Headache & Migraine

Key clinical point: Real-time ultrasound-guided stellate ganglion block (SGB) can effectively ameliorate migraine pain and disability without causing any serious complications, thus improving the quality of life of patients.

Major finding: After 3 months of SGB administration, the numerical rating scale score decreased from 7.0 to 2.0 (P < .01), Migraine Disability Assessment Scale total score from 14.0 to 7.0 (P < .001), and analgesic use frequency from 6.2 ± 2.8 to 1.9 ± 1.8. No serious complications were observed.

Study details: The study enrolled 81 patients aged >18 years with migraine who received SGB on the affected side with 0.15% ropivacaine weekly 4 times.

Disclosures: The study was sponsored by a grant from the Shanghai Municipal Health Commission. The authors reported no conflicts of interest.

Source: Hou J et al. Real-time ultrasound-guided stellate ganglion block for migraine: an observational study. BMC Anesthesiol. 2022;22:78 (Mar 24). Doi: 10.1186/s12871-022-01622-8

Key clinical point: Real-time ultrasound-guided stellate ganglion block (SGB) can effectively ameliorate migraine pain and disability without causing any serious complications, thus improving the quality of life of patients.

Major finding: After 3 months of SGB administration, the numerical rating scale score decreased from 7.0 to 2.0 (P < .01), Migraine Disability Assessment Scale total score from 14.0 to 7.0 (P < .001), and analgesic use frequency from 6.2 ± 2.8 to 1.9 ± 1.8. No serious complications were observed.

Study details: The study enrolled 81 patients aged >18 years with migraine who received SGB on the affected side with 0.15% ropivacaine weekly 4 times.

Disclosures: The study was sponsored by a grant from the Shanghai Municipal Health Commission. The authors reported no conflicts of interest.

Source: Hou J et al. Real-time ultrasound-guided stellate ganglion block for migraine: an observational study. BMC Anesthesiol. 2022;22:78 (Mar 24). Doi: 10.1186/s12871-022-01622-8

Key clinical point: Real-time ultrasound-guided stellate ganglion block (SGB) can effectively ameliorate migraine pain and disability without causing any serious complications, thus improving the quality of life of patients.

Major finding: After 3 months of SGB administration, the numerical rating scale score decreased from 7.0 to 2.0 (P < .01), Migraine Disability Assessment Scale total score from 14.0 to 7.0 (P < .001), and analgesic use frequency from 6.2 ± 2.8 to 1.9 ± 1.8. No serious complications were observed.

Study details: The study enrolled 81 patients aged >18 years with migraine who received SGB on the affected side with 0.15% ropivacaine weekly 4 times.

Disclosures: The study was sponsored by a grant from the Shanghai Municipal Health Commission. The authors reported no conflicts of interest.

Source: Hou J et al. Real-time ultrasound-guided stellate ganglion block for migraine: an observational study. BMC Anesthesiol. 2022;22:78 (Mar 24). Doi: 10.1186/s12871-022-01622-8

Key clinical point: Migraine frequency decreases significantly in most patients with migraine on resuming preventive treatment with the same calcitonin gene-related peptide-receptor (CGRP-[R]) monoclonal antibody (mAb) after a 3-month drug holiday.

Major finding: After 9-12 weeks of therapy resumption, monthly migraine days reduced significantly (−4.5 days, P < .001) and attained a level comparable with that in the 4-week period before therapy discontinuation (P > .999).

Study details: Findings are from a longitudinal cohort study including 39 patients with episodic or chronic migraine who restarted treatment with erenumab (n = 16) or galcanezumab/fremanezumab (n = 23) after a 3-month drug holiday following the first treatment cycle with the same CGRP(-R) mAb.

Disclosures: This study did not receive any financial support. Some authors declared serving on the advisory board of or receiving consulting, speaker, or personal fees from various sources.

Source: Raffaelli B et al. Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: A real-world experience. J Headache Pain. 2022;23:40 (Mar 30). Doi:  10.1186/s10194-022-01417-9

Key clinical point: Migraine frequency decreases significantly in most patients with migraine on resuming preventive treatment with the same calcitonin gene-related peptide-receptor (CGRP-[R]) monoclonal antibody (mAb) after a 3-month drug holiday.

Major finding: After 9-12 weeks of therapy resumption, monthly migraine days reduced significantly (−4.5 days, P < .001) and attained a level comparable with that in the 4-week period before therapy discontinuation (P > .999).

Study details: Findings are from a longitudinal cohort study including 39 patients with episodic or chronic migraine who restarted treatment with erenumab (n = 16) or galcanezumab/fremanezumab (n = 23) after a 3-month drug holiday following the first treatment cycle with the same CGRP(-R) mAb.

Disclosures: This study did not receive any financial support. Some authors declared serving on the advisory board of or receiving consulting, speaker, or personal fees from various sources.

Source: Raffaelli B et al. Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: A real-world experience. J Headache Pain. 2022;23:40 (Mar 30). Doi:  10.1186/s10194-022-01417-9

Key clinical point: Migraine frequency decreases significantly in most patients with migraine on resuming preventive treatment with the same calcitonin gene-related peptide-receptor (CGRP-[R]) monoclonal antibody (mAb) after a 3-month drug holiday.

Major finding: After 9-12 weeks of therapy resumption, monthly migraine days reduced significantly (−4.5 days, P < .001) and attained a level comparable with that in the 4-week period before therapy discontinuation (P > .999).

Study details: Findings are from a longitudinal cohort study including 39 patients with episodic or chronic migraine who restarted treatment with erenumab (n = 16) or galcanezumab/fremanezumab (n = 23) after a 3-month drug holiday following the first treatment cycle with the same CGRP(-R) mAb.

Disclosures: This study did not receive any financial support. Some authors declared serving on the advisory board of or receiving consulting, speaker, or personal fees from various sources.

Source: Raffaelli B et al. Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: A real-world experience. J Headache Pain. 2022;23:40 (Mar 30). Doi:  10.1186/s10194-022-01417-9

Key clinical point: Topiramate in combination with monthly injections of greater occipital nerve block (GONB) is better at decreasing monthly migraine days (MMD) in chronic migraine (CM) than topiramate monotherapy at month 3 and is equally well tolerated.

Major finding: At month 3, greater reductions in MMD were observed in patients receiving topiramate and GONB with lidocaine+methylprednisolone (−9.6 vs. −7.3 days; P = .003) and topiramate and GONB with only lidocaine (−10.1 vs. −7.3 days; P < .001) compared with patients receiving topiramate monotherapy. Tolerability between the groups was comparable.

Study details: Findings are from a parallel group, three-arm study including 125 adult patients with CM who were randomly assigned to receive topiramate alone (n = 41), topiramate and GONB with lidocaine+methylprednisolone in month 1 followed by monthly lidocaine injections (n = 44), or topiramate and GONB with monthly lidocaine injections (n = 40) for 3 months.

Disclosures: The study received no financial support. The authors declared no conflicts of interest.

Source: Chowdhury D et al. Efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block versus topiramate monotherapy for the preventive treatment of chronic migraine: A randomized controlled trial. Cephalalgia. 2022 (Mar 8). Doi: 10.1177/03331024221082077

Key clinical point: Topiramate in combination with monthly injections of greater occipital nerve block (GONB) is better at decreasing monthly migraine days (MMD) in chronic migraine (CM) than topiramate monotherapy at month 3 and is equally well tolerated.

Major finding: At month 3, greater reductions in MMD were observed in patients receiving topiramate and GONB with lidocaine+methylprednisolone (−9.6 vs. −7.3 days; P = .003) and topiramate and GONB with only lidocaine (−10.1 vs. −7.3 days; P < .001) compared with patients receiving topiramate monotherapy. Tolerability between the groups was comparable.

Study details: Findings are from a parallel group, three-arm study including 125 adult patients with CM who were randomly assigned to receive topiramate alone (n = 41), topiramate and GONB with lidocaine+methylprednisolone in month 1 followed by monthly lidocaine injections (n = 44), or topiramate and GONB with monthly lidocaine injections (n = 40) for 3 months.

Disclosures: The study received no financial support. The authors declared no conflicts of interest.

Source: Chowdhury D et al. Efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block versus topiramate monotherapy for the preventive treatment of chronic migraine: A randomized controlled trial. Cephalalgia. 2022 (Mar 8). Doi: 10.1177/03331024221082077

Key clinical point: Topiramate in combination with monthly injections of greater occipital nerve block (GONB) is better at decreasing monthly migraine days (MMD) in chronic migraine (CM) than topiramate monotherapy at month 3 and is equally well tolerated.

Major finding: At month 3, greater reductions in MMD were observed in patients receiving topiramate and GONB with lidocaine+methylprednisolone (−9.6 vs. −7.3 days; P = .003) and topiramate and GONB with only lidocaine (−10.1 vs. −7.3 days; P < .001) compared with patients receiving topiramate monotherapy. Tolerability between the groups was comparable.

Study details: Findings are from a parallel group, three-arm study including 125 adult patients with CM who were randomly assigned to receive topiramate alone (n = 41), topiramate and GONB with lidocaine+methylprednisolone in month 1 followed by monthly lidocaine injections (n = 44), or topiramate and GONB with monthly lidocaine injections (n = 40) for 3 months.

Disclosures: The study received no financial support. The authors declared no conflicts of interest.

Source: Chowdhury D et al. Efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block versus topiramate monotherapy for the preventive treatment of chronic migraine: A randomized controlled trial. Cephalalgia. 2022 (Mar 8). Doi: 10.1177/03331024221082077

Key clinical point: External trigeminal nerve stimulation (e-TNS) for 2 consecutive hours is an effective, safe, nonpharmacological, and noninvasive acute treatment option for a migraine attack with or without aura.

Major finding: A significantly higher percentage of patients experienced pain freedom (25.5% vs. 18.3%; P < .05) and showed resolution of the most bothersome migraine symptoms (56.4% vs. 42.3%; P < .01) with e-TNS vs. sham treatment, effectuating a therapeutic gain of 7.2% and 14.1%, respectively.

Study details: The intention-to-treat population in this multicenter, prospective, phase 3 study, TEAM, consisted of 538 adult patients with episodic migraine with or without aura who were randomly assigned to receive active (n = 259) or sham (n = 279) stimulation for 2 hours.

Disclosures: The study was sponsored by Cefaly Technology, Belgium. Some authors reported receiving consulting fees, advisory board honoraria, or research grants from various sources. MAL Johnson is the Global Director of Medical Affairs for Cefaly.

Source: Kuruvilla DE et al. Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM). Sci Rep. 2022;12:5110 (Mar 24). Doi: 10.1038/s41598-022-09071-6

Key clinical point: External trigeminal nerve stimulation (e-TNS) for 2 consecutive hours is an effective, safe, nonpharmacological, and noninvasive acute treatment option for a migraine attack with or without aura.

Major finding: A significantly higher percentage of patients experienced pain freedom (25.5% vs. 18.3%; P < .05) and showed resolution of the most bothersome migraine symptoms (56.4% vs. 42.3%; P < .01) with e-TNS vs. sham treatment, effectuating a therapeutic gain of 7.2% and 14.1%, respectively.

Study details: The intention-to-treat population in this multicenter, prospective, phase 3 study, TEAM, consisted of 538 adult patients with episodic migraine with or without aura who were randomly assigned to receive active (n = 259) or sham (n = 279) stimulation for 2 hours.

Disclosures: The study was sponsored by Cefaly Technology, Belgium. Some authors reported receiving consulting fees, advisory board honoraria, or research grants from various sources. MAL Johnson is the Global Director of Medical Affairs for Cefaly.

Source: Kuruvilla DE et al. Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM). Sci Rep. 2022;12:5110 (Mar 24). Doi: 10.1038/s41598-022-09071-6

Key clinical point: External trigeminal nerve stimulation (e-TNS) for 2 consecutive hours is an effective, safe, nonpharmacological, and noninvasive acute treatment option for a migraine attack with or without aura.

Major finding: A significantly higher percentage of patients experienced pain freedom (25.5% vs. 18.3%; P < .05) and showed resolution of the most bothersome migraine symptoms (56.4% vs. 42.3%; P < .01) with e-TNS vs. sham treatment, effectuating a therapeutic gain of 7.2% and 14.1%, respectively.

Study details: The intention-to-treat population in this multicenter, prospective, phase 3 study, TEAM, consisted of 538 adult patients with episodic migraine with or without aura who were randomly assigned to receive active (n = 259) or sham (n = 279) stimulation for 2 hours.

Disclosures: The study was sponsored by Cefaly Technology, Belgium. Some authors reported receiving consulting fees, advisory board honoraria, or research grants from various sources. MAL Johnson is the Global Director of Medical Affairs for Cefaly.

Source: Kuruvilla DE et al. Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM). Sci Rep. 2022;12:5110 (Mar 24). Doi: 10.1038/s41598-022-09071-6

Key clinical point: Fremanezumab lowers the pain and neurological symptom days in patients with episodic migraine (EM) or chronic migraine (CM) with associated neurological dysfunction and inadequate response to 2-4 prior classes of prophylactic medications.

Major finding: Quarterly and monthly fremanezumab vs. placebo significantly reduced monthly mean days with neurological symptoms (least square mean difference −1.7 days and −1.8 days vs. −0.5 days; both P ≤ .01) and monthly migraine days (P < .0001) over 12 weeks.

Study details: This post hoc analysis included 837 patients with difficult-to-treat EM or CM from the phase 3b FOCUS study who received quarterly fremanezumab, monthly fremanezumab, or placebo over 12 weeks and were categorized into patients with (n = 493) and without (n = 344) associated neurological dysfunction.

Disclosures: This study was funded by Teva Branded Pharmaceutical Products R&D, Inc., USA. Some authors declared serving as consultants, speakers, or principal clinical trial investigators for or receiving personal fees from various sources, including Teva, and other authors are employees or stockholders of Teva.

Source: Lampl C et al. Efficacy and quality-of-life improvements with fremanezumab treatment in patients with difficult-to-treat migraine with associated neurological dysfunction. Eur J Neurol. 2022 (Mar 18). Doi: 10.1111/ene.15328

Key clinical point: Fremanezumab lowers the pain and neurological symptom days in patients with episodic migraine (EM) or chronic migraine (CM) with associated neurological dysfunction and inadequate response to 2-4 prior classes of prophylactic medications.

Major finding: Quarterly and monthly fremanezumab vs. placebo significantly reduced monthly mean days with neurological symptoms (least square mean difference −1.7 days and −1.8 days vs. −0.5 days; both P ≤ .01) and monthly migraine days (P < .0001) over 12 weeks.

Study details: This post hoc analysis included 837 patients with difficult-to-treat EM or CM from the phase 3b FOCUS study who received quarterly fremanezumab, monthly fremanezumab, or placebo over 12 weeks and were categorized into patients with (n = 493) and without (n = 344) associated neurological dysfunction.

Disclosures: This study was funded by Teva Branded Pharmaceutical Products R&D, Inc., USA. Some authors declared serving as consultants, speakers, or principal clinical trial investigators for or receiving personal fees from various sources, including Teva, and other authors are employees or stockholders of Teva.

Source: Lampl C et al. Efficacy and quality-of-life improvements with fremanezumab treatment in patients with difficult-to-treat migraine with associated neurological dysfunction. Eur J Neurol. 2022 (Mar 18). Doi: 10.1111/ene.15328

Key clinical point: Fremanezumab lowers the pain and neurological symptom days in patients with episodic migraine (EM) or chronic migraine (CM) with associated neurological dysfunction and inadequate response to 2-4 prior classes of prophylactic medications.

Major finding: Quarterly and monthly fremanezumab vs. placebo significantly reduced monthly mean days with neurological symptoms (least square mean difference −1.7 days and −1.8 days vs. −0.5 days; both P ≤ .01) and monthly migraine days (P < .0001) over 12 weeks.

Study details: This post hoc analysis included 837 patients with difficult-to-treat EM or CM from the phase 3b FOCUS study who received quarterly fremanezumab, monthly fremanezumab, or placebo over 12 weeks and were categorized into patients with (n = 493) and without (n = 344) associated neurological dysfunction.

Disclosures: This study was funded by Teva Branded Pharmaceutical Products R&D, Inc., USA. Some authors declared serving as consultants, speakers, or principal clinical trial investigators for or receiving personal fees from various sources, including Teva, and other authors are employees or stockholders of Teva.

Source: Lampl C et al. Efficacy and quality-of-life improvements with fremanezumab treatment in patients with difficult-to-treat migraine with associated neurological dysfunction. Eur J Neurol. 2022 (Mar 18). Doi: 10.1111/ene.15328

Key clinical point: Consistent with the overall study population results, eptinezumab therapy demonstrated favorable efficacy and safety in patients with episodic migraine (EM) or chronic migraine (CM) and self-reported aura from the PROMISE studies.

Major finding: Over weeks 1-12, monthly migraine days decreased with 100 mg and 300 mg eptinezumab vs. placebo in patients with EM (100 mg, −3.9 days; 300 mg, −4.2 days vs. −3.3 days) and CM (100 mg, −7.1 days; 300 mg, −7.6 days vs. −5.9 days) with aura. Treatment-emergent adverse event rates were similar across treatment groups.

Study details: Of 1741 patients with EM/CM from the PROMISE-1 and PROMISE-2 trials, this post hoc analysis included 877 patients who self-reported migraine with aura at screening and received eptinezumab (n = 583) or placebo (n = 294).

Disclosures: Lundbeck Seattle BioPharmaceuticals, Inc., USA, funded the study. Some authors declared serving as consultants, speakers, advisors, or as a primary trial investigator for and receiving personal fees and research support from various sources, including Lundbeck. Some authors are current or former employees of Lundbeck or its subsidiary company.

Source: Ashina M et al. Efficacy and safety of eptinezumab in patients with migraine and self-reported aura: Post hoc analysis of PROMISE-1 and PROMISE-2. Cephalalgia. 2022 (Mar 18). Doi: 10.1177/03331024221077646

Key clinical point: Consistent with the overall study population results, eptinezumab therapy demonstrated favorable efficacy and safety in patients with episodic migraine (EM) or chronic migraine (CM) and self-reported aura from the PROMISE studies.

Major finding: Over weeks 1-12, monthly migraine days decreased with 100 mg and 300 mg eptinezumab vs. placebo in patients with EM (100 mg, −3.9 days; 300 mg, −4.2 days vs. −3.3 days) and CM (100 mg, −7.1 days; 300 mg, −7.6 days vs. −5.9 days) with aura. Treatment-emergent adverse event rates were similar across treatment groups.

Study details: Of 1741 patients with EM/CM from the PROMISE-1 and PROMISE-2 trials, this post hoc analysis included 877 patients who self-reported migraine with aura at screening and received eptinezumab (n = 583) or placebo (n = 294).

Disclosures: Lundbeck Seattle BioPharmaceuticals, Inc., USA, funded the study. Some authors declared serving as consultants, speakers, advisors, or as a primary trial investigator for and receiving personal fees and research support from various sources, including Lundbeck. Some authors are current or former employees of Lundbeck or its subsidiary company.

Source: Ashina M et al. Efficacy and safety of eptinezumab in patients with migraine and self-reported aura: Post hoc analysis of PROMISE-1 and PROMISE-2. Cephalalgia. 2022 (Mar 18). Doi: 10.1177/03331024221077646

Key clinical point: Consistent with the overall study population results, eptinezumab therapy demonstrated favorable efficacy and safety in patients with episodic migraine (EM) or chronic migraine (CM) and self-reported aura from the PROMISE studies.

Major finding: Over weeks 1-12, monthly migraine days decreased with 100 mg and 300 mg eptinezumab vs. placebo in patients with EM (100 mg, −3.9 days; 300 mg, −4.2 days vs. −3.3 days) and CM (100 mg, −7.1 days; 300 mg, −7.6 days vs. −5.9 days) with aura. Treatment-emergent adverse event rates were similar across treatment groups.

Study details: Of 1741 patients with EM/CM from the PROMISE-1 and PROMISE-2 trials, this post hoc analysis included 877 patients who self-reported migraine with aura at screening and received eptinezumab (n = 583) or placebo (n = 294).

Disclosures: Lundbeck Seattle BioPharmaceuticals, Inc., USA, funded the study. Some authors declared serving as consultants, speakers, advisors, or as a primary trial investigator for and receiving personal fees and research support from various sources, including Lundbeck. Some authors are current or former employees of Lundbeck or its subsidiary company.

Source: Ashina M et al. Efficacy and safety of eptinezumab in patients with migraine and self-reported aura: Post hoc analysis of PROMISE-1 and PROMISE-2. Cephalalgia. 2022 (Mar 18). Doi: 10.1177/03331024221077646

Key clinical point: Galcanezumab is an effective and safe long-term treatment option for chronic migraine.

Major finding: At month 12, patients in the placebo, 120 mg galcanezumab, and 240 mg galcanezumab groups showed a mean change of −8.5, −9.0, and −8.0 days in monthly migraine days from the beginning of the double-blind period, respectively (all within-group P < .001). No new safety concerns emerged with extended treatment.

Study details: Findings are from the 9-month open-label extension of the REGAIN trial including 1022 patients with chronic migraine who completed the preceding 3-month double-blind treatment (501, 259, and 262 patients assigned to the placebo, 120 mg galcanezumab, and 240 mg galcanezumab groups, respectively) and received a 240-mg galcanezumab loading dose, followed by 120 mg in the next month and flexible dosing thereafter.

Disclosures: This study was sponsored by Eli Lilly and Company. Some authors declared receiving speaker, consultant, or advisory board member honoraria from various sources, including Eli Lilly. Two authors reported being full-time employees and minor stockholders of Eli Lilly.

Source: Pozo-Rosich P et al. Long-term treatment with galcanezumab in patients with chronic migraine: results from the open-label extension of the REGAIN study. Curr Med Res Opin. 2022 (Apr 8). Doi:   10.1080/03007995.2022.2059975

Key clinical point: Galcanezumab is an effective and safe long-term treatment option for chronic migraine.

Major finding: At month 12, patients in the placebo, 120 mg galcanezumab, and 240 mg galcanezumab groups showed a mean change of −8.5, −9.0, and −8.0 days in monthly migraine days from the beginning of the double-blind period, respectively (all within-group P < .001). No new safety concerns emerged with extended treatment.

Study details: Findings are from the 9-month open-label extension of the REGAIN trial including 1022 patients with chronic migraine who completed the preceding 3-month double-blind treatment (501, 259, and 262 patients assigned to the placebo, 120 mg galcanezumab, and 240 mg galcanezumab groups, respectively) and received a 240-mg galcanezumab loading dose, followed by 120 mg in the next month and flexible dosing thereafter.

Disclosures: This study was sponsored by Eli Lilly and Company. Some authors declared receiving speaker, consultant, or advisory board member honoraria from various sources, including Eli Lilly. Two authors reported being full-time employees and minor stockholders of Eli Lilly.

Source: Pozo-Rosich P et al. Long-term treatment with galcanezumab in patients with chronic migraine: results from the open-label extension of the REGAIN study. Curr Med Res Opin. 2022 (Apr 8). Doi:   10.1080/03007995.2022.2059975

Key clinical point: Galcanezumab is an effective and safe long-term treatment option for chronic migraine.

Major finding: At month 12, patients in the placebo, 120 mg galcanezumab, and 240 mg galcanezumab groups showed a mean change of −8.5, −9.0, and −8.0 days in monthly migraine days from the beginning of the double-blind period, respectively (all within-group P < .001). No new safety concerns emerged with extended treatment.

Study details: Findings are from the 9-month open-label extension of the REGAIN trial including 1022 patients with chronic migraine who completed the preceding 3-month double-blind treatment (501, 259, and 262 patients assigned to the placebo, 120 mg galcanezumab, and 240 mg galcanezumab groups, respectively) and received a 240-mg galcanezumab loading dose, followed by 120 mg in the next month and flexible dosing thereafter.

Disclosures: This study was sponsored by Eli Lilly and Company. Some authors declared receiving speaker, consultant, or advisory board member honoraria from various sources, including Eli Lilly. Two authors reported being full-time employees and minor stockholders of Eli Lilly.

Source: Pozo-Rosich P et al. Long-term treatment with galcanezumab in patients with chronic migraine: results from the open-label extension of the REGAIN study. Curr Med Res Opin. 2022 (Apr 8). Doi:   10.1080/03007995.2022.2059975

A 35-year-old man comes to clinic for evaluation of new, severe headaches. He reports that these started 3 days ago. His headache is worse when he stands, and resolves when he lies down. Valsalva maneuver makes the headache much worse. The headaches are present in the occipital region. He also has noticed the onset of tinnitus. A physical exam reveals that his blood pressure is 110/70 mm Hg, his pulse is 60 beats per minute, and his temperature is 36.4° C. His standing BP is 105/60 mm Hg and standing pulse is 66 bpm. Both his neurologic exam and noncontrast head CT scan are normal.


Which of the following is the most likely diagnosis?

A) Subarachnoid hemorrhage

B) POTS (Postural orthostatic tachycardia syndrome)

C) Hypnic headache

D) Spontaneous intracranial hypotension (SIH)

E) Acoustic neuroma

The most likely cause for this patient’s headaches given his set of symptoms is spontaneous intracranial hypotension. Orthostatic headaches are common with POTS, but the absence of tachycardia with standing makes this diagnosis unlikely.

Spontaneous intracranial hypotension has symptoms that we are all familiar with in the post–lumbar puncture patient. In patients with post-LP headache, the positional nature makes it easy to diagnose. Patients who have had a lumbar puncture have a clear reason they have a cerebrospinal fluid (CSF) leak, leading to intracranial hypotension. Those with SIH do not.
 

Related research

Schievink summarized a lot of useful information in a review of patients with spontaneous intracranial hypotension.¹ The incidence is about 5/100,000, with the most common age around 40 years old. The most common symptom is orthostatic headache. The headache usually occurs within 15 minutes upon standing, and many patients have the onset of headache rapidly upon standing.

Usually the headache improves with lying down, and it is often brought on with Valsalva maneuver. Many patients report headaches that are worse in the second half of the day.

Orthostatic headache occurs in almost all patients with spontaneous intracranial hypotension, but in one series it occurred only in 77% of patients with SIH.² The patients who did not have typical headaches are more likely to have auditory symptoms such as tinnitus and muffled hearing.³

When you suspect SIH, appropriate workup is to start with brain MR imaging with contrast. Krantz and colleagues found dural enhancement was present in 83% of cases of SIH, venous distention sign in 75%, and brain sagging in 61%.⁴

About 10% of patients with SIH have normal brain imaging, so if the clinical features strongly suggest the diagnosis, moving on to spinal imaging with CT myelography or spinal MR are appropriate next steps.⁵

The causes of SIH are meningeal diverticula (usually in the thoracic or upper lumbar regions), ventral dural tears (usually from osteophytes), and cerebrospinal fluid–venous fistulas. Treatment of SIH has traditionally included a conservative approach of bed rest, oral hydration, and caffeine. The effectiveness of this is unknown, and, in one small series, 61% had headache symptoms at 6 months.⁶

Epidural blood patches are likely more rapidly effective than conservative therapy. In one study comparing the two treatments, Chung and colleagues found that 77% of the patients who received an epidural blood patch had complete headache relief at 4 weeks, compared with 40% of those who received conservative measures (P < .05).⁷
 

Clinical pearls

• Strongly consider SIH in patients with positional headache.
• Brain MR should be the first diagnostic test.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006;295:2286-96.

2. Mea E et al. Headache attributed to spontaneous intracranial hypotension. Neurol Sci. 2008;29:164-65.

3. Krantz PG et al. Spontaneous Intracranial Hypotension: 10 Myths and Misperceptions. Headache. 2018;58:948-59.

4. Krantz PG et. al. Imaging signs in spontaneous intracranial hypotension: prevalence and relationship to CSF pressure. AJNR Am J Neuroradiol. 2016;37:1374-8.

5. Krantz PG et al. Spontaneous intracranial hypotension: Pathogenesis, diagnosis, and treatment. Neuroimaging Clin N Am. 2019;29:581-94.

6. Kong D-S et. al. Clinical features and long-term results of spontaneous intracranial hypotension. Neurosurgery. 2005;57:91-6.

7. Chung SJ et al. Short- and long-term outcomes of spontaneous CSF hypovolemia. Eur Neurol. 2005;54:63-7.

A 35-year-old man comes to clinic for evaluation of new, severe headaches. He reports that these started 3 days ago. His headache is worse when he stands, and resolves when he lies down. Valsalva maneuver makes the headache much worse. The headaches are present in the occipital region. He also has noticed the onset of tinnitus. A physical exam reveals that his blood pressure is 110/70 mm Hg, his pulse is 60 beats per minute, and his temperature is 36.4° C. His standing BP is 105/60 mm Hg and standing pulse is 66 bpm. Both his neurologic exam and noncontrast head CT scan are normal.


Which of the following is the most likely diagnosis?

A) Subarachnoid hemorrhage

B) POTS (Postural orthostatic tachycardia syndrome)

C) Hypnic headache

D) Spontaneous intracranial hypotension (SIH)

E) Acoustic neuroma

The most likely cause for this patient’s headaches given his set of symptoms is spontaneous intracranial hypotension. Orthostatic headaches are common with POTS, but the absence of tachycardia with standing makes this diagnosis unlikely.

Spontaneous intracranial hypotension has symptoms that we are all familiar with in the post–lumbar puncture patient. In patients with post-LP headache, the positional nature makes it easy to diagnose. Patients who have had a lumbar puncture have a clear reason they have a cerebrospinal fluid (CSF) leak, leading to intracranial hypotension. Those with SIH do not.
 

Related research

Schievink summarized a lot of useful information in a review of patients with spontaneous intracranial hypotension.¹ The incidence is about 5/100,000, with the most common age around 40 years old. The most common symptom is orthostatic headache. The headache usually occurs within 15 minutes upon standing, and many patients have the onset of headache rapidly upon standing.

Usually the headache improves with lying down, and it is often brought on with Valsalva maneuver. Many patients report headaches that are worse in the second half of the day.

Orthostatic headache occurs in almost all patients with spontaneous intracranial hypotension, but in one series it occurred only in 77% of patients with SIH.² The patients who did not have typical headaches are more likely to have auditory symptoms such as tinnitus and muffled hearing.³

When you suspect SIH, appropriate workup is to start with brain MR imaging with contrast. Krantz and colleagues found dural enhancement was present in 83% of cases of SIH, venous distention sign in 75%, and brain sagging in 61%.⁴

About 10% of patients with SIH have normal brain imaging, so if the clinical features strongly suggest the diagnosis, moving on to spinal imaging with CT myelography or spinal MR are appropriate next steps.⁵

The causes of SIH are meningeal diverticula (usually in the thoracic or upper lumbar regions), ventral dural tears (usually from osteophytes), and cerebrospinal fluid–venous fistulas. Treatment of SIH has traditionally included a conservative approach of bed rest, oral hydration, and caffeine. The effectiveness of this is unknown, and, in one small series, 61% had headache symptoms at 6 months.⁶

Epidural blood patches are likely more rapidly effective than conservative therapy. In one study comparing the two treatments, Chung and colleagues found that 77% of the patients who received an epidural blood patch had complete headache relief at 4 weeks, compared with 40% of those who received conservative measures (P < .05).⁷
 

Clinical pearls

• Strongly consider SIH in patients with positional headache.
• Brain MR should be the first diagnostic test.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006;295:2286-96.

2. Mea E et al. Headache attributed to spontaneous intracranial hypotension. Neurol Sci. 2008;29:164-65.

3. Krantz PG et al. Spontaneous Intracranial Hypotension: 10 Myths and Misperceptions. Headache. 2018;58:948-59.

4. Krantz PG et. al. Imaging signs in spontaneous intracranial hypotension: prevalence and relationship to CSF pressure. AJNR Am J Neuroradiol. 2016;37:1374-8.

5. Krantz PG et al. Spontaneous intracranial hypotension: Pathogenesis, diagnosis, and treatment. Neuroimaging Clin N Am. 2019;29:581-94.

6. Kong D-S et. al. Clinical features and long-term results of spontaneous intracranial hypotension. Neurosurgery. 2005;57:91-6.

7. Chung SJ et al. Short- and long-term outcomes of spontaneous CSF hypovolemia. Eur Neurol. 2005;54:63-7.

A 35-year-old man comes to clinic for evaluation of new, severe headaches. He reports that these started 3 days ago. His headache is worse when he stands, and resolves when he lies down. Valsalva maneuver makes the headache much worse. The headaches are present in the occipital region. He also has noticed the onset of tinnitus. A physical exam reveals that his blood pressure is 110/70 mm Hg, his pulse is 60 beats per minute, and his temperature is 36.4° C. His standing BP is 105/60 mm Hg and standing pulse is 66 bpm. Both his neurologic exam and noncontrast head CT scan are normal.


Which of the following is the most likely diagnosis?

A) Subarachnoid hemorrhage

B) POTS (Postural orthostatic tachycardia syndrome)

C) Hypnic headache

D) Spontaneous intracranial hypotension (SIH)

E) Acoustic neuroma

The most likely cause for this patient’s headaches given his set of symptoms is spontaneous intracranial hypotension. Orthostatic headaches are common with POTS, but the absence of tachycardia with standing makes this diagnosis unlikely.

Spontaneous intracranial hypotension has symptoms that we are all familiar with in the post–lumbar puncture patient. In patients with post-LP headache, the positional nature makes it easy to diagnose. Patients who have had a lumbar puncture have a clear reason they have a cerebrospinal fluid (CSF) leak, leading to intracranial hypotension. Those with SIH do not.
 

Related research

Schievink summarized a lot of useful information in a review of patients with spontaneous intracranial hypotension.¹ The incidence is about 5/100,000, with the most common age around 40 years old. The most common symptom is orthostatic headache. The headache usually occurs within 15 minutes upon standing, and many patients have the onset of headache rapidly upon standing.

Usually the headache improves with lying down, and it is often brought on with Valsalva maneuver. Many patients report headaches that are worse in the second half of the day.

Orthostatic headache occurs in almost all patients with spontaneous intracranial hypotension, but in one series it occurred only in 77% of patients with SIH.² The patients who did not have typical headaches are more likely to have auditory symptoms such as tinnitus and muffled hearing.³

When you suspect SIH, appropriate workup is to start with brain MR imaging with contrast. Krantz and colleagues found dural enhancement was present in 83% of cases of SIH, venous distention sign in 75%, and brain sagging in 61%.⁴

About 10% of patients with SIH have normal brain imaging, so if the clinical features strongly suggest the diagnosis, moving on to spinal imaging with CT myelography or spinal MR are appropriate next steps.⁵

The causes of SIH are meningeal diverticula (usually in the thoracic or upper lumbar regions), ventral dural tears (usually from osteophytes), and cerebrospinal fluid–venous fistulas. Treatment of SIH has traditionally included a conservative approach of bed rest, oral hydration, and caffeine. The effectiveness of this is unknown, and, in one small series, 61% had headache symptoms at 6 months.⁶

Epidural blood patches are likely more rapidly effective than conservative therapy. In one study comparing the two treatments, Chung and colleagues found that 77% of the patients who received an epidural blood patch had complete headache relief at 4 weeks, compared with 40% of those who received conservative measures (P < .05).⁷
 

Clinical pearls

• Strongly consider SIH in patients with positional headache.
• Brain MR should be the first diagnostic test.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as 3rd-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006;295:2286-96.

2. Mea E et al. Headache attributed to spontaneous intracranial hypotension. Neurol Sci. 2008;29:164-65.

3. Krantz PG et al. Spontaneous Intracranial Hypotension: 10 Myths and Misperceptions. Headache. 2018;58:948-59.

4. Krantz PG et. al. Imaging signs in spontaneous intracranial hypotension: prevalence and relationship to CSF pressure. AJNR Am J Neuroradiol. 2016;37:1374-8.

5. Krantz PG et al. Spontaneous intracranial hypotension: Pathogenesis, diagnosis, and treatment. Neuroimaging Clin N Am. 2019;29:581-94.

6. Kong D-S et. al. Clinical features and long-term results of spontaneous intracranial hypotension. Neurosurgery. 2005;57:91-6.

7. Chung SJ et al. Short- and long-term outcomes of spontaneous CSF hypovolemia. Eur Neurol. 2005;54:63-7.

Topiramate, introduced as an antiepileptic drug (AED), is currently most widely used for prevention of migraine headaches.

Because reproductive-aged women represent a population in which migraines are prevalent, clinicians need guidance to help women taking topiramate make sound contraceptive choices.

Several issues are relevant here. First, women who have migraines with aura should avoid estrogen-containing contraceptive pills, patches, and rings. Instead, progestin-only methods, including the contraceptive implant, may be recommended to patients with migraines.

Second, because topiramate, as with a number of other AEDs, is a teratogen, women using this medication need highly effective contraception. This consideration may also lead clinicians to recommend use of the implant in women with migraines.

Finally, topiramate, along with other AEDs (phenytoin, carbamazepine, barbiturates, primidone, and oxcarbazepine) induces hepatic enzymes, which results in reduced serum contraceptive steroid levels.

Because there is uncertainty regarding the degree to which the use of topiramate reduces serum levels of etonogestrel (the progestin released by the implant), investigators performed a prospective study to assess the pharmacokinetic impact of topiramate in women with the implant.

Ongoing users of contraceptive implants who agreed to use additional nonhormonal contraception were recruited to a 6-week study, during which they took topiramate and periodically had blood drawn.

Overall, use of topiramate was found to lower serum etonogestrel levels from baseline on a dose-related basis. At study completion, almost one-third of study participants were found to have serum progestin levels lower than the threshold associated with predictable ovulation suppression.

The results of this carefully conducted study support guidance from the Centers for Disease Control and Prevention that women seeking contraception and using topiramate or other enzyme-inducing AEDs should be encouraged to use intrauterine devices or injectable contraception. The contraceptive efficacy of these latter methods is not diminished by concomitant use of enzyme inducers.

I am Andrew Kaunitz. Please take care of yourself and each other.

Any views expressed above are the author’s own and do not necessarily reflect the views of WebMD or Medscape.

Andrew M. Kaunitz is a professor and Associate Chairman, department of obstetrics and gynecology, University of Florida, Jacksonville.

A version of this article first appeared on Medscape.com.

Topiramate, introduced as an antiepileptic drug (AED), is currently most widely used for prevention of migraine headaches.

Because reproductive-aged women represent a population in which migraines are prevalent, clinicians need guidance to help women taking topiramate make sound contraceptive choices.

Several issues are relevant here. First, women who have migraines with aura should avoid estrogen-containing contraceptive pills, patches, and rings. Instead, progestin-only methods, including the contraceptive implant, may be recommended to patients with migraines.

Second, because topiramate, as with a number of other AEDs, is a teratogen, women using this medication need highly effective contraception. This consideration may also lead clinicians to recommend use of the implant in women with migraines.

Finally, topiramate, along with other AEDs (phenytoin, carbamazepine, barbiturates, primidone, and oxcarbazepine) induces hepatic enzymes, which results in reduced serum contraceptive steroid levels.

Because there is uncertainty regarding the degree to which the use of topiramate reduces serum levels of etonogestrel (the progestin released by the implant), investigators performed a prospective study to assess the pharmacokinetic impact of topiramate in women with the implant.

Ongoing users of contraceptive implants who agreed to use additional nonhormonal contraception were recruited to a 6-week study, during which they took topiramate and periodically had blood drawn.

Overall, use of topiramate was found to lower serum etonogestrel levels from baseline on a dose-related basis. At study completion, almost one-third of study participants were found to have serum progestin levels lower than the threshold associated with predictable ovulation suppression.

The results of this carefully conducted study support guidance from the Centers for Disease Control and Prevention that women seeking contraception and using topiramate or other enzyme-inducing AEDs should be encouraged to use intrauterine devices or injectable contraception. The contraceptive efficacy of these latter methods is not diminished by concomitant use of enzyme inducers.

I am Andrew Kaunitz. Please take care of yourself and each other.

Any views expressed above are the author’s own and do not necessarily reflect the views of WebMD or Medscape.

Andrew M. Kaunitz is a professor and Associate Chairman, department of obstetrics and gynecology, University of Florida, Jacksonville.

A version of this article first appeared on Medscape.com.

Topiramate, introduced as an antiepileptic drug (AED), is currently most widely used for prevention of migraine headaches.

Because reproductive-aged women represent a population in which migraines are prevalent, clinicians need guidance to help women taking topiramate make sound contraceptive choices.

Several issues are relevant here. First, women who have migraines with aura should avoid estrogen-containing contraceptive pills, patches, and rings. Instead, progestin-only methods, including the contraceptive implant, may be recommended to patients with migraines.

Second, because topiramate, as with a number of other AEDs, is a teratogen, women using this medication need highly effective contraception. This consideration may also lead clinicians to recommend use of the implant in women with migraines.

Finally, topiramate, along with other AEDs (phenytoin, carbamazepine, barbiturates, primidone, and oxcarbazepine) induces hepatic enzymes, which results in reduced serum contraceptive steroid levels.

Because there is uncertainty regarding the degree to which the use of topiramate reduces serum levels of etonogestrel (the progestin released by the implant), investigators performed a prospective study to assess the pharmacokinetic impact of topiramate in women with the implant.

Ongoing users of contraceptive implants who agreed to use additional nonhormonal contraception were recruited to a 6-week study, during which they took topiramate and periodically had blood drawn.

Overall, use of topiramate was found to lower serum etonogestrel levels from baseline on a dose-related basis. At study completion, almost one-third of study participants were found to have serum progestin levels lower than the threshold associated with predictable ovulation suppression.

The results of this carefully conducted study support guidance from the Centers for Disease Control and Prevention that women seeking contraception and using topiramate or other enzyme-inducing AEDs should be encouraged to use intrauterine devices or injectable contraception. The contraceptive efficacy of these latter methods is not diminished by concomitant use of enzyme inducers.

I am Andrew Kaunitz. Please take care of yourself and each other.

Any views expressed above are the author’s own and do not necessarily reflect the views of WebMD or Medscape.

Andrew M. Kaunitz is a professor and Associate Chairman, department of obstetrics and gynecology, University of Florida, Jacksonville.

A version of this article first appeared on Medscape.com.

Approximately one in five patients who presented with headache during the acute phase of COVID-19 developed chronic daily headache, according to a study published in Cephalalgia. The greater the headache’s intensity during the acute phase, the greater the likelihood that it would persist.

The research, carried out by members of the Headache Study Group of the Spanish Society of Neurology, evaluated the evolution of headache in more than 900 Spanish patients. Because they found that headache intensity during the acute phase was associated with a more prolonged duration of headache, the team stressed the importance of promptly evaluating patients who have had COVID-19 and who then experience persistent headache.
 

Long-term evolution unknown

Headache is a common symptom of COVID-19, but its long-term evolution remains unknown. The objective of this study was to evaluate the long-term duration of headache in patients who presented with this symptom during the acute phase of the disease.

Recruitment for this multicenter study took place in March and April 2020. The 905 patients who were enrolled came from six level 3 hospitals in Spain. All completed 9 months of neurologic follow-up.

Their median age was 51 years, 66.5% were women, and more than half (52.7%) had a history of primary headache. About half of the patients required hospitalization (50.5%); the rest were treated as outpatients. The most common headache phenotype was holocranial (67.8%) of severe intensity (50.6%).
 

Persistent headache common

In the 96.6% cases for which data were available, the median duration of headache was 14 days. The headache persisted at 1 month in 31.1% of patients, at 2 months in 21.5%, at 3 months in 19%, at 6 months in 16.8%, and at 9 months in 16.0%.

“The median duration of COVID-19 headache is around 2 weeks,” David García Azorín, MD, PhD, a member of the Spanish Society of Neurology and one of the coauthors of the study, said in an interview. “However, almost 20% of patients experience it for longer than that. When still present at 2 months, the headache is more likely to follow a chronic daily pattern.” Dr. García Azorín is a neurologist and clinical researcher at the headache unit of the Hospital Clínico Universitario in Valladolid, Spain.

“So, if the headache isn’t letting up, it’s important to make the most of that window of opportunity and provide treatment in that period of 6-12 weeks,” he continued. “To do this, the best option is to carry out preventive treatment so that the patient will have a better chance of recovering.”

Study participants whose headache persisted at 9 months were older and were mostly women. They were less likely to have had pneumonia or to have experienced stabbing pain, photophobia, or phonophobia. They reported that the headache got worse when they engaged in physical activity but less frequently manifested as a throbbing headache.
 

Secondary tension headaches

On the other hand, Jaime Rodríguez Vico, MD, head of the headache unit at the Jiménez Díaz Foundation Hospital in Madrid, said in an interview that, according to his case studies, the most striking characteristics of post–COVID-19 headaches “in general are secondary, with similarities to tension headaches that patients are able to differentiate from other clinical types of headache. In patients with migraine, very often we see that we’re dealing with a trigger. In other words, more migraines – and more intense ones at that – are brought about.”

He added: “Generally, post–COVID-19 headache usually lasts 1-2 weeks, but we have cases of it lasting several months and even over a year with persistent daily headache. These more persistent cases are probably connected to another type of pathology that makes them more susceptible to becoming chronic, something that occurs in another type of primary headache known as new daily persistent headache.”
 

Primary headache exacerbation

Dr. García Azorín pointed out that it’s not uncommon that among people who already have primary headache, their condition worsens after they become infected with SARS-CoV-2. However, many people differentiate the headache associated with the infection from their usual headache because after becoming infected, their headache is predominantly frontal, oppressive, and chronic.

“Having a prior history of headache is one of the factors that can increase the likelihood that a headache experienced while suffering from COVID-19 will become chronic,” he noted.

This study also found that, more often than not, patients with persistent headache at 9 months had migraine-like pain.

As for headaches in these patients beyond 9 months, “based on our research, the evolution is quite variable,” said Dr. Rodríguez Vico. “Our unit’s numbers are skewed due to the high number of migraine cases that we follow, and therefore our high volume of migraine patients who’ve gotten worse. The same thing happens with COVID-19 vaccines. Migraine is a polygenic disorder with multiple variants and a pathophysiology that we are just beginning to describe. This is why one patient is completely different from another. It’s a real challenge.”

Infections are a common cause of acute and chronic headache. The persistence of a headache after an infection may be caused by the infection becoming chronic, as happens in some types of chronic meningitis, such as tuberculous meningitis. It may also be caused by the persistence of a certain response and activation of the immune system or to the uncovering or worsening of a primary headache coincident with the infection, added Dr. García Azorín.

“Likewise, there are other people who have a biological predisposition to headache as a multifactorial disorder and polygenic disorder, such that a particular stimulus – from trauma or an infection to alcohol consumption – can cause them to develop a headache very similar to a migraine,” he said.
 

Providing prognosis and treatment

Certain factors can give an idea of how long the headache might last. The study’s univariate analysis showed that age, female sex, headache intensity, pressure-like quality, the presence of photophobia/phonophobia, and worsening with physical activity were associated with headache of longer duration. But in the multivariate analysis, only headache intensity during the acute phase remained statistically significant (hazard ratio, 0.655; 95% confidence interval, 0.582-0.737; P < .001).

When asked whether they planned to continue the study, Dr. García Azorín commented, “The main questions that have arisen from this study have been, above all: ‘Why does this headache happen?’ and ‘How can it be treated or avoided?’ To answer them, we’re looking into pain: which factors could predispose a person to it and which changes may be associated with its presence.”

In addition, different treatments that may improve patient outcomes are being evaluated, because to date, treatment has been empirical and based on the predominant pain phenotype.

In any case, most doctors currently treat post–COVID-19 headache on the basis of how similar the symptoms are to those of other primary headaches. “Given the impact that headache has on patients’ quality of life, there’s a pressing need for controlled studies on possible treatments and their effectiveness,” noted Patricia Pozo Rosich, MD, PhD, one of the coauthors of the study.

“We at the Spanish Society of Neurology truly believe that if these patients were to have this symptom correctly addressed from the start, they could avoid many of the problems that arise in the situation becoming chronic,” she concluded.

Dr. García Azorín and Dr. Rodríguez Vico disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Approximately one in five patients who presented with headache during the acute phase of COVID-19 developed chronic daily headache, according to a study published in Cephalalgia. The greater the headache’s intensity during the acute phase, the greater the likelihood that it would persist.

The research, carried out by members of the Headache Study Group of the Spanish Society of Neurology, evaluated the evolution of headache in more than 900 Spanish patients. Because they found that headache intensity during the acute phase was associated with a more prolonged duration of headache, the team stressed the importance of promptly evaluating patients who have had COVID-19 and who then experience persistent headache.
 

Long-term evolution unknown

Headache is a common symptom of COVID-19, but its long-term evolution remains unknown. The objective of this study was to evaluate the long-term duration of headache in patients who presented with this symptom during the acute phase of the disease.

Recruitment for this multicenter study took place in March and April 2020. The 905 patients who were enrolled came from six level 3 hospitals in Spain. All completed 9 months of neurologic follow-up.

Their median age was 51 years, 66.5% were women, and more than half (52.7%) had a history of primary headache. About half of the patients required hospitalization (50.5%); the rest were treated as outpatients. The most common headache phenotype was holocranial (67.8%) of severe intensity (50.6%).
 

Persistent headache common

In the 96.6% cases for which data were available, the median duration of headache was 14 days. The headache persisted at 1 month in 31.1% of patients, at 2 months in 21.5%, at 3 months in 19%, at 6 months in 16.8%, and at 9 months in 16.0%.

“The median duration of COVID-19 headache is around 2 weeks,” David García Azorín, MD, PhD, a member of the Spanish Society of Neurology and one of the coauthors of the study, said in an interview. “However, almost 20% of patients experience it for longer than that. When still present at 2 months, the headache is more likely to follow a chronic daily pattern.” Dr. García Azorín is a neurologist and clinical researcher at the headache unit of the Hospital Clínico Universitario in Valladolid, Spain.

“So, if the headache isn’t letting up, it’s important to make the most of that window of opportunity and provide treatment in that period of 6-12 weeks,” he continued. “To do this, the best option is to carry out preventive treatment so that the patient will have a better chance of recovering.”

Study participants whose headache persisted at 9 months were older and were mostly women. They were less likely to have had pneumonia or to have experienced stabbing pain, photophobia, or phonophobia. They reported that the headache got worse when they engaged in physical activity but less frequently manifested as a throbbing headache.
 

Secondary tension headaches

On the other hand, Jaime Rodríguez Vico, MD, head of the headache unit at the Jiménez Díaz Foundation Hospital in Madrid, said in an interview that, according to his case studies, the most striking characteristics of post–COVID-19 headaches “in general are secondary, with similarities to tension headaches that patients are able to differentiate from other clinical types of headache. In patients with migraine, very often we see that we’re dealing with a trigger. In other words, more migraines – and more intense ones at that – are brought about.”

He added: “Generally, post–COVID-19 headache usually lasts 1-2 weeks, but we have cases of it lasting several months and even over a year with persistent daily headache. These more persistent cases are probably connected to another type of pathology that makes them more susceptible to becoming chronic, something that occurs in another type of primary headache known as new daily persistent headache.”
 

Primary headache exacerbation

Dr. García Azorín pointed out that it’s not uncommon that among people who already have primary headache, their condition worsens after they become infected with SARS-CoV-2. However, many people differentiate the headache associated with the infection from their usual headache because after becoming infected, their headache is predominantly frontal, oppressive, and chronic.

“Having a prior history of headache is one of the factors that can increase the likelihood that a headache experienced while suffering from COVID-19 will become chronic,” he noted.

This study also found that, more often than not, patients with persistent headache at 9 months had migraine-like pain.

As for headaches in these patients beyond 9 months, “based on our research, the evolution is quite variable,” said Dr. Rodríguez Vico. “Our unit’s numbers are skewed due to the high number of migraine cases that we follow, and therefore our high volume of migraine patients who’ve gotten worse. The same thing happens with COVID-19 vaccines. Migraine is a polygenic disorder with multiple variants and a pathophysiology that we are just beginning to describe. This is why one patient is completely different from another. It’s a real challenge.”

Infections are a common cause of acute and chronic headache. The persistence of a headache after an infection may be caused by the infection becoming chronic, as happens in some types of chronic meningitis, such as tuberculous meningitis. It may also be caused by the persistence of a certain response and activation of the immune system or to the uncovering or worsening of a primary headache coincident with the infection, added Dr. García Azorín.

“Likewise, there are other people who have a biological predisposition to headache as a multifactorial disorder and polygenic disorder, such that a particular stimulus – from trauma or an infection to alcohol consumption – can cause them to develop a headache very similar to a migraine,” he said.
 

Providing prognosis and treatment

Certain factors can give an idea of how long the headache might last. The study’s univariate analysis showed that age, female sex, headache intensity, pressure-like quality, the presence of photophobia/phonophobia, and worsening with physical activity were associated with headache of longer duration. But in the multivariate analysis, only headache intensity during the acute phase remained statistically significant (hazard ratio, 0.655; 95% confidence interval, 0.582-0.737; P < .001).

When asked whether they planned to continue the study, Dr. García Azorín commented, “The main questions that have arisen from this study have been, above all: ‘Why does this headache happen?’ and ‘How can it be treated or avoided?’ To answer them, we’re looking into pain: which factors could predispose a person to it and which changes may be associated with its presence.”

In addition, different treatments that may improve patient outcomes are being evaluated, because to date, treatment has been empirical and based on the predominant pain phenotype.

In any case, most doctors currently treat post–COVID-19 headache on the basis of how similar the symptoms are to those of other primary headaches. “Given the impact that headache has on patients’ quality of life, there’s a pressing need for controlled studies on possible treatments and their effectiveness,” noted Patricia Pozo Rosich, MD, PhD, one of the coauthors of the study.

“We at the Spanish Society of Neurology truly believe that if these patients were to have this symptom correctly addressed from the start, they could avoid many of the problems that arise in the situation becoming chronic,” she concluded.

Dr. García Azorín and Dr. Rodríguez Vico disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Approximately one in five patients who presented with headache during the acute phase of COVID-19 developed chronic daily headache, according to a study published in Cephalalgia. The greater the headache’s intensity during the acute phase, the greater the likelihood that it would persist.

The research, carried out by members of the Headache Study Group of the Spanish Society of Neurology, evaluated the evolution of headache in more than 900 Spanish patients. Because they found that headache intensity during the acute phase was associated with a more prolonged duration of headache, the team stressed the importance of promptly evaluating patients who have had COVID-19 and who then experience persistent headache.
 

Long-term evolution unknown

Headache is a common symptom of COVID-19, but its long-term evolution remains unknown. The objective of this study was to evaluate the long-term duration of headache in patients who presented with this symptom during the acute phase of the disease.

Recruitment for this multicenter study took place in March and April 2020. The 905 patients who were enrolled came from six level 3 hospitals in Spain. All completed 9 months of neurologic follow-up.

Their median age was 51 years, 66.5% were women, and more than half (52.7%) had a history of primary headache. About half of the patients required hospitalization (50.5%); the rest were treated as outpatients. The most common headache phenotype was holocranial (67.8%) of severe intensity (50.6%).
 

Persistent headache common

In the 96.6% cases for which data were available, the median duration of headache was 14 days. The headache persisted at 1 month in 31.1% of patients, at 2 months in 21.5%, at 3 months in 19%, at 6 months in 16.8%, and at 9 months in 16.0%.

“The median duration of COVID-19 headache is around 2 weeks,” David García Azorín, MD, PhD, a member of the Spanish Society of Neurology and one of the coauthors of the study, said in an interview. “However, almost 20% of patients experience it for longer than that. When still present at 2 months, the headache is more likely to follow a chronic daily pattern.” Dr. García Azorín is a neurologist and clinical researcher at the headache unit of the Hospital Clínico Universitario in Valladolid, Spain.

“So, if the headache isn’t letting up, it’s important to make the most of that window of opportunity and provide treatment in that period of 6-12 weeks,” he continued. “To do this, the best option is to carry out preventive treatment so that the patient will have a better chance of recovering.”

Study participants whose headache persisted at 9 months were older and were mostly women. They were less likely to have had pneumonia or to have experienced stabbing pain, photophobia, or phonophobia. They reported that the headache got worse when they engaged in physical activity but less frequently manifested as a throbbing headache.
 

Secondary tension headaches

On the other hand, Jaime Rodríguez Vico, MD, head of the headache unit at the Jiménez Díaz Foundation Hospital in Madrid, said in an interview that, according to his case studies, the most striking characteristics of post–COVID-19 headaches “in general are secondary, with similarities to tension headaches that patients are able to differentiate from other clinical types of headache. In patients with migraine, very often we see that we’re dealing with a trigger. In other words, more migraines – and more intense ones at that – are brought about.”

He added: “Generally, post–COVID-19 headache usually lasts 1-2 weeks, but we have cases of it lasting several months and even over a year with persistent daily headache. These more persistent cases are probably connected to another type of pathology that makes them more susceptible to becoming chronic, something that occurs in another type of primary headache known as new daily persistent headache.”
 

Primary headache exacerbation

Dr. García Azorín pointed out that it’s not uncommon that among people who already have primary headache, their condition worsens after they become infected with SARS-CoV-2. However, many people differentiate the headache associated with the infection from their usual headache because after becoming infected, their headache is predominantly frontal, oppressive, and chronic.

“Having a prior history of headache is one of the factors that can increase the likelihood that a headache experienced while suffering from COVID-19 will become chronic,” he noted.

This study also found that, more often than not, patients with persistent headache at 9 months had migraine-like pain.

As for headaches in these patients beyond 9 months, “based on our research, the evolution is quite variable,” said Dr. Rodríguez Vico. “Our unit’s numbers are skewed due to the high number of migraine cases that we follow, and therefore our high volume of migraine patients who’ve gotten worse. The same thing happens with COVID-19 vaccines. Migraine is a polygenic disorder with multiple variants and a pathophysiology that we are just beginning to describe. This is why one patient is completely different from another. It’s a real challenge.”

Infections are a common cause of acute and chronic headache. The persistence of a headache after an infection may be caused by the infection becoming chronic, as happens in some types of chronic meningitis, such as tuberculous meningitis. It may also be caused by the persistence of a certain response and activation of the immune system or to the uncovering or worsening of a primary headache coincident with the infection, added Dr. García Azorín.

“Likewise, there are other people who have a biological predisposition to headache as a multifactorial disorder and polygenic disorder, such that a particular stimulus – from trauma or an infection to alcohol consumption – can cause them to develop a headache very similar to a migraine,” he said.
 

Providing prognosis and treatment

Certain factors can give an idea of how long the headache might last. The study’s univariate analysis showed that age, female sex, headache intensity, pressure-like quality, the presence of photophobia/phonophobia, and worsening with physical activity were associated with headache of longer duration. But in the multivariate analysis, only headache intensity during the acute phase remained statistically significant (hazard ratio, 0.655; 95% confidence interval, 0.582-0.737; P < .001).

When asked whether they planned to continue the study, Dr. García Azorín commented, “The main questions that have arisen from this study have been, above all: ‘Why does this headache happen?’ and ‘How can it be treated or avoided?’ To answer them, we’re looking into pain: which factors could predispose a person to it and which changes may be associated with its presence.”

In addition, different treatments that may improve patient outcomes are being evaluated, because to date, treatment has been empirical and based on the predominant pain phenotype.

In any case, most doctors currently treat post–COVID-19 headache on the basis of how similar the symptoms are to those of other primary headaches. “Given the impact that headache has on patients’ quality of life, there’s a pressing need for controlled studies on possible treatments and their effectiveness,” noted Patricia Pozo Rosich, MD, PhD, one of the coauthors of the study.

“We at the Spanish Society of Neurology truly believe that if these patients were to have this symptom correctly addressed from the start, they could avoid many of the problems that arise in the situation becoming chronic,” she concluded.

Dr. García Azorín and Dr. Rodríguez Vico disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.