key: cord-0802627-r8ow4nbc
authors: Simmons, Adrienne; Bonner, Alexandra; Giel, Ashley; Pezzano, Alexandra; Rothner, A. David
title: Probable New Daily Persistent Headache after COVID-19 in Children and Adolescents
date: 2022-04-28
journal: Pediatr Neurol
DOI: 10.1016/j.pediatrneurol.2022.04.009
sha: 45fda1a9380404e437fc7abebfc2b44e54aad522
doc_id: 802627
cord_uid: r8ow4nbc

Headache has been cited as both a primary symptom and a sequela of infection with the novel coronavirus. Cases of Long COVID Headache have already been documented in adults, but literature on similar cases in children and adolescents is scant. We present 3 cases of persistent headache after infection with COVID-19 in pediatric patients presenting to a tertiary headache center. Infection has been suggested as a trigger for chronic headaches, specifically those of the New Daily Persistent Headache type. Though the association between New Daily Persistent Headache and COVID-19 remains unclear, these cases highlight the importance of awareness of the neurological sequelae of novel coronavirus infection in children and adolescents.

Though respiratory symptoms are the predominant symptoms of infection with COVID-19, systemic symptoms such as fever, myalgias and headache also appear in both adult and pediatric patients. Headache has been described as both a symptom of current infection and one that persists after clearance of the virus 1,2 . However, there is little literature on persistent headache after COVID-19 infection in children and adolescents. Here, we describe the cases of 3 pediatric patients who presented with probable NDPH symptoms after contracting COVID-19.

The first patient was a 15-year-old girl who was diagnosed with COVID-19 by nasopharyngeal swab after 7 days of headache, extremity numbness, fatigue, and neck pain. Prior to diagnosis, her only comorbid condition was depression, treated with Lexapro. She did not have a prior personal or family history of headache disorder, nor did she have a history of headache-related episodic syndromes. She experienced persistent headaches after resolution of COVID-19 symptoms that were described as a bitemporal pressure without radiation. The headaches were sometimes pounding in nature, were accompanied by neck tightness, and occurred almost daily. Treatment included a combination drug of acetaminophen, aspirin, and caffeine or ibuprofen for rescue medications, and lifestyle modifications such as sleep hygiene, adequate water intake, limiting screen time, and limiting caffeine products. This patient's headaches continued for almost 7 months after diagnosis of COVID-19 and she is still receiving follow-up care.

The second patient was a 16-year-old male who presented for evaluation of approximately 8 months of daily headache. Headache onset in January 2021 with associated congestion. He tested positive for Covid-19 via nasal swab at the time of symptoms, after family contacts tested positive. Ultimately congestion improved with persistence of the headache. The headache was described as bilateral fronto-temporal throbbing and pulling with associated lightheadedness with position changes that persisted throughout the day with some improvement in the morning and worsening in the evening to an average of 7/10 pain intensity. Verapamil was ineffective in improving his symptoms. Acupuncture, chiropractic medicine and massage therapy were also ineffective in improving his symptoms. OTC abortive therapies were minimally effective in symptom improvement. This patient had a history of dull constant frontal headache of 4/10 severity after a concussion with no associated episodic syndromes, which lasted approximately 6 months. The onset of his post-concussion headache was one year prior to the onset of this presenting headache. His headache history was otherwise negative. The patient's mother and sister both have migraines. After evaluation, Verapamil was tapered off and a prednisone course was initiated. Re-evaluation was scheduled for 3 months after the initial visit.

The third patient was a previously healthy 10-year-old girl with a COVID-19-positive sick contact. Her symptoms included anosmia, nasal congestion, rhinorrhea, headache, and decreased appetite. Two days after symptom onset, she was diagnosed with COVID-19 by nasopharyngeal swab. Two months later, she had complaints of a daily headache that had lasted for approximately 2 weeks. Her headaches occurred almost every afternoon and presented as a J o u r n a l P r e -p r o o f bilateral pressure behind the eyes. Each headache lasted about an hour and was associated with photophobia, dizziness, and occasionally, blurred vision. The headaches improved with lying down and were worsened with online activities, movement, and dehydration. The patient was treated with a combination drug of butterbur, petasin, isopetasin, riboflavin, magnesium, and coenzyme Q10 as a preventative measure and she used acetaminophen and ibuprofen for rescue medicines. She was also encouraged to keep a headache diary and make lifestyle modifications such as drinking water, avoiding frequent over-the-counter pain medications, and practicing good sleep hygiene. These headaches lasted for a duration of at least two months, thought the patient could not recall the exact duration. At 5 month follow up, the patient reported that her headaches were "resolved", though on a follow-up phone call 14 months after headache onset, she endorsed continued intermittent tension-type headaches that she does not treat. Prior to this, she had no history of headache, episodic syndrome, or any other medical condition. The patient's mother did have a history of migraine and tension-type headaches.

New daily persistent headache (NDPH) was first described by Dr. Walter Vanast in 1986 as a self-limiting and benign headache disorder 3 . The International Classification of Headache Disorders (ICHD) requires the headaches to be persistent, daily, and with a clearly remembered start 4 . They can have either migraine-like or tension-type-like features, but must be present for at least 3 months 4 . The usual presentation involves bilateral, non-pulsating headaches that are not aggravated by routine physical activity 5 . They may be accompanied by photophobia, phonophobia, nausea, or vomiting 5 . A number of patients also experience sleep disturbance, visual disturbance, fatigue, fatigue among other comorbid symptoms 5 .

Within the pediatric population, NDPH occurs more frequently in females, and its start may correlate with stress from school or infection 6 . These headaches have classically been challenging to treat. They are often refractory to treatment and/or unremitting. Treatment methods have included preventative drugs such as topiramate and amitriptyline; rescue drugs such as ibuprofen or acetaminophen; non-pharmacotherapy such as acupuncture, psychotherapy, and biofeedback; and lifestyle modifications such as regular sleep and diet, avoiding school absences, and limiting over-the-counter medications 5, 6 . No pharmacological treatment is one of the indicators of a poor prognosis for the condition. Approximately 50% of children and adolescents have either complete resolution or reduced frequency of headache within a year of symptom onset 6 . Clinicians and researchers must take into account that headaches of this type are rare, occurring in approximately 0.1% of the population, but they are more prevalent in children and adolescents 5 .

In contrast, the novel coronavirus (COVID-19) has become widespread, affecting millions of people since its identification in January 2020. Though infection and illness are common in adults, children are less likely to become severely ill than their adult counterparts. In children, the illness presents primarily with fever and cough. Other common symptoms include fatigue, myalgia, rhinorrhea, anosmia, and headache 1 . Studies suggest that headache is less likely to occur in children and adolescents than symptoms such as fever and cough, occurring in 10-20% of pediatric COVID-19 cases 7 . Despite this, there are already some accounts of adults with J o u r n a l P r e -p r o o f headache as a symptom of Long COVID, a set of symptoms that patients' may experience for months after their infection 2 . This headache may be accompanied by "brain fog", poor cognition and memory, and worsening of migraines in patients with such history. The headache has been reported as occurring for up to 6 months after discharge from hospitalization for COVID-19 2 . An Italian study reported two cases of women with a diagnosis of probably NDPH after confirmed COVID infection. Both women were in their 40s and experienced persistent headache for at least 20 days after their headache onset 8 . There are been no similar accounts documented in children.

The distinction between Long COVID headache and NDPH has yet to be explored. Headaches occurring as a manifestation of Long COVID syndrome may have many pathophysiological causes, including neuronal invasion of the virus, hypoxia-mediated damage, and cytokine storm 2 . The pathophysiology of NDPH remains unclear, though there are many widely recognized triggers. The link between infection and NDPH first became apparent when multiple patients with NDPH were found positive for Epstein-Barr virus 9 . Rozen also noted that there have been many historical cases for of new persistent headache after pandemics 10 . While these were noted before the classification of NDPH, Rozen also warned of the potential for NDPH to become a sequalae of COVID-19 infection based on this historical context and documentation of headache as a primary symptom of COVID-19 10 . It is still unclear how probable NDPH presentations occurring after COVID-19 will play out in patients, however these three cases show a temporal association between the virus and headaches of NDPH character. While it is possible that these patients had Long COVID symptoms, or more general infection triggered headaches, these cases align with the ICHD definition of NDPH. As such, they are probable cases of NDPH, especially when considered in the context of literature highlighting the association between viral illness and NDPH. Additionally, these cases draw attention to the importance of awareness of the neurological sequelae of COVID-19 infection in the pediatric population.

The Authors declare that there is no conflict of interest.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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