Introduction

New Daily Persistent Headache (NDPH) is a unique and often debilitating primary headache disorder marked by the abrupt onset of unremitting daily headache that continues for months or even years. Unlike episodic headache types such as migraine or tension-type headache, NDPH is continuous from the very beginning and lacks remission. What makes NDPH even more challenging is its frequent emergence following viral illnesses (e.g., Epstein-Barr virus [EBV], influenza) or stressful life events.¹ Increasing attention has been paid to the link between NDPH and post-viral syndromes, including long COVID-19, post-EBV fatigue syndrome, and post-influenza neurological sequelae.^{2, 3, 11} Individuals recovering from these infections often report persistent neurological symptoms, with headaches being among the most common complaints.¹² Understanding this overlap between persistent headaches and long-term viral effects is critical for both diagnosis and long-term patient care.

What is a new daily persistent headache NDPH?

The classification of NDPH was initially established by the International Headache Society in 2004. It is diagnosed primarily based on patient history, with criteria requiring the headache to start on a specific day, to persist daily from onset, and to be present for at least three months without remitting.¹ Clinical features can vary: some individuals experience a dull, tension-type pain while others describe a throbbing sensation more akin to migraines. Unfortunately, treatment is often ineffective, and conventional therapies for migraines or tension headaches frequently offer little relief.⁴

Studies show that a significant subset of NDPH patients recall a triggering viral illness or upper respiratory infection before headache onset.^{1, 4} This temporal association has led researchers to investigate the immunological and neurological changes following viral infections that may contribute to NDPH development.

Post-viral syndromes and headache

Post-viral syndrome refers to the prolonged symptoms that occur after recovery from acute viral infections, including EBV, influenza, dengue, and SARS-CoV-2.^{2, 11, 13} These may include fatigue, cognitive difficulties, muscle aches, and persistent headaches.^{2, 12} A 2021 study found that 20% of EBV-associated mononucleosis patients developed chronic headaches lasting >6 months, while 10–15% of influenza survivors reported similar persistence.¹² The COVID-19 pandemic highlighted this phenomenon, with 30–50% of long COVID patients citing headache as a dominant symptom.³

The underlying mechanisms may involve immune dysregulation, persistent inflammation, or direct neurotropic effects. For example, EBV can trigger latent neural inflammation,¹¹ while the dengue virus disrupts the blood-brain barrier.¹³

The cervical connection: structural and functional perspectives

Emerging evidence suggests that cervical spine dysfunction may influence or exacerbate post-viral headaches, including NDPH. Cervical spine joint hypermobility, for instance, has been proposed as a possible risk factor for developing NDPH, especially in individuals predisposed to mechanical neck strain⁷. Abnormalities in neck alignment or persistent cervical tension might alter neural signalling and pain modulation, potentially maintaining headache persistence after the acute viral phase resolves.

Virus-Specific Cervical Patterns (Key Exam Findings):

• Post-COVID-19 Cases: Patients frequently show signs of stiffness in the upper cervical spine (C1-C3) along with myofascial trigger points, potentially as a result of extended bed rest or stress from intubation^{5, 10}
• Post-EBV Cases: More frequently involve lymphadenopathy-associated cervical tension, particularly in the sternocleidomastoid and suboccipital regions¹¹
• Shared Mechanism: Both viruses may sensitise the trigeminocervical complex, converging pain signals from neck and meningeal structures^{7, 10}

Research also supports the notion that tension-type headaches and cervicogenic headaches share overlapping pathways with NDPH. These headaches often originate from structural or muscular issues in the neck, including cervical facet joint irritation and dysfunction in cervical proprioception.^{8, 9}

Key Exam notes:

• Check for tenderness at the C2-C3 spinal joints (found in 62% of NDPH patients) and test neck movement^{7, 10}
• Imaging: While not routinely required, MRI may reveal inflammatory changes in cervical ligaments post-COVID-19⁵

Musculoskeletal assessments of individuals with chronic headaches show increased tenderness in the cervical region and impaired cervical movement control. A study indicated that individuals with tension-type headaches commonly display impairments in the cervical spine, implying that peripheral nociceptive signals may contribute to the ongoing central sensitisation and the chronic nature of their headaches ¹⁰.

Treatment Implications:

• Manual Therapy: Cervical mobilisation improves outcomes in 45% of post-viral NDPH cases¹⁰
• Exercise: Proprioception retraining (e.g., head-eye coordination) reduces headache frequency by 30%¹⁰

Thus, a post-viral headache, whether triggered by immune dysregulation or cervical imbalance, may persist if these structural and functional issues are not identified and addressed.

Viral triggers of NDPH: understanding links from covid-19 and other sources

The emergence of COVID-19 has provided a wealth of clinical observations linking viral infection to new-onset persistent headaches. Individuals recovering from COVID-19 can experience NDPH-like symptoms, even without a previous history of headache.^{5, 6}

Interestingly, these patients often describe their headaches as beginning during the viral illness and persisting without fluctuation, consistent with the clinical picture of NDPH. Some clinicians believe that the sheer immune response generated by COVID-19 may be responsible for initiating long-lasting inflammation in the meninges or trigeminal system structures closely involved in pain processing.⁵

One case series documented patients who developed daily headache symptoms within days of COVID-19 onset and reported persistence for over three months. Treatments such as corticosteroids and anti-inflammatory agents provided mixed results, highlighting the challenge of managing post-viral headache syndromes.^{3, 5}

While COVID-19 offers recent insights, other viruses such as Epstein-Barr virus (EBV) and influenza also trigger NDPH. Key differences include:

• EBV: Post-infectious headaches often begin weeks after recovery, coinciding with fatigue and cervical lymphadenopathy¹¹. In contrast, COVID-19-related headaches typically emerge during acute infection^{3, 5}
• Influenza: Post-viral headaches are frequently shorter-lived (6–12 months) but share similar inflammatory markers (e.g., elevated IL-6) with COVID-19 cases¹²
• Shared Mechanisms: Both COVID-19 and EBV may cause persistent neuroinflammation, while influenza’s effects are often transient^{5, 11, 12}

Notably, cervical spine dysfunction (e.g., C1-C3 joint irritation) is a common thread across post-viral NDPH, regardless of the triggering virus.^{7, 10}

Management and prognosis

Treating NDPH remains difficult, as there is no universally effective therapy. Management often involves a trial-and-error approach, combining pharmacological interventions like tricyclic antidepressants, muscle relaxants, or anti-inflammatories with non-pharmacological options such as physical therapy, stress reduction, and cognitive behavioural therapy.^{1, 6}

Virus-Specific Considerations:

• Post-EBV Cases: Similar to other post-viral syndromes (e.g., COVID-19, influenza), EBV-associated headaches may persist due to neuroinflammation¹¹ or cervical spine dysfunction linked to lymphadenopathy^{8, 9}
• Post-COVID Cases: Low-dose naltrexone (LDN) shows promise for immune-related headaches^{3, 5}
• Post-Influenza Cases: Often resolve faster (6–12 months) with standard therapies¹²

For individuals with suspected cervicogenic contribution, targeted physiotherapy or manual therapy addressing cervical spine alignment and muscular imbalances may provide relief.^{9, 10} Identifying coexisting issues such as anxiety, poor sleep hygiene, and autonomic dysregulation can also help improve outcomes.

For patients recovering from viral illnesses (e.g., COVID-19, EBV), a multidisciplinary strategy (neurologists, physiotherapists, and psychologists) is most effective. Addressing both neurological and musculoskeletal components improves recovery rates by 40% compared to single-modality care.^{3, 10}

Prognosis varies by trigger:

• EBV-associated NDPH: Often persists >2 years¹¹
• Post-influenza NDPH: Typically resolves within 1 year¹²
• Post-COVID NDPH: 50% remission at 18 months³

Some individuals experience spontaneous remission within 1–2 years, while others may continue to experience symptoms indefinitely.⁴ Early intervention, particularly when post-viral headache patterns are recognised promptly, may reduce chronicity risk.

Conclusion

The relationship between NDPH and post-viral syndromes, particularly in the wake of COVID-19, highlights the need for comprehensive patient evaluation and multidisciplinary care. With growing evidence supporting links between cervical spine dysfunction, viral immune response, and chronic headache mechanisms, a tailored approach addressing the viral history, musculoskeletal issues, and nervous system involvement is essential. A better understanding of NDPH and its possible post-viral triggers offers hope for improved treatments and long-term outcomes.