was administered comfortably in the Headache Outpatient Infusion Center, the inconvenience and higher cost of inpatient parenteral treatment were avoided. Ketamine, 0.45 mg/kg IM is a sub-anesthetic dose with proven efficacy in treating migraine without adverse effects in an outpatient setting.⁸ Low-dose ketamine obviated the need for anesthesia personnel and precautions. Temporary sedation was the only adverse effect. Ketamine was administered by a nurse in the post-anesthesia care unit while patients were under observation with conventional measurement of vital signs and pulse oximetry. Memantine, also an NMDA receptor antagonist, is postulated to prolong the NMDA antagonism of ketamine.

Inpatient and outpatient continuous IV DHE and repetitive IV DHE, often combined with dopamine antagonists in controlled and comparator studies, have demonstrated equal effectiveness for the treatment of chronic migraine.^5,10,11 Our patients failed these therapies. This raises the question: Should our combined multimodality, ketamine-based approach be standard parenteral therapy for CRM?

In a recent study of continuous inpatient single-modality IV ketamine, a less-impressive carryover effect was obtained, with 23% to 50% 1-month sustained responders.¹² Multimechanistic treatment superiority over monotherapy is legendary in the treatment of cancer and human immunodeficiency infection. Sumatriptan plus naproxen sodium as a single tablet for acute treatment of migraine resulted in more favorable clinical benefit compared with either monotherapy, with an acceptable, well-tolerated adverse effect profile. Because multiple pathogenic mechanisms putatively are involved in generation of the migraine symptom complex, multimechanism-targeted therapy may confer advantages over individual monotherapy. Drugs in 2 classes of migraine pharmacotherapy—triptans and nonsteroidal anti-inflammatory drugs —target distinct aspects of the vascular and inflammatory processes hypothesized to underlie migraine.¹³

Although combination therapy for CRM has not been systematically studied in randomized trials, clinical experience suggests that a rational approach to CRM treatment, utilizing a combination of treatments, may be effective when monotherapy has failed.¹⁴ During the infusion protocol, we re-set the trigeminovascular pain pathways 1) by repetitively blocking NMDA receptors (with ketamine), dopamine receptors (with prochlorperazine), and histamine receptors (with diphenhydramine); 2) by lidocaine anesthetic block of the sphenopalatine ganglia; and, on the last day of the protocol, 3) administering 1 large dose of IV dexamethasone to help prevent recurrence.¹⁵ NMDA blockade continued with oral outpatient memantine.

Virtually all patients were taking other preventives during the pretreatment period and 2-month observation period, including topiramate, venlafaxine, beta blockers, candesartan, zonisamide, onabotulinumtoxin A, neuromodulation (Cefaly Technology), and transcranial magnetic stimulation (springTMS®). Self-administered abortives were more effective in the 2-month observational period; these included IM/IV DHE; oral, spray, and subcutaneous triptans; IM ketorolac; diclofenac buffered solution; and transcranial magnetic stimulation (springTMS®). The cornerstone strategy of our treatment group that was a constant was the use of low-dose IM sub-anesthetic ketamine at a dosage of 0.45 mg/kg/d and the use of oral memantine during the follow-up observation period, at dosages ranging from 10 mg BID to 28 mg, once-daily extended release.

Limitations of this study design are:

• lack of a control group
• lack of subject randomization for comparative outcomes
• patients remaining on a variety of prophylactic regimens
• patients permitted to take any rescue therapy.

 The effect of repetitive SPG block cannot be teased out of the efficacy data, but many of our patients had a poor or temporary response to infrequent sporadic SPG blocks prior to participating in our protocol.

Many migraineurs who seek care in a headache clinic are refractory to treatment, despite advances in headache therapy; refractory migraine was found in 5.1% of these patients.¹⁶ In this small series of patients, we demonstrated immediate relief and a significant 2-month carryover effect with our multimodality parenteral protocol. Larger, controlled studies are needed to further explore this protocol with repetitive DHE, diphenhydramine, prochlorperazine, SPG block, and low-dose IM ketamine, followed by outpatient memantine. Such studies would determine whether our protocol should be utilized as a primary treatment, instead of the conventional DHE-based Raskin and modified Raskin protocols.

Although this is a small series of patients, lack of adverse effects and impressive results should give credence to utilizing our protocol as treatment for this extremely debilitated, often desperate subset of headache patients. Data indicate that, whereas ketamine combined with other therapies immediately reduced refractory headache pain, the ameliorating effect of ketamine on CRM headache frequency and pain in our protocol persisted beyond the infusion period. This phenomenon indicates a disease-modulating role for ketamine in refractory migraine pain, possibly by means of desensitization of NMDA receptors in the trigeminal nucleus caudalis—desensitization that continued with the NMDA receptor antagonist memantine and/or restoration of inhibitory sensory control in the brain.

CONCLUSION

Our results support the hypothesis that multimechanistic therapies, including low-dose IM ketamine and memantine, might be better than single-modality treatment in this debilitated, refractory population. Future studies, with larger patient populations, are needed to confirm whether these multimodality ketamine/memantine-inclusive therapies should become the preferred approach for these extremely disabled patients.

REFERENCES

1. Goadsby PJ, Schoenen J, Ferrari MD, Silberstein SD, Dodick DW. Towards a definition of intractable headache for use in clinical practice and trials. Cephalalgia. 2006;26(9):1168-1170.
2. Schulman EA, Lipton R, Peterlin BL, Levin M, Grosberg BM. Commentary from the Refractory Headache Special Interest Section on defining the pharmacologically intractable headache for clinical trials and clinical practice. Headache. 2010;50(10):1637-1639.
3. Martelletti P, Jensen RH, Antal A, et al. Neuromodulation of chronic headaches: position statement from the European Headache Federation. J Headache Pain. 2013;14:86.
4. Dodick DW, Turkel CC, DeGryse RE, et al; PREEMPT Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache. 2010;50(6):921-936.
5. Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine. Neurology. 1986;36(7):995‐997.
6. Charles JA, von Dohln P. Outpatient home-based continuous intravenous dihydroergotamine therapy for intractable migraine. Headache. 2010;50(5):852-860.
7. Sigtermans M, Noppers I, Sarton E, et al. An observational study on the effect of S+-ketamine on chronic pain versus experimental acute pain in complex regional pain syndrome type 1 patients. Eur J Pain. 2010;14(3):302-307.
8. Krusz J, Cagle J, Hall S. Intramuscular (IM) ketamine for treating headache and pain flare-ups in the clinic. J Pain. 2008;9(4):30.
9. Bigal M Rapoport A, Sheftell F, Tepper D, Tepper S. Memantine in the preventive treatment of refractory migraine. Headache. 2008;48(9):1337-1342.
10. Ford RG, Ford KT. Continuous intravenous dihydroergotamine for treatment of intractable headache. Headache. 1997;37(3):129‐136.
11. Boudreau G, Aghai E, Marchand L, Langlois M. Outpatient intravenous dihydroergotamine for probable medication overuse headache. Headache Care. 2006;3(1):45‐49.
12. Pomeroy JL, Marmura MJ, Nahas SJ, Viscusi ER. Ketamine infusions for treatment refractory headache. Headache. 2017;57(2):276-282.
13. Brandes JL, Kudrow D, Stark SR, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007;297(13):1443-1454.
14. Peterlin BL, Calhoun AH, Siegel S, Mathew NT. Rational combination therapy in refractory migraine. Headache. 2008;48(6):805-819.
15. Innes G, Macphail I, Dillon EC, Metcalfe C, Gao M. Dexamethasone prevents relapse after emergency department treatment of acute migraine: a randomized clinical trial. CJEM. 2015;1(1):26-33.
16. Irimia P, Palma JA, Fernandez-Torron R, Martinez-Vila E. Refractory migraine in a headache clinic population. BMC Neurol. 2011;11:94.

Dr. Charles is Clinical Associate Professor Neurology, Rutgers–New Jersey Medical School, Newark, NJ; Neurology Attending, Holy Name Medical Center, Teaneck, NJ (jacharlesmd@gmail.com).

Dr. Gallo is Interventional Radiology Attending, Holy Name Medical Center, Teaneck, NJ (Vgallo83@gmail.com).

DISCLOSURES

The authors have no financial relationships to disclose relevant to the manuscript. There was no sponsorship of, or funding for, the study.

Dr. Charles designed and conceptualized the study; analyzed study data and performed the statistical analysis; and drafted the manuscript for intellectual content. Dr. Gallo had a major role in the acquisition of interventional sphenopalatine ganglion data.

ABSTRACT

Objective

Chronic refractory migraine patients who failed repetitive dihydroergotamine/dopamine infusion protocols and conventional preventives were treated with repeated low-dose ketamine-based parenteral protocols, followed by memantine-based preventive therapy, and observed for immediate reduction in pain intensity and headache frequency.

Methods

Ten patients were treated at an outpatient infusion center for 2 to 5 sequential days with AM and PM courses of intravenous diphenhydramine, prochlorperazine, and dihydroergotamine. A daily sphenopalatine ganglion block and low-dose intramuscular ketamine were given midday between treatments, with dexamethasone given on the last infusion day. The Numeric Pain Rating Scale was measured after infusion. Carryover effect was assessed 1 month and 2 months after infusion by headache frequency while being treated with memantine and various other preventive and abortive therapies.

Results

Reduction in headache pain of 71% was achieved at the end of the infusion period. Sedation was the only adverse effect. Decreased headache frequency persisted beyond the infusion period, with an 88.6% reduction in headache days per month at 1 month and a 79.4% reduction in headache days per month at 2 months, without adverse effects.

Conclusions

Data indicate that 1) repetitive low-dose, ketamine-based parenteral therapy, followed by memantine-based preventive therapy, reduced refractory headache pain and 2) the decremental effect on headache frequency persisted beyond the infusion period. Our results support the hypothesis that multimechanistic therapies might be better than single-modality treatment. More studies, with a larger patient population, are needed to confirm whether these multimodality ketamine/memantine therapies should become the preferred approach for these extremely disabled patients.

Chronic refractory migraine (CRM) degrades function and quality of life despite elimination of triggers and adequate trials of acute and preventive medicines that have established efficacy. This definition requires that patients with chronic migraine fail adequate trials of preventive drugs, alone or in combination, in at least 2 of 4 drug classes, including beta blockers, anticonvulsants, tricyclic antidepressants, onabotulinumtoxin A, and calcium-channel blockers. Patients must also fail adequate trials of abortive medicines, including both a triptan and dihydroergotamine (DHE), intranasal or injectable formulation, and either a nonsteroidal anti-inflammatory drug or a combination analgesic, unless contraindicated.^1-4

In 1986, Raskin published a nonrandomized, nonblinded study of 2 treatments for intractable migraine in which repetitive inpatient intravenous (IV) DHE, administered in the hospital, was statistically more effective than IV diazepam in terminating cycles of intractable migraine.⁵ Most headache specialists have adopted the so-called Raskin protocol, as originally described or in any of several variations, as cornerstone therapy for CRM, chronic migraine, and prolonged status migrainosus.⁶ However, DHE-based infusion protocols do not always effectively reset the brain’s pain modulatory pathways in chronic migraine immediately posttreatment and might not induce a meaningful carryover effect.

We present 10 patients with CRM who met criteria for refractory migraine, including failure to terminate their headache with repetitive DHE/prochlorperazine/diphenhydramine/ketorolac/dexamethasone IV protocols, with or without sporadic administration of a sphenopalatine ganglion block. We treated these patients multimechanistically with repetitive IV DHE, a dopamine antagonist, an antihistamine, sphenopalatine ganglion (SPG) block, and low-dose ketamine, plus last-infusion-day dexamethasone, followed by outpatient oral memantine. Subsequently, we observed them for 2 months.

Ketamine is a phencyclidine derivative introduced the early 1960s as an IV anesthetic. Low-dose ketamine has been used successfully in the treatment of chronic pain. Today, increased interest in the application of low-dose ketamine includes cancer pain; treatment and prevention of acute and chronic pain, with and without neuropathic analgesia; fibromyalgia; complex regional pain; and migraine.^7,8 The effectiveness of ketamine in different pain disorders may arise through different pathways and/or by way of activity at various receptor systems. Effects arise predominantly by noncompetitive antagonism of the glutamate N-methyl-D-aspartate (NMDA ) receptor.^7,8

Memantine also is an NMDA receptor antagonist that is used effectively as an oral agent in CRM.⁹

METHODS

Patients enrolled in this prospective study had CRM for periods ranging from 1 to 2 years. All had daily headache that could not be terminated with repetitive DHE/prochlorperazine/diphenhydramine/ketorolac/dexamethasone IV protocols with or without sporadic administration of an SPG block. Age ranged from 18 and 68 years; all patients were female. Patients were excluded if they had known coronary artery disease, uncontrolled hypertension, or peripheral arterial disease; a history of stroke, transient ischemic attack, or pregnancy; impaired liver or renal function; smoked a tobacco product; or were taking a protease inhibitor or macrolide antibiotic.

 Approval by the institutional review board was unnecessary because all drugs and procedures are FDA-approved and have published evidence-based efficacy for migraine and other diseases.

 The Numeric Pain Rating Scale (NPRS; a scale of 0 to 10) was utilized to rate the intensity of pain from the beginning of the infusion to the end of the multiday infusion protocol, when the catheter was removed. All patients but 1 were treated for 5 days; for the 1 exception, treatment was terminated after 48 hours because of a scheduling conflict. The observational follow‐up periods for assessment of outcomes were 1 month and 2 months post-infusion.

Patients started the study with a baseline NPRS of 9 or 10. They were treated at the institution’s headache outpatient infusion center. In the morning, patients received, by sequential IV infusion, diphenhydramine, 50 mg; prochlorperazine, 10 mg; and DHE, 1 mg. They then received a midday SPG block under fluoroscopic guidance and ketamine, 0.45 mg/kg intramuscularly (IM), given in the post-anesthesia care unit. In the late afternoon, the patients received diphenhydramine, 50 mg; prochlorperazine, 10 mg; and DHE, 0.5 mg, in the Headache Outpatient Infusion Center. Patients were discharged to home by 6 PM. They received IV dexamethasone, 20 mg, on the last day of therapy.

Oral preventive agents were continued and abortives were temporarily discontinued during infusion therapy. Oral memantine was used immediately before, during, and, in all cases, after infusion, at a daily dosage that ranged from 10 mg BID to 28 mg, once-daily extended release.

RESULTS

Therapies were well-tolerated by all patients. On the last day of treatment, the entire cohort (N = 10) demonstrated an average of 71% (mean standard deviation [SD], 10.1%) reduction in pain intensity. The average reduction in headache days per month at 1 month was 88.6% (mean SD, 6.24%) and at 2 months was 79.4% (mean SD, 17.13%) (Table). Adverse effects were mild temporary sedation from ketamine. Pulse oximetry revealed no abnormal decrease in O₂ saturation. All patients reported marked overall reduction in headache disability at the end of the infusion protocol. Self-administered abortive therapies posttreatment were more efficacious than they were pretreatment. All patients indicated less headache disability overall by the end of the 2-month observation period.
 

Table. Chronic Refractory Migraine Baseline Data and Treatment Results^a

^aAll patients had daily headache at initiation of treatment.

^bHeadache days/month.

NPRS, Numeric Pain Rating Scale.

DISCUSSION

In our study of 10 patients with CRM who had daily headache treated repetitively in an outpatient infusion center with multimodality therapies, including sub-anesthetic doses of ketamine, all patients experienced marked reduction in headache pain intensity, with a whole-group average reduction of 71% by the end of infusion treatment. During post-infusion observation, all patients continued various preventive therapies, including memantine. At 1 month, the average reduction in headache frequency was 88.6%. Two months post-infusion, the average reduction in headache frequency was 79.4%. Adverse effects were minimal. Overall, the treatment was found to be safe and efficacious. All patients felt less headache disability after 2 months.

Because the protocol was administered comfortably in the Headache Outpatient Infusion Center, the inconvenience and higher cost of inpatient parenteral treatment were avoided. Ketamine, 0.45 mg/kg IM is a sub-anesthetic dose with proven efficacy in treating migraine without adverse effects in an outpatient setting.⁸ Low-dose ketamine obviated the need for anesthesia personnel and precautions. Temporary sedation was the only adverse effect. Ketamine was administered by a nurse in the post-anesthesia care unit while patients were under observation with conventional measurement of vital signs and pulse oximetry. Memantine, also an NMDA receptor antagonist, is postulated to prolong the NMDA antagonism of ketamine.

Inpatient and outpatient continuous IV DHE and repetitive IV DHE, often combined with dopamine antagonists in controlled and comparator studies, have demonstrated equal effectiveness for the treatment of chronic migraine.^5,10,11 Our patients failed these therapies. This raises the question: Should our combined multimodality, ketamine-based approach be standard parenteral therapy for CRM?

In a recent study of continuous inpatient single-modality IV ketamine, a less-impressive carryover effect was obtained, with 23% to 50% 1-month sustained responders.¹² Multimechanistic treatment superiority over monotherapy is legendary in the treatment of cancer and human immunodeficiency infection. Sumatriptan plus naproxen sodium as a single tablet for acute treatment of migraine resulted in more favorable clinical benefit compared with either monotherapy, with an acceptable, well-tolerated adverse effect profile. Because multiple pathogenic mechanisms putatively are involved in generation of the migraine symptom complex, multimechanism-targeted therapy may confer advantages over individual monotherapy. Drugs in 2 classes of migraine pharmacotherapy—triptans and nonsteroidal anti-inflammatory drugs —target distinct aspects of the vascular and inflammatory processes hypothesized to underlie migraine.¹³

Although combination therapy for CRM has not been systematically studied in randomized trials, clinical experience suggests that a rational approach to CRM treatment, utilizing a combination of treatments, may be effective when monotherapy has failed.¹⁴ During the infusion protocol, we re-set the trigeminovascular pain pathways 1) by repetitively blocking NMDA receptors (with ketamine), dopamine receptors (with prochlorperazine), and histamine receptors (with diphenhydramine); 2) by lidocaine anesthetic block of the sphenopalatine ganglia; and, on the last day of the protocol, 3) administering 1 large dose of IV dexamethasone to help prevent recurrence.¹⁵ NMDA blockade continued with oral outpatient memantine.

Virtually all patients were taking other preventives during the pretreatment period and 2-month observation period, including topiramate, venlafaxine, beta blockers, candesartan, zonisamide, onabotulinumtoxin A, neuromodulation (Cefaly Technology), and transcranial magnetic stimulation (springTMS®). Self-administered abortives were more effective in the 2-month observational period; these included IM/IV DHE; oral, spray, and subcutaneous triptans; IM ketorolac; diclofenac buffered solution; and transcranial magnetic stimulation (springTMS®). The cornerstone strategy of our treatment group that was a constant was the use of low-dose IM sub-anesthetic ketamine at a dosage of 0.45 mg/kg/d and the use of oral memantine during the follow-up observation period, at dosages ranging from 10 mg BID to 28 mg, once-daily extended release.

Limitations of this study design are:

• lack of a control group
• lack of subject randomization for comparative outcomes
• patients remaining on a variety of prophylactic regimens
• patients permitted to take any rescue therapy.

 The effect of repetitive SPG block cannot be teased out of the efficacy data, but many of our patients had a poor or temporary response to infrequent sporadic SPG blocks prior to participating in our protocol.

Many migraineurs who seek care in a headache clinic are refractory to treatment, despite advances in headache therapy; refractory migraine was found in 5.1% of these patients.¹⁶ In this small series of patients, we demonstrated immediate relief and a significant 2-month carryover effect with our multimodality parenteral protocol. Larger, controlled studies are needed to further explore this protocol with repetitive DHE, diphenhydramine, prochlorperazine, SPG block, and low-dose IM ketamine, followed by outpatient memantine. Such studies would determine whether our protocol should be utilized as a primary treatment, instead of the conventional DHE-based Raskin and modified Raskin protocols.

Although this is a small series of patients, lack of adverse effects and impressive results should give credence to utilizing our protocol as treatment for this extremely debilitated, often desperate subset of headache patients. Data indicate that, whereas ketamine combined with other therapies immediately reduced refractory headache pain, the ameliorating effect of ketamine on CRM headache frequency and pain in our protocol persisted beyond the infusion period. This phenomenon indicates a disease-modulating role for ketamine in refractory migraine pain, possibly by means of desensitization of NMDA receptors in the trigeminal nucleus caudalis—desensitization that continued with the NMDA receptor antagonist memantine and/or restoration of inhibitory sensory control in the brain.

CONCLUSION

Our results support the hypothesis that multimechanistic therapies, including low-dose IM ketamine and memantine, might be better than single-modality treatment in this debilitated, refractory population. Future studies, with larger patient populations, are needed to confirm whether these multimodality ketamine/memantine-inclusive therapies should become the preferred approach for these extremely disabled patients.

REFERENCES

1. Goadsby PJ, Schoenen J, Ferrari MD, Silberstein SD, Dodick DW. Towards a definition of intractable headache for use in clinical practice and trials. Cephalalgia. 2006;26(9):1168-1170.
2. Schulman EA, Lipton R, Peterlin BL, Levin M, Grosberg BM. Commentary from the Refractory Headache Special Interest Section on defining the pharmacologically intractable headache for clinical trials and clinical practice. Headache. 2010;50(10):1637-1639.
3. Martelletti P, Jensen RH, Antal A, et al. Neuromodulation of chronic headaches: position statement from the European Headache Federation. J Headache Pain. 2013;14:86.
4. Dodick DW, Turkel CC, DeGryse RE, et al; PREEMPT Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache. 2010;50(6):921-936.
5. Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine. Neurology. 1986;36(7):995‐997.
6. Charles JA, von Dohln P. Outpatient home-based continuous intravenous dihydroergotamine therapy for intractable migraine. Headache. 2010;50(5):852-860.
7. Sigtermans M, Noppers I, Sarton E, et al. An observational study on the effect of S+-ketamine on chronic pain versus experimental acute pain in complex regional pain syndrome type 1 patients. Eur J Pain. 2010;14(3):302-307.
8. Krusz J, Cagle J, Hall S. Intramuscular (IM) ketamine for treating headache and pain flare-ups in the clinic. J Pain. 2008;9(4):30.
9. Bigal M Rapoport A, Sheftell F, Tepper D, Tepper S. Memantine in the preventive treatment of refractory migraine. Headache. 2008;48(9):1337-1342.
10. Ford RG, Ford KT. Continuous intravenous dihydroergotamine for treatment of intractable headache. Headache. 1997;37(3):129‐136.
11. Boudreau G, Aghai E, Marchand L, Langlois M. Outpatient intravenous dihydroergotamine for probable medication overuse headache. Headache Care. 2006;3(1):45‐49.
12. Pomeroy JL, Marmura MJ, Nahas SJ, Viscusi ER. Ketamine infusions for treatment refractory headache. Headache. 2017;57(2):276-282.
13. Brandes JL, Kudrow D, Stark SR, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007;297(13):1443-1454.
14. Peterlin BL, Calhoun AH, Siegel S, Mathew NT. Rational combination therapy in refractory migraine. Headache. 2008;48(6):805-819.
15. Innes G, Macphail I, Dillon EC, Metcalfe C, Gao M. Dexamethasone prevents relapse after emergency department treatment of acute migraine: a randomized clinical trial. CJEM. 2015;1(1):26-33.
16. Irimia P, Palma JA, Fernandez-Torron R, Martinez-Vila E. Refractory migraine in a headache clinic population. BMC Neurol. 2011;11:94.

Dr. Charles is Clinical Associate Professor Neurology, Rutgers–New Jersey Medical School, Newark, NJ; Neurology Attending, Holy Name Medical Center, Teaneck, NJ (jacharlesmd@gmail.com).

Dr. Gallo is Interventional Radiology Attending, Holy Name Medical Center, Teaneck, NJ (Vgallo83@gmail.com).

DISCLOSURES

The authors have no financial relationships to disclose relevant to the manuscript. There was no sponsorship of, or funding for, the study.

Dr. Charles designed and conceptualized the study; analyzed study data and performed the statistical analysis; and drafted the manuscript for intellectual content. Dr. Gallo had a major role in the acquisition of interventional sphenopalatine ganglion data.

ABSTRACT

Objective

Chronic refractory migraine patients who failed repetitive dihydroergotamine/dopamine infusion protocols and conventional preventives were treated with repeated low-dose ketamine-based parenteral protocols, followed by memantine-based preventive therapy, and observed for immediate reduction in pain intensity and headache frequency.

Methods

Ten patients were treated at an outpatient infusion center for 2 to 5 sequential days with AM and PM courses of intravenous diphenhydramine, prochlorperazine, and dihydroergotamine. A daily sphenopalatine ganglion block and low-dose intramuscular ketamine were given midday between treatments, with dexamethasone given on the last infusion day. The Numeric Pain Rating Scale was measured after infusion. Carryover effect was assessed 1 month and 2 months after infusion by headache frequency while being treated with memantine and various other preventive and abortive therapies.

Results

Reduction in headache pain of 71% was achieved at the end of the infusion period. Sedation was the only adverse effect. Decreased headache frequency persisted beyond the infusion period, with an 88.6% reduction in headache days per month at 1 month and a 79.4% reduction in headache days per month at 2 months, without adverse effects.

Conclusions

Data indicate that 1) repetitive low-dose, ketamine-based parenteral therapy, followed by memantine-based preventive therapy, reduced refractory headache pain and 2) the decremental effect on headache frequency persisted beyond the infusion period. Our results support the hypothesis that multimechanistic therapies might be better than single-modality treatment. More studies, with a larger patient population, are needed to confirm whether these multimodality ketamine/memantine therapies should become the preferred approach for these extremely disabled patients.

Chronic refractory migraine (CRM) degrades function and quality of life despite elimination of triggers and adequate trials of acute and preventive medicines that have established efficacy. This definition requires that patients with chronic migraine fail adequate trials of preventive drugs, alone or in combination, in at least 2 of 4 drug classes, including beta blockers, anticonvulsants, tricyclic antidepressants, onabotulinumtoxin A, and calcium-channel blockers. Patients must also fail adequate trials of abortive medicines, including both a triptan and dihydroergotamine (DHE), intranasal or injectable formulation, and either a nonsteroidal anti-inflammatory drug or a combination analgesic, unless contraindicated.^1-4

In 1986, Raskin published a nonrandomized, nonblinded study of 2 treatments for intractable migraine in which repetitive inpatient intravenous (IV) DHE, administered in the hospital, was statistically more effective than IV diazepam in terminating cycles of intractable migraine.⁵ Most headache specialists have adopted the so-called Raskin protocol, as originally described or in any of several variations, as cornerstone therapy for CRM, chronic migraine, and prolonged status migrainosus.⁶ However, DHE-based infusion protocols do not always effectively reset the brain’s pain modulatory pathways in chronic migraine immediately posttreatment and might not induce a meaningful carryover effect.

We present 10 patients with CRM who met criteria for refractory migraine, including failure to terminate their headache with repetitive DHE/prochlorperazine/diphenhydramine/ketorolac/dexamethasone IV protocols, with or without sporadic administration of a sphenopalatine ganglion block. We treated these patients multimechanistically with repetitive IV DHE, a dopamine antagonist, an antihistamine, sphenopalatine ganglion (SPG) block, and low-dose ketamine, plus last-infusion-day dexamethasone, followed by outpatient oral memantine. Subsequently, we observed them for 2 months.

Ketamine is a phencyclidine derivative introduced the early 1960s as an IV anesthetic. Low-dose ketamine has been used successfully in the treatment of chronic pain. Today, increased interest in the application of low-dose ketamine includes cancer pain; treatment and prevention of acute and chronic pain, with and without neuropathic analgesia; fibromyalgia; complex regional pain; and migraine.^7,8 The effectiveness of ketamine in different pain disorders may arise through different pathways and/or by way of activity at various receptor systems. Effects arise predominantly by noncompetitive antagonism of the glutamate N-methyl-D-aspartate (NMDA ) receptor.^7,8

Memantine also is an NMDA receptor antagonist that is used effectively as an oral agent in CRM.⁹

METHODS

Patients enrolled in this prospective study had CRM for periods ranging from 1 to 2 years. All had daily headache that could not be terminated with repetitive DHE/prochlorperazine/diphenhydramine/ketorolac/dexamethasone IV protocols with or without sporadic administration of an SPG block. Age ranged from 18 and 68 years; all patients were female. Patients were excluded if they had known coronary artery disease, uncontrolled hypertension, or peripheral arterial disease; a history of stroke, transient ischemic attack, or pregnancy; impaired liver or renal function; smoked a tobacco product; or were taking a protease inhibitor or macrolide antibiotic.

 Approval by the institutional review board was unnecessary because all drugs and procedures are FDA-approved and have published evidence-based efficacy for migraine and other diseases.

 The Numeric Pain Rating Scale (NPRS; a scale of 0 to 10) was utilized to rate the intensity of pain from the beginning of the infusion to the end of the multiday infusion protocol, when the catheter was removed. All patients but 1 were treated for 5 days; for the 1 exception, treatment was terminated after 48 hours because of a scheduling conflict. The observational follow‐up periods for assessment of outcomes were 1 month and 2 months post-infusion.

Patients started the study with a baseline NPRS of 9 or 10. They were treated at the institution’s headache outpatient infusion center. In the morning, patients received, by sequential IV infusion, diphenhydramine, 50 mg; prochlorperazine, 10 mg; and DHE, 1 mg. They then received a midday SPG block under fluoroscopic guidance and ketamine, 0.45 mg/kg intramuscularly (IM), given in the post-anesthesia care unit. In the late afternoon, the patients received diphenhydramine, 50 mg; prochlorperazine, 10 mg; and DHE, 0.5 mg, in the Headache Outpatient Infusion Center. Patients were discharged to home by 6 PM. They received IV dexamethasone, 20 mg, on the last day of therapy.

Oral preventive agents were continued and abortives were temporarily discontinued during infusion therapy. Oral memantine was used immediately before, during, and, in all cases, after infusion, at a daily dosage that ranged from 10 mg BID to 28 mg, once-daily extended release.

RESULTS

Therapies were well-tolerated by all patients. On the last day of treatment, the entire cohort (N = 10) demonstrated an average of 71% (mean standard deviation [SD], 10.1%) reduction in pain intensity. The average reduction in headache days per month at 1 month was 88.6% (mean SD, 6.24%) and at 2 months was 79.4% (mean SD, 17.13%) (Table). Adverse effects were mild temporary sedation from ketamine. Pulse oximetry revealed no abnormal decrease in O₂ saturation. All patients reported marked overall reduction in headache disability at the end of the infusion protocol. Self-administered abortive therapies posttreatment were more efficacious than they were pretreatment. All patients indicated less headache disability overall by the end of the 2-month observation period.
 

Table. Chronic Refractory Migraine Baseline Data and Treatment Results^a

^aAll patients had daily headache at initiation of treatment.

^bHeadache days/month.

NPRS, Numeric Pain Rating Scale.

DISCUSSION

In our study of 10 patients with CRM who had daily headache treated repetitively in an outpatient infusion center with multimodality therapies, including sub-anesthetic doses of ketamine, all patients experienced marked reduction in headache pain intensity, with a whole-group average reduction of 71% by the end of infusion treatment. During post-infusion observation, all patients continued various preventive therapies, including memantine. At 1 month, the average reduction in headache frequency was 88.6%. Two months post-infusion, the average reduction in headache frequency was 79.4%. Adverse effects were minimal. Overall, the treatment was found to be safe and efficacious. All patients felt less headache disability after 2 months.

Because the protocol was administered comfortably in the Headache Outpatient Infusion Center, the inconvenience and higher cost of inpatient parenteral treatment were avoided. Ketamine, 0.45 mg/kg IM is a sub-anesthetic dose with proven efficacy in treating migraine without adverse effects in an outpatient setting.⁸ Low-dose ketamine obviated the need for anesthesia personnel and precautions. Temporary sedation was the only adverse effect. Ketamine was administered by a nurse in the post-anesthesia care unit while patients were under observation with conventional measurement of vital signs and pulse oximetry. Memantine, also an NMDA receptor antagonist, is postulated to prolong the NMDA antagonism of ketamine.

Inpatient and outpatient continuous IV DHE and repetitive IV DHE, often combined with dopamine antagonists in controlled and comparator studies, have demonstrated equal effectiveness for the treatment of chronic migraine.^5,10,11 Our patients failed these therapies. This raises the question: Should our combined multimodality, ketamine-based approach be standard parenteral therapy for CRM?

In a recent study of continuous inpatient single-modality IV ketamine, a less-impressive carryover effect was obtained, with 23% to 50% 1-month sustained responders.¹² Multimechanistic treatment superiority over monotherapy is legendary in the treatment of cancer and human immunodeficiency infection. Sumatriptan plus naproxen sodium as a single tablet for acute treatment of migraine resulted in more favorable clinical benefit compared with either monotherapy, with an acceptable, well-tolerated adverse effect profile. Because multiple pathogenic mechanisms putatively are involved in generation of the migraine symptom complex, multimechanism-targeted therapy may confer advantages over individual monotherapy. Drugs in 2 classes of migraine pharmacotherapy—triptans and nonsteroidal anti-inflammatory drugs —target distinct aspects of the vascular and inflammatory processes hypothesized to underlie migraine.¹³

Although combination therapy for CRM has not been systematically studied in randomized trials, clinical experience suggests that a rational approach to CRM treatment, utilizing a combination of treatments, may be effective when monotherapy has failed.¹⁴ During the infusion protocol, we re-set the trigeminovascular pain pathways 1) by repetitively blocking NMDA receptors (with ketamine), dopamine receptors (with prochlorperazine), and histamine receptors (with diphenhydramine); 2) by lidocaine anesthetic block of the sphenopalatine ganglia; and, on the last day of the protocol, 3) administering 1 large dose of IV dexamethasone to help prevent recurrence.¹⁵ NMDA blockade continued with oral outpatient memantine.

Virtually all patients were taking other preventives during the pretreatment period and 2-month observation period, including topiramate, venlafaxine, beta blockers, candesartan, zonisamide, onabotulinumtoxin A, neuromodulation (Cefaly Technology), and transcranial magnetic stimulation (springTMS®). Self-administered abortives were more effective in the 2-month observational period; these included IM/IV DHE; oral, spray, and subcutaneous triptans; IM ketorolac; diclofenac buffered solution; and transcranial magnetic stimulation (springTMS®). The cornerstone strategy of our treatment group that was a constant was the use of low-dose IM sub-anesthetic ketamine at a dosage of 0.45 mg/kg/d and the use of oral memantine during the follow-up observation period, at dosages ranging from 10 mg BID to 28 mg, once-daily extended release.

Limitations of this study design are:

• lack of a control group
• lack of subject randomization for comparative outcomes
• patients remaining on a variety of prophylactic regimens
• patients permitted to take any rescue therapy.

 The effect of repetitive SPG block cannot be teased out of the efficacy data, but many of our patients had a poor or temporary response to infrequent sporadic SPG blocks prior to participating in our protocol.

Many migraineurs who seek care in a headache clinic are refractory to treatment, despite advances in headache therapy; refractory migraine was found in 5.1% of these patients.¹⁶ In this small series of patients, we demonstrated immediate relief and a significant 2-month carryover effect with our multimodality parenteral protocol. Larger, controlled studies are needed to further explore this protocol with repetitive DHE, diphenhydramine, prochlorperazine, SPG block, and low-dose IM ketamine, followed by outpatient memantine. Such studies would determine whether our protocol should be utilized as a primary treatment, instead of the conventional DHE-based Raskin and modified Raskin protocols.

Although this is a small series of patients, lack of adverse effects and impressive results should give credence to utilizing our protocol as treatment for this extremely debilitated, often desperate subset of headache patients. Data indicate that, whereas ketamine combined with other therapies immediately reduced refractory headache pain, the ameliorating effect of ketamine on CRM headache frequency and pain in our protocol persisted beyond the infusion period. This phenomenon indicates a disease-modulating role for ketamine in refractory migraine pain, possibly by means of desensitization of NMDA receptors in the trigeminal nucleus caudalis—desensitization that continued with the NMDA receptor antagonist memantine and/or restoration of inhibitory sensory control in the brain.

CONCLUSION

Our results support the hypothesis that multimechanistic therapies, including low-dose IM ketamine and memantine, might be better than single-modality treatment in this debilitated, refractory population. Future studies, with larger patient populations, are needed to confirm whether these multimodality ketamine/memantine-inclusive therapies should become the preferred approach for these extremely disabled patients.

REFERENCES

1. Goadsby PJ, Schoenen J, Ferrari MD, Silberstein SD, Dodick DW. Towards a definition of intractable headache for use in clinical practice and trials. Cephalalgia. 2006;26(9):1168-1170.
2. Schulman EA, Lipton R, Peterlin BL, Levin M, Grosberg BM. Commentary from the Refractory Headache Special Interest Section on defining the pharmacologically intractable headache for clinical trials and clinical practice. Headache. 2010;50(10):1637-1639.
3. Martelletti P, Jensen RH, Antal A, et al. Neuromodulation of chronic headaches: position statement from the European Headache Federation. J Headache Pain. 2013;14:86.
4. Dodick DW, Turkel CC, DeGryse RE, et al; PREEMPT Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache. 2010;50(6):921-936.
5. Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine. Neurology. 1986;36(7):995‐997.
6. Charles JA, von Dohln P. Outpatient home-based continuous intravenous dihydroergotamine therapy for intractable migraine. Headache. 2010;50(5):852-860.
7. Sigtermans M, Noppers I, Sarton E, et al. An observational study on the effect of S+-ketamine on chronic pain versus experimental acute pain in complex regional pain syndrome type 1 patients. Eur J Pain. 2010;14(3):302-307.
8. Krusz J, Cagle J, Hall S. Intramuscular (IM) ketamine for treating headache and pain flare-ups in the clinic. J Pain. 2008;9(4):30.
9. Bigal M Rapoport A, Sheftell F, Tepper D, Tepper S. Memantine in the preventive treatment of refractory migraine. Headache. 2008;48(9):1337-1342.
10. Ford RG, Ford KT. Continuous intravenous dihydroergotamine for treatment of intractable headache. Headache. 1997;37(3):129‐136.
11. Boudreau G, Aghai E, Marchand L, Langlois M. Outpatient intravenous dihydroergotamine for probable medication overuse headache. Headache Care. 2006;3(1):45‐49.
12. Pomeroy JL, Marmura MJ, Nahas SJ, Viscusi ER. Ketamine infusions for treatment refractory headache. Headache. 2017;57(2):276-282.
13. Brandes JL, Kudrow D, Stark SR, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007;297(13):1443-1454.
14. Peterlin BL, Calhoun AH, Siegel S, Mathew NT. Rational combination therapy in refractory migraine. Headache. 2008;48(6):805-819.
15. Innes G, Macphail I, Dillon EC, Metcalfe C, Gao M. Dexamethasone prevents relapse after emergency department treatment of acute migraine: a randomized clinical trial. CJEM. 2015;1(1):26-33.
16. Irimia P, Palma JA, Fernandez-Torron R, Martinez-Vila E. Refractory migraine in a headache clinic population. BMC Neurol. 2011;11:94.

LAKE TAHOE, CALIF. – The way Stanley Vance Jr., MD, sees it, the No. 1 priority in the care of transgender youth is respecting their gender identity.

“This can really help with rapport and also help them continue to engage with your care,” he said at the annual meeting of the Society for Pediatric Dermatology.

One of the first steps is to establish the patient’s chosen name and pronouns. “Ask, use, and be consistent,” said Dr. Vance, an adolescent medicine specialist at the University of California, San Francisco. “Taking it to another level, you can implement system-level tools to ensure that all of your staff consistently use the chosen name and pronouns. Something we’ve found helpful is including questions about chosen name and pronouns on patient intake forms, and working with the IT department to have a place in our electronic medical record to put the chosen name and preferred pronouns.”

In a study published in the Journal of Adolescent Health, researchers found that the use of chosen names and pronouns for transgender use was associated with reduced depressive symptoms, suicidal ideation, and suicidal behavior among transgender youth.

Dr. Vance, who also holds a staff position at the UCSF Child and Adolescent Clinic, went on to discuss dermatologic considerations for gender diverse youth. In transgender females, estrogens can reduce the quantity and density of body and facial hair, “but it doesn’t necessarily get rid of the hair, so we may refer to dermatology for hair removal or hair reduction. There can also be a decrease in sebum production, which can lead to dry skin for those who are at risk.”

Transgender females often seek laser hair removal or electrolysis to aid in “blendability,” or how they perceive as being female or feminine. “We know that this can help in psychosocial outcomes for these young people,” Dr. Vance said. “Another reason why hair reduction and removal may be important is preoperatively for vaginoplasty.”

In transgender males, testosterone increases male pattern hair growth and can increase male pattern hair loss. “Minoxidil does not interact with gender-affirming hormone treatment. If finasteride needs to be considered, it may interfere with the development of secondary sex characteristics.” Testosterone also increases sebum production and can increase acne, particularly in the first 6 months to 1 year after initiation, and with increased titration. “Some transmasculine youth may need oral isotretinoin, as stopping testosterone can be psychologically damaging,” Dr. Vance said.

“Unfortunately, the iPLEDGE program requirements can be perceived as gender nonaffirming, because patients must register by the sex assigned to them at birth, they must take pregnancy tests, and there can be provider assumptions about sexuality which does not equate with gender identity.”

He recommended having “open and honest” conversations with patients about the requirements and limitations of dispensing oral isotretinoin. “Assure the patient that you will be respectful and affirming of their gender identity while they’re in your office,” Dr. Vance advised. “If the patient has a mental health provider, you can strategize with them to reduce gender dysphoria around this process. Finally, advocating to change the system can not only be helpful for the patient in front of you, but for other patients who are in the same situation.”

He concluded his presentation by describing transgender youth as “some of the most resilient young people I’ve had the pleasure of working with.

“I think that we can all work to make sure they feel supported in who they are,” he said.

Dr. Vance reported having no relevant financial disclosures.

dbrunk@mdedge.com

LAKE TAHOE, CALIF. – The way Stanley Vance Jr., MD, sees it, the No. 1 priority in the care of transgender youth is respecting their gender identity.

“This can really help with rapport and also help them continue to engage with your care,” he said at the annual meeting of the Society for Pediatric Dermatology.

One of the first steps is to establish the patient’s chosen name and pronouns. “Ask, use, and be consistent,” said Dr. Vance, an adolescent medicine specialist at the University of California, San Francisco. “Taking it to another level, you can implement system-level tools to ensure that all of your staff consistently use the chosen name and pronouns. Something we’ve found helpful is including questions about chosen name and pronouns on patient intake forms, and working with the IT department to have a place in our electronic medical record to put the chosen name and preferred pronouns.”

In a study published in the Journal of Adolescent Health, researchers found that the use of chosen names and pronouns for transgender use was associated with reduced depressive symptoms, suicidal ideation, and suicidal behavior among transgender youth.

Dr. Vance, who also holds a staff position at the UCSF Child and Adolescent Clinic, went on to discuss dermatologic considerations for gender diverse youth. In transgender females, estrogens can reduce the quantity and density of body and facial hair, “but it doesn’t necessarily get rid of the hair, so we may refer to dermatology for hair removal or hair reduction. There can also be a decrease in sebum production, which can lead to dry skin for those who are at risk.”

Transgender females often seek laser hair removal or electrolysis to aid in “blendability,” or how they perceive as being female or feminine. “We know that this can help in psychosocial outcomes for these young people,” Dr. Vance said. “Another reason why hair reduction and removal may be important is preoperatively for vaginoplasty.”

In transgender males, testosterone increases male pattern hair growth and can increase male pattern hair loss. “Minoxidil does not interact with gender-affirming hormone treatment. If finasteride needs to be considered, it may interfere with the development of secondary sex characteristics.” Testosterone also increases sebum production and can increase acne, particularly in the first 6 months to 1 year after initiation, and with increased titration. “Some transmasculine youth may need oral isotretinoin, as stopping testosterone can be psychologically damaging,” Dr. Vance said.

“Unfortunately, the iPLEDGE program requirements can be perceived as gender nonaffirming, because patients must register by the sex assigned to them at birth, they must take pregnancy tests, and there can be provider assumptions about sexuality which does not equate with gender identity.”

He recommended having “open and honest” conversations with patients about the requirements and limitations of dispensing oral isotretinoin. “Assure the patient that you will be respectful and affirming of their gender identity while they’re in your office,” Dr. Vance advised. “If the patient has a mental health provider, you can strategize with them to reduce gender dysphoria around this process. Finally, advocating to change the system can not only be helpful for the patient in front of you, but for other patients who are in the same situation.”

He concluded his presentation by describing transgender youth as “some of the most resilient young people I’ve had the pleasure of working with.

“I think that we can all work to make sure they feel supported in who they are,” he said.

Dr. Vance reported having no relevant financial disclosures.

dbrunk@mdedge.com

LAKE TAHOE, CALIF. – The way Stanley Vance Jr., MD, sees it, the No. 1 priority in the care of transgender youth is respecting their gender identity.

“This can really help with rapport and also help them continue to engage with your care,” he said at the annual meeting of the Society for Pediatric Dermatology.

One of the first steps is to establish the patient’s chosen name and pronouns. “Ask, use, and be consistent,” said Dr. Vance, an adolescent medicine specialist at the University of California, San Francisco. “Taking it to another level, you can implement system-level tools to ensure that all of your staff consistently use the chosen name and pronouns. Something we’ve found helpful is including questions about chosen name and pronouns on patient intake forms, and working with the IT department to have a place in our electronic medical record to put the chosen name and preferred pronouns.”

In a study published in the Journal of Adolescent Health, researchers found that the use of chosen names and pronouns for transgender use was associated with reduced depressive symptoms, suicidal ideation, and suicidal behavior among transgender youth.

Dr. Vance, who also holds a staff position at the UCSF Child and Adolescent Clinic, went on to discuss dermatologic considerations for gender diverse youth. In transgender females, estrogens can reduce the quantity and density of body and facial hair, “but it doesn’t necessarily get rid of the hair, so we may refer to dermatology for hair removal or hair reduction. There can also be a decrease in sebum production, which can lead to dry skin for those who are at risk.”

Transgender females often seek laser hair removal or electrolysis to aid in “blendability,” or how they perceive as being female or feminine. “We know that this can help in psychosocial outcomes for these young people,” Dr. Vance said. “Another reason why hair reduction and removal may be important is preoperatively for vaginoplasty.”

In transgender males, testosterone increases male pattern hair growth and can increase male pattern hair loss. “Minoxidil does not interact with gender-affirming hormone treatment. If finasteride needs to be considered, it may interfere with the development of secondary sex characteristics.” Testosterone also increases sebum production and can increase acne, particularly in the first 6 months to 1 year after initiation, and with increased titration. “Some transmasculine youth may need oral isotretinoin, as stopping testosterone can be psychologically damaging,” Dr. Vance said.

“Unfortunately, the iPLEDGE program requirements can be perceived as gender nonaffirming, because patients must register by the sex assigned to them at birth, they must take pregnancy tests, and there can be provider assumptions about sexuality which does not equate with gender identity.”

He recommended having “open and honest” conversations with patients about the requirements and limitations of dispensing oral isotretinoin. “Assure the patient that you will be respectful and affirming of their gender identity while they’re in your office,” Dr. Vance advised. “If the patient has a mental health provider, you can strategize with them to reduce gender dysphoria around this process. Finally, advocating to change the system can not only be helpful for the patient in front of you, but for other patients who are in the same situation.”

He concluded his presentation by describing transgender youth as “some of the most resilient young people I’ve had the pleasure of working with.

“I think that we can all work to make sure they feel supported in who they are,” he said.

Dr. Vance reported having no relevant financial disclosures.

dbrunk@mdedge.com

Current migraine forecasting models represent an important first step in accurately predicting future headache activity, according to a recent investigation. However, to utilize these models in a preemptive treatment paradigm where the risk of headache is treated prior to the actual experience of pain, these models must achieve greater precision with good calibration and generate predictions that are clinically actionable by individuals in their real-time home environments.

A substantial pool of candidate migraine trigger factors could be considered in the creation of forecasting models. However, since mechanistic information about causal factors that precede a migraine attack is not well understood, and such factors are difficult to measure, empirical models that are based on trigger factors that are merely associated with the onset of headache activity are likely to be the focus of forecasting efforts. Of such factors, stress has considerable empirical support and has been used to successfully forecast future headache attacks within individuals over time. At present, however, existing models possess only modest levels of discrimination and lack strong resolution in generated predictions.

Curr Pain Headache Rep. Forecasting migraine attacks and the utility of identifying triggers. 2018;22:62. doi:10.1007/s11916-018-0715-3.

Current migraine forecasting models represent an important first step in accurately predicting future headache activity, according to a recent investigation. However, to utilize these models in a preemptive treatment paradigm where the risk of headache is treated prior to the actual experience of pain, these models must achieve greater precision with good calibration and generate predictions that are clinically actionable by individuals in their real-time home environments.

A substantial pool of candidate migraine trigger factors could be considered in the creation of forecasting models. However, since mechanistic information about causal factors that precede a migraine attack is not well understood, and such factors are difficult to measure, empirical models that are based on trigger factors that are merely associated with the onset of headache activity are likely to be the focus of forecasting efforts. Of such factors, stress has considerable empirical support and has been used to successfully forecast future headache attacks within individuals over time. At present, however, existing models possess only modest levels of discrimination and lack strong resolution in generated predictions.

Curr Pain Headache Rep. Forecasting migraine attacks and the utility of identifying triggers. 2018;22:62. doi:10.1007/s11916-018-0715-3.

Current migraine forecasting models represent an important first step in accurately predicting future headache activity, according to a recent investigation. However, to utilize these models in a preemptive treatment paradigm where the risk of headache is treated prior to the actual experience of pain, these models must achieve greater precision with good calibration and generate predictions that are clinically actionable by individuals in their real-time home environments.

A substantial pool of candidate migraine trigger factors could be considered in the creation of forecasting models. However, since mechanistic information about causal factors that precede a migraine attack is not well understood, and such factors are difficult to measure, empirical models that are based on trigger factors that are merely associated with the onset of headache activity are likely to be the focus of forecasting efforts. Of such factors, stress has considerable empirical support and has been used to successfully forecast future headache attacks within individuals over time. At present, however, existing models possess only modest levels of discrimination and lack strong resolution in generated predictions.

Curr Pain Headache Rep. Forecasting migraine attacks and the utility of identifying triggers. 2018;22:62. doi:10.1007/s11916-018-0715-3.

Although unilateral pain location can be helpful in making a migraine diagnosis, it does not appear to have additional clinical implications, according to a recent study. Additionally, its absence does not rule out a diagnosis of migraine since more than half of migraineurs have bilateral head pain. Medical record information was extracted for 477 randomly selected patients with migraine seen in 2011 in a tertiary headache clinic. This included demographic data, pain location, handedness, comorbid psychiatric diagnoses, medical and emergency department visits, and use of selected headache medications. Researchers found:

• Of 477 patients, 228 (47.8%) reported lateralized pain, of which 107 (47.9%) patients were right-sided compared with 65 (28.5%) left-sided patients, while 56 (24.5%) reported unilateral pain with no side predominance.
• Contrary to expectations, with the exception of self-reported posttraumatic stress disorder, there were no statistically significant differences between left and right in measures of psychiatric distress, emergency department visits, or healthcare use.

Migraine pain location and measures of healthcare use and distress: An observational study. Pain Res Manag. 2018;6157982. doi:10.1155/2018/6157982.

Although unilateral pain location can be helpful in making a migraine diagnosis, it does not appear to have additional clinical implications, according to a recent study. Additionally, its absence does not rule out a diagnosis of migraine since more than half of migraineurs have bilateral head pain. Medical record information was extracted for 477 randomly selected patients with migraine seen in 2011 in a tertiary headache clinic. This included demographic data, pain location, handedness, comorbid psychiatric diagnoses, medical and emergency department visits, and use of selected headache medications. Researchers found:

• Of 477 patients, 228 (47.8%) reported lateralized pain, of which 107 (47.9%) patients were right-sided compared with 65 (28.5%) left-sided patients, while 56 (24.5%) reported unilateral pain with no side predominance.
• Contrary to expectations, with the exception of self-reported posttraumatic stress disorder, there were no statistically significant differences between left and right in measures of psychiatric distress, emergency department visits, or healthcare use.

Migraine pain location and measures of healthcare use and distress: An observational study. Pain Res Manag. 2018;6157982. doi:10.1155/2018/6157982.

Although unilateral pain location can be helpful in making a migraine diagnosis, it does not appear to have additional clinical implications, according to a recent study. Additionally, its absence does not rule out a diagnosis of migraine since more than half of migraineurs have bilateral head pain. Medical record information was extracted for 477 randomly selected patients with migraine seen in 2011 in a tertiary headache clinic. This included demographic data, pain location, handedness, comorbid psychiatric diagnoses, medical and emergency department visits, and use of selected headache medications. Researchers found:

• Of 477 patients, 228 (47.8%) reported lateralized pain, of which 107 (47.9%) patients were right-sided compared with 65 (28.5%) left-sided patients, while 56 (24.5%) reported unilateral pain with no side predominance.
• Contrary to expectations, with the exception of self-reported posttraumatic stress disorder, there were no statistically significant differences between left and right in measures of psychiatric distress, emergency department visits, or healthcare use.

Migraine pain location and measures of healthcare use and distress: An observational study. Pain Res Manag. 2018;6157982. doi:10.1155/2018/6157982.

A recent study found a much higher prevalence of vestibular migraine (VM) in the United States than previously reported. These results, therefore, indicate a likely under-diagnosis of VM. Researchers evaluated the responses of participants (n=21,781) in the 2008 National Health Interview Survey (NHIS) balance and dizziness supplement, which were analyzed using statistical software. They found:

• The 1-year prevalence of a dizziness or balance problem in the United States was 11.9% (2490 respondents).
• Of respondents with dizziness, 584 (23.4%) met the case definition of VM, which represents a prevalence of VM in 2.7% of adults.
• There was a female preponderance (64.1%) and a slightly younger mean age (40.9 years) for those with VM as compared with all respondents (51.7% females and 46 years, respectively).
• Multivariate analysis showed that age <40, female sex, anxiety, depression, and prior head trauma were all associated with significantly increased odds of experiencing VM.
• Only 10% of subjects meeting criteria for VM were told that migraine was the cause of their dizziness.

The epidemiology of vestibular migraine: A population-based survey study. [Published online ahead of print July 16, 2018]. Otol Neurotol. doi:10.1097/MAO.0000000000001900.

A recent study found a much higher prevalence of vestibular migraine (VM) in the United States than previously reported. These results, therefore, indicate a likely under-diagnosis of VM. Researchers evaluated the responses of participants (n=21,781) in the 2008 National Health Interview Survey (NHIS) balance and dizziness supplement, which were analyzed using statistical software. They found:

• The 1-year prevalence of a dizziness or balance problem in the United States was 11.9% (2490 respondents).
• Of respondents with dizziness, 584 (23.4%) met the case definition of VM, which represents a prevalence of VM in 2.7% of adults.
• There was a female preponderance (64.1%) and a slightly younger mean age (40.9 years) for those with VM as compared with all respondents (51.7% females and 46 years, respectively).
• Multivariate analysis showed that age <40, female sex, anxiety, depression, and prior head trauma were all associated with significantly increased odds of experiencing VM.
• Only 10% of subjects meeting criteria for VM were told that migraine was the cause of their dizziness.

The epidemiology of vestibular migraine: A population-based survey study. [Published online ahead of print July 16, 2018]. Otol Neurotol. doi:10.1097/MAO.0000000000001900.

A recent study found a much higher prevalence of vestibular migraine (VM) in the United States than previously reported. These results, therefore, indicate a likely under-diagnosis of VM. Researchers evaluated the responses of participants (n=21,781) in the 2008 National Health Interview Survey (NHIS) balance and dizziness supplement, which were analyzed using statistical software. They found:

• The 1-year prevalence of a dizziness or balance problem in the United States was 11.9% (2490 respondents).
• Of respondents with dizziness, 584 (23.4%) met the case definition of VM, which represents a prevalence of VM in 2.7% of adults.
• There was a female preponderance (64.1%) and a slightly younger mean age (40.9 years) for those with VM as compared with all respondents (51.7% females and 46 years, respectively).
• Multivariate analysis showed that age <40, female sex, anxiety, depression, and prior head trauma were all associated with significantly increased odds of experiencing VM.
• Only 10% of subjects meeting criteria for VM were told that migraine was the cause of their dizziness.

The epidemiology of vestibular migraine: A population-based survey study. [Published online ahead of print July 16, 2018]. Otol Neurotol. doi:10.1097/MAO.0000000000001900.

This marks my last editorial as medical editor of Vascular Specialist. It has been more than a privilege to have been offered this position. After all, how lucky am I to be provided with an opportunity to rant about things that annoy me or laugh in print at some of the absurdities of our professional life.

Before I put down my pen, or should I more correctly say close my word processor, I would like to add an epithet that I have yet to coin publicly. I am suggesting that we lay to rest the term “Endoleak” and replace it with “Endofill.”

At the outset, I must commend doctors White, Yu, and May for recognizing and publicizing this important potential complication of aortic endografts (White GH, Yu W, May J., J Endovasc Surg. 1996.3:124-5). However, the term “Endoleak,” which they used to describe the continuation of free-flowing blood within the aneurysm sac, has created confusion amongst nonvascular surgeons and the lay public. Often such misunderstanding has resulted in deleterious consequences. I’m sure many vascular surgeons have been summoned to the emergency room after an emergency physician incorrectly interpreted a radiologist’s report of an Endoleak as a life-threatening rupture. Others may have had to explain to a referring physician that an Endoleak does not imply the vascular surgeon had performed an inadequate procedure. Further, patients have absolutely no concept of the meaning of this term and are often frightened when they learn they have an Endoleak. So prior to consenting them for an endograft, I always bring out a plastic model of an aneurysm with an endograft in place and go through a time-consuming explanation. Seldom do they remember this account. When I see patients back who have an Endoleak, I once again find myself placating terrified individuals who think they are about to die.

So that is why we should replace the alarming “Endoleak” with the less disturbing and more descriptive “Endofill.” After all, there is no “leak” but rather a “filling” of the sac with blood. Certainly, a Type 1 “Endofill” is still dangerous, but I doubt the uninitiated would consider it an immediate problem. “Endofill” may still take some explaining, but it is less likely to cause patient anxiety or an overzealous panic in a referring physician.

Let’s face it. Even the term “leak” has led to many errors in the treatment of patients with an abdominal aortic aneurysm. For example, it is not unusual that an emergency room physician, hospitalist, or internist will triage a “leaking” aneurysm as nonurgent because it has not “ruptured.”

I think we should ban “leaking” and “leak” from the medical vernacular. Let Washington politicians use the words. Rather, vascular surgeons and radiologists should describe exactly what is happening when a limited amount of blood escapes the wall of an aneurysm by using the term “contained rupture.” I’m sure that will get the nonvascular surgeon's attention!

I’m hopeful that you will also remember some of my other epithets and aphorisms from columns. Such as “Vascular surgeons Operate, Medicate and Dilate,” that TLR (Target Lesion Revascularization) should really be “The Least Relevant.” That a nervous surgeon will not be proficient so “The most important heart in the Operating room is the surgeon’s.” That vascular surgeons are all “Knights of the rectangular table,” and that rapacious doctors are committing “White Coat Crime.” That atheroembolism to the buttocks should be called “Trash Can.” That we should always ask for long-term outcomes before accepting new technologies otherwise, we would be encouraging “Premature congratulation.” That Societies that refuse to rein in their members by refusing to use the word “inappropriate” are being “Anti-semantic.” Further, that shared decision making is essential but that “Insecurity is the price patients must pay for sharing in the decision-making process.” And, of course, my request that we all join the SOS, the “Save Our Saphenous” society.

I am also hopeful that, with time, my exhortations will aid Vascular Surgery in getting the recognition that it deserves. I have suggested many ways we can expedite this goal including possibly changing the name of the Society to The American College of Vascular Surgery and offering members the opportunity to refer to themselves as Fellows of that College. I have encouraged all who are trying to achieve a separate Residency Review Committee, and I fully support an independent American Board of Vascular Surgery.

Over the last 5 years, I have penned almost all that I believe needs to be said about vascular surgery, vascular surgeons, our patients, and the Society for Vascular Surgery. However, although my contract still allows one more year as medical editor, I felt it was time for new insights from a new generation of surgeons.

It is with great pleasure, therefore, that I pass the reins to Malachi Sheahan III, MD. Vascular Specialist has become the primary news source for our Society, and its educational articles and news items offer learning experiences not found in peer-reviewed journals. I encourage all to submit interesting news items for print, add some unusual Tips and Tricks, write letters to the editor, and tell us about your accomplishments inside and out of vascular surgery.

Please also volunteer to write Point/Counter Point articles. Vascular Specialist is your resource, and it’s not only in print but also in all forms of electronic and social media. It is up to you to make sure that it continues to thrive as a valuable resource for all our members.

I want to publicly thank the Associate Editors for their many contributions. This magazine would not be the same without their insightful comments. However, in the background is the actual “hero,” Mark Lesney. Mark has been the editor who sends Mal and me news items to review, urges us to be punctual, and is responsible for putting Vascular Specialist together. He works tirelessly under the pressure of producing a monthly periodical. Vascular Specialist is indebted to his efforts.

Finally, I want to thank you all so much for bearing with my rantings these last few years. Your letters and emails of appreciation have been an inspiration. 

This marks my last editorial as medical editor of Vascular Specialist. It has been more than a privilege to have been offered this position. After all, how lucky am I to be provided with an opportunity to rant about things that annoy me or laugh in print at some of the absurdities of our professional life.

Before I put down my pen, or should I more correctly say close my word processor, I would like to add an epithet that I have yet to coin publicly. I am suggesting that we lay to rest the term “Endoleak” and replace it with “Endofill.”

At the outset, I must commend doctors White, Yu, and May for recognizing and publicizing this important potential complication of aortic endografts (White GH, Yu W, May J., J Endovasc Surg. 1996.3:124-5). However, the term “Endoleak,” which they used to describe the continuation of free-flowing blood within the aneurysm sac, has created confusion amongst nonvascular surgeons and the lay public. Often such misunderstanding has resulted in deleterious consequences. I’m sure many vascular surgeons have been summoned to the emergency room after an emergency physician incorrectly interpreted a radiologist’s report of an Endoleak as a life-threatening rupture. Others may have had to explain to a referring physician that an Endoleak does not imply the vascular surgeon had performed an inadequate procedure. Further, patients have absolutely no concept of the meaning of this term and are often frightened when they learn they have an Endoleak. So prior to consenting them for an endograft, I always bring out a plastic model of an aneurysm with an endograft in place and go through a time-consuming explanation. Seldom do they remember this account. When I see patients back who have an Endoleak, I once again find myself placating terrified individuals who think they are about to die.

So that is why we should replace the alarming “Endoleak” with the less disturbing and more descriptive “Endofill.” After all, there is no “leak” but rather a “filling” of the sac with blood. Certainly, a Type 1 “Endofill” is still dangerous, but I doubt the uninitiated would consider it an immediate problem. “Endofill” may still take some explaining, but it is less likely to cause patient anxiety or an overzealous panic in a referring physician.

Let’s face it. Even the term “leak” has led to many errors in the treatment of patients with an abdominal aortic aneurysm. For example, it is not unusual that an emergency room physician, hospitalist, or internist will triage a “leaking” aneurysm as nonurgent because it has not “ruptured.”

I think we should ban “leaking” and “leak” from the medical vernacular. Let Washington politicians use the words. Rather, vascular surgeons and radiologists should describe exactly what is happening when a limited amount of blood escapes the wall of an aneurysm by using the term “contained rupture.” I’m sure that will get the nonvascular surgeon's attention!

I’m hopeful that you will also remember some of my other epithets and aphorisms from columns. Such as “Vascular surgeons Operate, Medicate and Dilate,” that TLR (Target Lesion Revascularization) should really be “The Least Relevant.” That a nervous surgeon will not be proficient so “The most important heart in the Operating room is the surgeon’s.” That vascular surgeons are all “Knights of the rectangular table,” and that rapacious doctors are committing “White Coat Crime.” That atheroembolism to the buttocks should be called “Trash Can.” That we should always ask for long-term outcomes before accepting new technologies otherwise, we would be encouraging “Premature congratulation.” That Societies that refuse to rein in their members by refusing to use the word “inappropriate” are being “Anti-semantic.” Further, that shared decision making is essential but that “Insecurity is the price patients must pay for sharing in the decision-making process.” And, of course, my request that we all join the SOS, the “Save Our Saphenous” society.

I am also hopeful that, with time, my exhortations will aid Vascular Surgery in getting the recognition that it deserves. I have suggested many ways we can expedite this goal including possibly changing the name of the Society to The American College of Vascular Surgery and offering members the opportunity to refer to themselves as Fellows of that College. I have encouraged all who are trying to achieve a separate Residency Review Committee, and I fully support an independent American Board of Vascular Surgery.

Over the last 5 years, I have penned almost all that I believe needs to be said about vascular surgery, vascular surgeons, our patients, and the Society for Vascular Surgery. However, although my contract still allows one more year as medical editor, I felt it was time for new insights from a new generation of surgeons.

It is with great pleasure, therefore, that I pass the reins to Malachi Sheahan III, MD. Vascular Specialist has become the primary news source for our Society, and its educational articles and news items offer learning experiences not found in peer-reviewed journals. I encourage all to submit interesting news items for print, add some unusual Tips and Tricks, write letters to the editor, and tell us about your accomplishments inside and out of vascular surgery.

Please also volunteer to write Point/Counter Point articles. Vascular Specialist is your resource, and it’s not only in print but also in all forms of electronic and social media. It is up to you to make sure that it continues to thrive as a valuable resource for all our members.

I want to publicly thank the Associate Editors for their many contributions. This magazine would not be the same without their insightful comments. However, in the background is the actual “hero,” Mark Lesney. Mark has been the editor who sends Mal and me news items to review, urges us to be punctual, and is responsible for putting Vascular Specialist together. He works tirelessly under the pressure of producing a monthly periodical. Vascular Specialist is indebted to his efforts.

Finally, I want to thank you all so much for bearing with my rantings these last few years. Your letters and emails of appreciation have been an inspiration. 

This marks my last editorial as medical editor of Vascular Specialist. It has been more than a privilege to have been offered this position. After all, how lucky am I to be provided with an opportunity to rant about things that annoy me or laugh in print at some of the absurdities of our professional life.

Before I put down my pen, or should I more correctly say close my word processor, I would like to add an epithet that I have yet to coin publicly. I am suggesting that we lay to rest the term “Endoleak” and replace it with “Endofill.”

At the outset, I must commend doctors White, Yu, and May for recognizing and publicizing this important potential complication of aortic endografts (White GH, Yu W, May J., J Endovasc Surg. 1996.3:124-5). However, the term “Endoleak,” which they used to describe the continuation of free-flowing blood within the aneurysm sac, has created confusion amongst nonvascular surgeons and the lay public. Often such misunderstanding has resulted in deleterious consequences. I’m sure many vascular surgeons have been summoned to the emergency room after an emergency physician incorrectly interpreted a radiologist’s report of an Endoleak as a life-threatening rupture. Others may have had to explain to a referring physician that an Endoleak does not imply the vascular surgeon had performed an inadequate procedure. Further, patients have absolutely no concept of the meaning of this term and are often frightened when they learn they have an Endoleak. So prior to consenting them for an endograft, I always bring out a plastic model of an aneurysm with an endograft in place and go through a time-consuming explanation. Seldom do they remember this account. When I see patients back who have an Endoleak, I once again find myself placating terrified individuals who think they are about to die.

So that is why we should replace the alarming “Endoleak” with the less disturbing and more descriptive “Endofill.” After all, there is no “leak” but rather a “filling” of the sac with blood. Certainly, a Type 1 “Endofill” is still dangerous, but I doubt the uninitiated would consider it an immediate problem. “Endofill” may still take some explaining, but it is less likely to cause patient anxiety or an overzealous panic in a referring physician.

Let’s face it. Even the term “leak” has led to many errors in the treatment of patients with an abdominal aortic aneurysm. For example, it is not unusual that an emergency room physician, hospitalist, or internist will triage a “leaking” aneurysm as nonurgent because it has not “ruptured.”

I think we should ban “leaking” and “leak” from the medical vernacular. Let Washington politicians use the words. Rather, vascular surgeons and radiologists should describe exactly what is happening when a limited amount of blood escapes the wall of an aneurysm by using the term “contained rupture.” I’m sure that will get the nonvascular surgeon's attention!

I’m hopeful that you will also remember some of my other epithets and aphorisms from columns. Such as “Vascular surgeons Operate, Medicate and Dilate,” that TLR (Target Lesion Revascularization) should really be “The Least Relevant.” That a nervous surgeon will not be proficient so “The most important heart in the Operating room is the surgeon’s.” That vascular surgeons are all “Knights of the rectangular table,” and that rapacious doctors are committing “White Coat Crime.” That atheroembolism to the buttocks should be called “Trash Can.” That we should always ask for long-term outcomes before accepting new technologies otherwise, we would be encouraging “Premature congratulation.” That Societies that refuse to rein in their members by refusing to use the word “inappropriate” are being “Anti-semantic.” Further, that shared decision making is essential but that “Insecurity is the price patients must pay for sharing in the decision-making process.” And, of course, my request that we all join the SOS, the “Save Our Saphenous” society.

I am also hopeful that, with time, my exhortations will aid Vascular Surgery in getting the recognition that it deserves. I have suggested many ways we can expedite this goal including possibly changing the name of the Society to The American College of Vascular Surgery and offering members the opportunity to refer to themselves as Fellows of that College. I have encouraged all who are trying to achieve a separate Residency Review Committee, and I fully support an independent American Board of Vascular Surgery.

Over the last 5 years, I have penned almost all that I believe needs to be said about vascular surgery, vascular surgeons, our patients, and the Society for Vascular Surgery. However, although my contract still allows one more year as medical editor, I felt it was time for new insights from a new generation of surgeons.

It is with great pleasure, therefore, that I pass the reins to Malachi Sheahan III, MD. Vascular Specialist has become the primary news source for our Society, and its educational articles and news items offer learning experiences not found in peer-reviewed journals. I encourage all to submit interesting news items for print, add some unusual Tips and Tricks, write letters to the editor, and tell us about your accomplishments inside and out of vascular surgery.

Please also volunteer to write Point/Counter Point articles. Vascular Specialist is your resource, and it’s not only in print but also in all forms of electronic and social media. It is up to you to make sure that it continues to thrive as a valuable resource for all our members.

I want to publicly thank the Associate Editors for their many contributions. This magazine would not be the same without their insightful comments. However, in the background is the actual “hero,” Mark Lesney. Mark has been the editor who sends Mal and me news items to review, urges us to be punctual, and is responsible for putting Vascular Specialist together. He works tirelessly under the pressure of producing a monthly periodical. Vascular Specialist is indebted to his efforts.

Finally, I want to thank you all so much for bearing with my rantings these last few years. Your letters and emails of appreciation have been an inspiration. 

Whether you attended VAM18 or not, if you need more meeting, we have you covered. All things VAM are available here. For example:

• Find link to CME claim info
• Watch on-site videos and enjoy slide shows
• Find a link to the full schedule, with abstracts, moderators, faculty bios, exhibitors

VAM On Demand slides and videos will soon be available for purchase; watch Pulse and/or your inbox for the announcement!

Whether you attended VAM18 or not, if you need more meeting, we have you covered. All things VAM are available here. For example:

• Find link to CME claim info
• Watch on-site videos and enjoy slide shows
• Find a link to the full schedule, with abstracts, moderators, faculty bios, exhibitors

VAM On Demand slides and videos will soon be available for purchase; watch Pulse and/or your inbox for the announcement!

Whether you attended VAM18 or not, if you need more meeting, we have you covered. All things VAM are available here. For example:

• Find link to CME claim info
• Watch on-site videos and enjoy slide shows
• Find a link to the full schedule, with abstracts, moderators, faculty bios, exhibitors

VAM On Demand slides and videos will soon be available for purchase; watch Pulse and/or your inbox for the announcement!

The deadline to submit applications for the SVS Foundation Research Career Development Travel Award is Aug. 15. This award aims to develop strong leaders in vascular surgery. Awardees are assigned an SVS research mentor and are provided with funds to attend an establish research career development course.

The deadline to submit applications for the SVS Foundation Research Career Development Travel Award is Aug. 15. This award aims to develop strong leaders in vascular surgery. Awardees are assigned an SVS research mentor and are provided with funds to attend an establish research career development course.

The deadline to submit applications for the SVS Foundation Research Career Development Travel Award is Aug. 15. This award aims to develop strong leaders in vascular surgery. Awardees are assigned an SVS research mentor and are provided with funds to attend an establish research career development course.

The deadline for applications for the SVS International Scholars Program has been extended to Sept. 1. The program provides up to four scholarships to qualified young vascular surgeons from countries other than the United States or Canada. Awardees receive $5,000 each, to attend the 2019 Vascular Annual Meeting and to visit clinical, teaching and research facilities in the U.S. and Canada. Apply today.

The deadline for applications for the SVS International Scholars Program has been extended to Sept. 1. The program provides up to four scholarships to qualified young vascular surgeons from countries other than the United States or Canada. Awardees receive $5,000 each, to attend the 2019 Vascular Annual Meeting and to visit clinical, teaching and research facilities in the U.S. and Canada. Apply today.

The deadline for applications for the SVS International Scholars Program has been extended to Sept. 1. The program provides up to four scholarships to qualified young vascular surgeons from countries other than the United States or Canada. Awardees receive $5,000 each, to attend the 2019 Vascular Annual Meeting and to visit clinical, teaching and research facilities in the U.S. and Canada. Apply today.

PCOS Update 2018
R. Mimi Secor, DNP, FNP-BC, FAANP, Nurse Practitioner Associates for Continuing Education

Polycystic ovary syndrome is the most common reproductive endocrine disorder, affecting 1 in 15 women in the United States. Secor reviewed the signs, symptoms, risk factors, and pathophysiology of the condition, as well as new research pointing toward its relationship with the gut microbiome. She also covered the work-up, differential, and considerations if pregnancy is desired. The treatment discussion included off-label use of metformin and letrozole.

Hypercalcemia/Parathyroid Disease Unraveled: 3 Cases to Consider
Ji Hyun (CJ) Chun, PA-C, MPAS, BC-ADM, American Society of Endocrine PAs

Chun reviewed the physiology of calcium homeostasis and presented a work-up plan for hypercalcemia and hyperparathyroidism. He shared the surgical criteria for parathyroidectomy, as well as nonsurgical treatment options, and discussed the development, potential consequences, and treatment of vitamin D deficiency.

Osteoporosis: Sticks and Stones May or May Not Break My Bones?
Richard S. Pope, MPAS, PA-C, DFAAPA, CPAAPA, Quinnipiac University

FRAX^® (fracture risk assessment tool), bone mineral density (BMD), vertebral fracture assessment, and trabecular bone score are all validated tools for evaluating osteoporosis, began Pope. Age and previous fractures are perhaps the strongest, independent predictors of fracture risk. Antiresorptive therapy produces a modest increase in BMD. Anabolic therapy with parathyroid hormone increases BMD more than antiresorptive treatment, but it is not yet obvious that fracture protection is greater.

Osteoporosis: Case Studies for Consideration
R. Mimi Secor, DNP, FNP-BC, FAANP, Nurse Practitioner Associates for Continuing Education, and Richard S. Pope, MPAS, PA-C, DFAAPA, CPAAPA, Quinnipiac University

How long should you treat patients with bisphosphonates? How is osteoporosis treatment best monitored? What is the best definition of successful treatment of osteoporosis? Secor and Pope answered these questions and emphasized reviewing with patients diet and lifestyle modifications and their importance to bone health. They also explained how to analyze risk factors beyond the DXA (dual-energy x-ray absorptiometry) score (eg, height loss), and how to target therapy based on co‐morbidities.

Continue to: Men's and Women's Health Issues and Endocrine Disease

Men’s and Women’s Health Issues and Endocrine Disease
Ji Hyun (CJ) Chun, PA-C, MPAS, BC-ADM, American Society of Endocrine PAs, and R. Mimi Secor, DNP, FNP-BC, FAANP, Nurse Practitioner Associates for Continuing Education

Chun and Secor reviewed the physiology and pathophysiology of male hypogonadism, the elements of a comprehensive diagnostic protocol, and appropriate monitoring of patients taking testosterone replacement therapy (TRT). They said that differentiating organic hypogonadism and late-onset hypogonadism (LOH) is of utmost importance to prevent long-term complications of true hypogonadism. While the benefits of treatment clearly outweigh the risks for patients with organic hypogonadism, the benefit-risk ratio for patients with LOH is unclear.

PCOS Update 2018
R. Mimi Secor, DNP, FNP-BC, FAANP, Nurse Practitioner Associates for Continuing Education

Polycystic ovary syndrome is the most common reproductive endocrine disorder, affecting 1 in 15 women in the United States. Secor reviewed the signs, symptoms, risk factors, and pathophysiology of the condition, as well as new research pointing toward its relationship with the gut microbiome. She also covered the work-up, differential, and considerations if pregnancy is desired. The treatment discussion included off-label use of metformin and letrozole.

Hypercalcemia/Parathyroid Disease Unraveled: 3 Cases to Consider
Ji Hyun (CJ) Chun, PA-C, MPAS, BC-ADM, American Society of Endocrine PAs

Chun reviewed the physiology of calcium homeostasis and presented a work-up plan for hypercalcemia and hyperparathyroidism. He shared the surgical criteria for parathyroidectomy, as well as nonsurgical treatment options, and discussed the development, potential consequences, and treatment of vitamin D deficiency.

Osteoporosis: Sticks and Stones May or May Not Break My Bones?
Richard S. Pope, MPAS, PA-C, DFAAPA, CPAAPA, Quinnipiac University

FRAX^® (fracture risk assessment tool), bone mineral density (BMD), vertebral fracture assessment, and trabecular bone score are all validated tools for evaluating osteoporosis, began Pope. Age and previous fractures are perhaps the strongest, independent predictors of fracture risk. Antiresorptive therapy produces a modest increase in BMD. Anabolic therapy with parathyroid hormone increases BMD more than antiresorptive treatment, but it is not yet obvious that fracture protection is greater.

Osteoporosis: Case Studies for Consideration
R. Mimi Secor, DNP, FNP-BC, FAANP, Nurse Practitioner Associates for Continuing Education, and Richard S. Pope, MPAS, PA-C, DFAAPA, CPAAPA, Quinnipiac University

How long should you treat patients with bisphosphonates? How is osteoporosis treatment best monitored? What is the best definition of successful treatment of osteoporosis? Secor and Pope answered these questions and emphasized reviewing with patients diet and lifestyle modifications and their importance to bone health. They also explained how to analyze risk factors beyond the DXA (dual-energy x-ray absorptiometry) score (eg, height loss), and how to target therapy based on co‐morbidities.

Continue to: Men's and Women's Health Issues and Endocrine Disease

Men’s and Women’s Health Issues and Endocrine Disease
Ji Hyun (CJ) Chun, PA-C, MPAS, BC-ADM, American Society of Endocrine PAs, and R. Mimi Secor, DNP, FNP-BC, FAANP, Nurse Practitioner Associates for Continuing Education

Chun and Secor reviewed the physiology and pathophysiology of male hypogonadism, the elements of a comprehensive diagnostic protocol, and appropriate monitoring of patients taking testosterone replacement therapy (TRT). They said that differentiating organic hypogonadism and late-onset hypogonadism (LOH) is of utmost importance to prevent long-term complications of true hypogonadism. While the benefits of treatment clearly outweigh the risks for patients with organic hypogonadism, the benefit-risk ratio for patients with LOH is unclear.

PCOS Update 2018
R. Mimi Secor, DNP, FNP-BC, FAANP, Nurse Practitioner Associates for Continuing Education

Polycystic ovary syndrome is the most common reproductive endocrine disorder, affecting 1 in 15 women in the United States. Secor reviewed the signs, symptoms, risk factors, and pathophysiology of the condition, as well as new research pointing toward its relationship with the gut microbiome. She also covered the work-up, differential, and considerations if pregnancy is desired. The treatment discussion included off-label use of metformin and letrozole.

Hypercalcemia/Parathyroid Disease Unraveled: 3 Cases to Consider
Ji Hyun (CJ) Chun, PA-C, MPAS, BC-ADM, American Society of Endocrine PAs

Chun reviewed the physiology of calcium homeostasis and presented a work-up plan for hypercalcemia and hyperparathyroidism. He shared the surgical criteria for parathyroidectomy, as well as nonsurgical treatment options, and discussed the development, potential consequences, and treatment of vitamin D deficiency.

Osteoporosis: Sticks and Stones May or May Not Break My Bones?
Richard S. Pope, MPAS, PA-C, DFAAPA, CPAAPA, Quinnipiac University

FRAX^® (fracture risk assessment tool), bone mineral density (BMD), vertebral fracture assessment, and trabecular bone score are all validated tools for evaluating osteoporosis, began Pope. Age and previous fractures are perhaps the strongest, independent predictors of fracture risk. Antiresorptive therapy produces a modest increase in BMD. Anabolic therapy with parathyroid hormone increases BMD more than antiresorptive treatment, but it is not yet obvious that fracture protection is greater.

Osteoporosis: Case Studies for Consideration
R. Mimi Secor, DNP, FNP-BC, FAANP, Nurse Practitioner Associates for Continuing Education, and Richard S. Pope, MPAS, PA-C, DFAAPA, CPAAPA, Quinnipiac University

How long should you treat patients with bisphosphonates? How is osteoporosis treatment best monitored? What is the best definition of successful treatment of osteoporosis? Secor and Pope answered these questions and emphasized reviewing with patients diet and lifestyle modifications and their importance to bone health. They also explained how to analyze risk factors beyond the DXA (dual-energy x-ray absorptiometry) score (eg, height loss), and how to target therapy based on co‐morbidities.

Continue to: Men's and Women's Health Issues and Endocrine Disease

Men’s and Women’s Health Issues and Endocrine Disease
Ji Hyun (CJ) Chun, PA-C, MPAS, BC-ADM, American Society of Endocrine PAs, and R. Mimi Secor, DNP, FNP-BC, FAANP, Nurse Practitioner Associates for Continuing Education

Chun and Secor reviewed the physiology and pathophysiology of male hypogonadism, the elements of a comprehensive diagnostic protocol, and appropriate monitoring of patients taking testosterone replacement therapy (TRT). They said that differentiating organic hypogonadism and late-onset hypogonadism (LOH) is of utmost importance to prevent long-term complications of true hypogonadism. While the benefits of treatment clearly outweigh the risks for patients with organic hypogonadism, the benefit-risk ratio for patients with LOH is unclear.