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The Centers for Disease Control and Prevention has identified it as a sentinel symptom of COVID-19 disease. “A lot of the recommendations surrounding post-COVID headache is that if you identify a patient who has headaches associated with fever, and myalgia, and other systemic symptoms, the specificity of a COVID-19 diagnosis goes up. So [COVID-19] is a really important feature to look out for in patients with headache,” Deena Kuruvilla, MD, said during a presentation on post–COVID-19 headache at the 2021 Scottsdale Headache Symposium.
Estimates of the prevalence of headache in COVID-19 range widely, from 6.5% to 71%, but Dr. Kuruvilla has plenty of personal experience with it. “During my stint on the inpatient neurology service during the peak of COVID, I saw patients with headache being one of the most frequent complaints, [along with] dizziness, stroke, and seizure among many other neurological manifestations,” said Dr. Kuruvilla, director of the Westport (Conn.) Headache Institute.
One meta-analysis showed that 47% of patients with COVID-19 complain of headache within 30 days of diagnosis, and this drops to around 10% at 60-90 days, and around 8% at 180 days.
A survey of 3,458 patients, published in the Journal of Headache Pain, found that migraine is the most common type of post–COVID-19 headache phenotype, and patients reporting anosmia-ageusia were more likely to have post–COVID-19 headache (odds ratio [OR], 5.39; 95% confidence interval, 1.66-17.45).
A case-control study of post–COVID-19 headache patients with and without a history of migraine found that those with a history of migraine were more likely to have post–COVID-19 symptoms (OR, 1.70; P < .001) and fatigue (OR, 2.89; P = .008). “Interestingly, they found no difference in headache as post-COVID symptoms in people who had a history of migraine compared with people without a history of migraine,” said Dr. Kuruvilla.
Headache and COVID-19: What is the connection?
Several mechanisms have been proposed for direct invasion of the central nervous system, either via infection through the angiotensin-converting enzyme 2 (ACE-2) receptor, which is expressed in brain regions including the motor cortex, the posterior cingulate cortex, and the olfactory bulb, among other locations. Another potential mechanism is direct entry through the olfactory nerve and the associated olfactory epithelium. There are various potential mechanisms for spread among the peripheral nervous system, and the blood-brain barrier can be compromised by infection of vascular endothelial cells. According to the literature, neuronal damage seems to occur directly from viral damage rather than from the immune response, said Dr. Kuruvilla.
The virus may also gain entry to the CNS indirectly, as a result of hypoxia and metabolic disturbances, as well as dehydration and systematic inflammation. The cytokine storm associated with COVID-19 infection can activate C-reactive protein and calcitonin gene-related peptide (CGRP), which plays a key role in migraine pathology. The CGRP receptor antagonist vazegepant is being studied in a phase 2 clinical trial for the treatment of COVID-19–related lung inflammation.
Testing and treatment
“If I see patients with new headache, worsening headache from their baseline, or headache with systemic symptoms, I often consider screening them for COVID. If that screening is positive, I proceed with PCR testing. I also consider an MRI of the brain with and without gadolinium just to rule out any secondary causes for headache,” said Dr. Kuruvilla, noting that she has diagnosed patients with venous sinus thrombosis, ischemic stroke, and meningitis following COVID-19.
The existing literature suggests that lumbar puncture in patients with SARS-CoV-2 typically returns normal results, but Dr. Kuruvilla proceeds with it anyway with viral, bacterial, fungal, and autoimmune studies to rule out potential secondary causes for headache.
There are few studies on how to treat post–COVID-19 headache, and the general recommendation is that headache phenotype should drive treatment decisions.
In a case series, three patients with persistent headache following mild COVID-19 infection were treated with onabotulinumtoxinA and amitriptyline. They had daily headaches, along with post–COVID-19 symptoms including fatigue and insomnia. After treatment, each patient converted to episodic headaches.
One retrospective study of 37 patients found that a 5-day course of indomethacin 50 mg twice per day and pantoprazole 40 mg once per day was associated with a 50% or greater improvement in headache on the third day in 36 of the 37 patients. Five patients were free of pain by day 5.
A common problem
Neurologists have been involved in the treatment of COVID-19 since the beginning, and post–COVID-19 headache has added another layer. “It’s been a remarkably common clinical problem. And the fact that it’s actually reached the level of headache specialist actually shows that in some cases, it’s really quite a significant problem, in both its severity and persistence. So I think it’s a very, very significant issue,” said Andrew Charles, MD, professor of neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program.
Dr. Kuruvilla also discussed the question of whether neurological damage is due to direct damage from the virus, or indirect damage from an immune response. This was debated during the Q&A session following Dr. Kuruvilla’s talk, and it was pointed out that headache is a frequent side effect of the Pfizer and Moderna vaccines.
“It’s a huge open question about how much is direct invasion or damage or not even damage, but just change in function with the viral infection, as opposed to inflammation. The fact that very often the response to the vaccine is similar to what you see with COVID suggests that at least some component of it is inflammation. I wouldn’t commit to one mechanism or the other, but I’d say that it’s possible that it’s really both,” said Dr. Charles.
Dr. Kuruvilla has consulted for Cefaly, Neurolief, Theranica, Now What Media, and KX advisors. She has been on the speakers bureau for Abbvie/Allergan, Amgen/Novartis, and Lilly. She has been on advisory boards for Abbvie/Allergan, Lilly, Theranica, and Amgen/Novartis. Dr. Charles has no relevant financial disclosures.
The Centers for Disease Control and Prevention has identified it as a sentinel symptom of COVID-19 disease. “A lot of the recommendations surrounding post-COVID headache is that if you identify a patient who has headaches associated with fever, and myalgia, and other systemic symptoms, the specificity of a COVID-19 diagnosis goes up. So [COVID-19] is a really important feature to look out for in patients with headache,” Deena Kuruvilla, MD, said during a presentation on post–COVID-19 headache at the 2021 Scottsdale Headache Symposium.
Estimates of the prevalence of headache in COVID-19 range widely, from 6.5% to 71%, but Dr. Kuruvilla has plenty of personal experience with it. “During my stint on the inpatient neurology service during the peak of COVID, I saw patients with headache being one of the most frequent complaints, [along with] dizziness, stroke, and seizure among many other neurological manifestations,” said Dr. Kuruvilla, director of the Westport (Conn.) Headache Institute.
One meta-analysis showed that 47% of patients with COVID-19 complain of headache within 30 days of diagnosis, and this drops to around 10% at 60-90 days, and around 8% at 180 days.
A survey of 3,458 patients, published in the Journal of Headache Pain, found that migraine is the most common type of post–COVID-19 headache phenotype, and patients reporting anosmia-ageusia were more likely to have post–COVID-19 headache (odds ratio [OR], 5.39; 95% confidence interval, 1.66-17.45).
A case-control study of post–COVID-19 headache patients with and without a history of migraine found that those with a history of migraine were more likely to have post–COVID-19 symptoms (OR, 1.70; P < .001) and fatigue (OR, 2.89; P = .008). “Interestingly, they found no difference in headache as post-COVID symptoms in people who had a history of migraine compared with people without a history of migraine,” said Dr. Kuruvilla.
Headache and COVID-19: What is the connection?
Several mechanisms have been proposed for direct invasion of the central nervous system, either via infection through the angiotensin-converting enzyme 2 (ACE-2) receptor, which is expressed in brain regions including the motor cortex, the posterior cingulate cortex, and the olfactory bulb, among other locations. Another potential mechanism is direct entry through the olfactory nerve and the associated olfactory epithelium. There are various potential mechanisms for spread among the peripheral nervous system, and the blood-brain barrier can be compromised by infection of vascular endothelial cells. According to the literature, neuronal damage seems to occur directly from viral damage rather than from the immune response, said Dr. Kuruvilla.
The virus may also gain entry to the CNS indirectly, as a result of hypoxia and metabolic disturbances, as well as dehydration and systematic inflammation. The cytokine storm associated with COVID-19 infection can activate C-reactive protein and calcitonin gene-related peptide (CGRP), which plays a key role in migraine pathology. The CGRP receptor antagonist vazegepant is being studied in a phase 2 clinical trial for the treatment of COVID-19–related lung inflammation.
Testing and treatment
“If I see patients with new headache, worsening headache from their baseline, or headache with systemic symptoms, I often consider screening them for COVID. If that screening is positive, I proceed with PCR testing. I also consider an MRI of the brain with and without gadolinium just to rule out any secondary causes for headache,” said Dr. Kuruvilla, noting that she has diagnosed patients with venous sinus thrombosis, ischemic stroke, and meningitis following COVID-19.
The existing literature suggests that lumbar puncture in patients with SARS-CoV-2 typically returns normal results, but Dr. Kuruvilla proceeds with it anyway with viral, bacterial, fungal, and autoimmune studies to rule out potential secondary causes for headache.
There are few studies on how to treat post–COVID-19 headache, and the general recommendation is that headache phenotype should drive treatment decisions.
In a case series, three patients with persistent headache following mild COVID-19 infection were treated with onabotulinumtoxinA and amitriptyline. They had daily headaches, along with post–COVID-19 symptoms including fatigue and insomnia. After treatment, each patient converted to episodic headaches.
One retrospective study of 37 patients found that a 5-day course of indomethacin 50 mg twice per day and pantoprazole 40 mg once per day was associated with a 50% or greater improvement in headache on the third day in 36 of the 37 patients. Five patients were free of pain by day 5.
A common problem
Neurologists have been involved in the treatment of COVID-19 since the beginning, and post–COVID-19 headache has added another layer. “It’s been a remarkably common clinical problem. And the fact that it’s actually reached the level of headache specialist actually shows that in some cases, it’s really quite a significant problem, in both its severity and persistence. So I think it’s a very, very significant issue,” said Andrew Charles, MD, professor of neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program.
Dr. Kuruvilla also discussed the question of whether neurological damage is due to direct damage from the virus, or indirect damage from an immune response. This was debated during the Q&A session following Dr. Kuruvilla’s talk, and it was pointed out that headache is a frequent side effect of the Pfizer and Moderna vaccines.
“It’s a huge open question about how much is direct invasion or damage or not even damage, but just change in function with the viral infection, as opposed to inflammation. The fact that very often the response to the vaccine is similar to what you see with COVID suggests that at least some component of it is inflammation. I wouldn’t commit to one mechanism or the other, but I’d say that it’s possible that it’s really both,” said Dr. Charles.
Dr. Kuruvilla has consulted for Cefaly, Neurolief, Theranica, Now What Media, and KX advisors. She has been on the speakers bureau for Abbvie/Allergan, Amgen/Novartis, and Lilly. She has been on advisory boards for Abbvie/Allergan, Lilly, Theranica, and Amgen/Novartis. Dr. Charles has no relevant financial disclosures.
The Centers for Disease Control and Prevention has identified it as a sentinel symptom of COVID-19 disease. “A lot of the recommendations surrounding post-COVID headache is that if you identify a patient who has headaches associated with fever, and myalgia, and other systemic symptoms, the specificity of a COVID-19 diagnosis goes up. So [COVID-19] is a really important feature to look out for in patients with headache,” Deena Kuruvilla, MD, said during a presentation on post–COVID-19 headache at the 2021 Scottsdale Headache Symposium.
Estimates of the prevalence of headache in COVID-19 range widely, from 6.5% to 71%, but Dr. Kuruvilla has plenty of personal experience with it. “During my stint on the inpatient neurology service during the peak of COVID, I saw patients with headache being one of the most frequent complaints, [along with] dizziness, stroke, and seizure among many other neurological manifestations,” said Dr. Kuruvilla, director of the Westport (Conn.) Headache Institute.
One meta-analysis showed that 47% of patients with COVID-19 complain of headache within 30 days of diagnosis, and this drops to around 10% at 60-90 days, and around 8% at 180 days.
A survey of 3,458 patients, published in the Journal of Headache Pain, found that migraine is the most common type of post–COVID-19 headache phenotype, and patients reporting anosmia-ageusia were more likely to have post–COVID-19 headache (odds ratio [OR], 5.39; 95% confidence interval, 1.66-17.45).
A case-control study of post–COVID-19 headache patients with and without a history of migraine found that those with a history of migraine were more likely to have post–COVID-19 symptoms (OR, 1.70; P < .001) and fatigue (OR, 2.89; P = .008). “Interestingly, they found no difference in headache as post-COVID symptoms in people who had a history of migraine compared with people without a history of migraine,” said Dr. Kuruvilla.
Headache and COVID-19: What is the connection?
Several mechanisms have been proposed for direct invasion of the central nervous system, either via infection through the angiotensin-converting enzyme 2 (ACE-2) receptor, which is expressed in brain regions including the motor cortex, the posterior cingulate cortex, and the olfactory bulb, among other locations. Another potential mechanism is direct entry through the olfactory nerve and the associated olfactory epithelium. There are various potential mechanisms for spread among the peripheral nervous system, and the blood-brain barrier can be compromised by infection of vascular endothelial cells. According to the literature, neuronal damage seems to occur directly from viral damage rather than from the immune response, said Dr. Kuruvilla.
The virus may also gain entry to the CNS indirectly, as a result of hypoxia and metabolic disturbances, as well as dehydration and systematic inflammation. The cytokine storm associated with COVID-19 infection can activate C-reactive protein and calcitonin gene-related peptide (CGRP), which plays a key role in migraine pathology. The CGRP receptor antagonist vazegepant is being studied in a phase 2 clinical trial for the treatment of COVID-19–related lung inflammation.
Testing and treatment
“If I see patients with new headache, worsening headache from their baseline, or headache with systemic symptoms, I often consider screening them for COVID. If that screening is positive, I proceed with PCR testing. I also consider an MRI of the brain with and without gadolinium just to rule out any secondary causes for headache,” said Dr. Kuruvilla, noting that she has diagnosed patients with venous sinus thrombosis, ischemic stroke, and meningitis following COVID-19.
The existing literature suggests that lumbar puncture in patients with SARS-CoV-2 typically returns normal results, but Dr. Kuruvilla proceeds with it anyway with viral, bacterial, fungal, and autoimmune studies to rule out potential secondary causes for headache.
There are few studies on how to treat post–COVID-19 headache, and the general recommendation is that headache phenotype should drive treatment decisions.
In a case series, three patients with persistent headache following mild COVID-19 infection were treated with onabotulinumtoxinA and amitriptyline. They had daily headaches, along with post–COVID-19 symptoms including fatigue and insomnia. After treatment, each patient converted to episodic headaches.
One retrospective study of 37 patients found that a 5-day course of indomethacin 50 mg twice per day and pantoprazole 40 mg once per day was associated with a 50% or greater improvement in headache on the third day in 36 of the 37 patients. Five patients were free of pain by day 5.
A common problem
Neurologists have been involved in the treatment of COVID-19 since the beginning, and post–COVID-19 headache has added another layer. “It’s been a remarkably common clinical problem. And the fact that it’s actually reached the level of headache specialist actually shows that in some cases, it’s really quite a significant problem, in both its severity and persistence. So I think it’s a very, very significant issue,” said Andrew Charles, MD, professor of neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program.
Dr. Kuruvilla also discussed the question of whether neurological damage is due to direct damage from the virus, or indirect damage from an immune response. This was debated during the Q&A session following Dr. Kuruvilla’s talk, and it was pointed out that headache is a frequent side effect of the Pfizer and Moderna vaccines.
“It’s a huge open question about how much is direct invasion or damage or not even damage, but just change in function with the viral infection, as opposed to inflammation. The fact that very often the response to the vaccine is similar to what you see with COVID suggests that at least some component of it is inflammation. I wouldn’t commit to one mechanism or the other, but I’d say that it’s possible that it’s really both,” said Dr. Charles.
Dr. Kuruvilla has consulted for Cefaly, Neurolief, Theranica, Now What Media, and KX advisors. She has been on the speakers bureau for Abbvie/Allergan, Amgen/Novartis, and Lilly. She has been on advisory boards for Abbvie/Allergan, Lilly, Theranica, and Amgen/Novartis. Dr. Charles has no relevant financial disclosures.
FROM 2021 SCOTTSDALE HEADACHE SYMPOSIUM