Have you ever woken up one morning with a headache that simply won’t go away? You might wonder if it was another migraine or something entirely different. Chronic headaches can be frustrating as well as disabling. It accounts for the third highest burden of disability in the world after stroke and dementia.

According to the World Health Organization (WHO) data, in 2021, approximately 3.1 billion people worldwide suffered from headache disorders. The data demonstrated that these disorders affect females more and show no significant difference among most of the age groups. 

They are considered to be one of the three most prevalent neurological disorders from childhood to old age, affecting people all over the world, irrespective of race, class, and location.¹

New daily persistent headache (NDPH) is a chronic disease of sudden onset and aggravation in the cases of patients with no history of headache. It can last up to a maximum of 3 days.

It creates chronic migraine or tension-type headaches most of the time. It may be migrainous, and therefore, one should exclude secondary causes, particularly those associated with cerebrospinal fluid (CSF) pressure or volume alterations. Most patients get relief from any migraine treatment, but for some, the experience can be persistent with treatment-resistant headaches.²

What is NDPH?

NDPH has been described in the International Classification of Headache Disorders (ICHD-3) as a headache that transforms into a continuous one within 24 hours after the onset and lasts for at least three months. Although very uncommon, it is indeed one of the most treatment-resistant and disabling primary headache disorders.

It is a relatively rare but serious condition common in adolescents and children. The pain is so sudden that patients can rarely specify a particular date. Its causative factor is not clear, but may include an inflammatory and cervicogenic role.

It is difficult to treat due to the absence of controlled trials. However, many aggressive therapies could be used, but many patients prove to be unresponsive to the standard treatment options. Thus, NDPH needs more research to ensure proper treatment conditions.³

What is chronic migraine (CM)?

Chronic migraine is a neurological disorder characterised by headache for at least 15 days per month. It shows at least 8 days of migraine characteristics. It frequently evolves from episodic migraine on the background of rising attack frequency and several risk factors, despite transforming into a separate clinical entity with its own pathophysiology. 

In comparison to episodic migraine, chronic migraine is more troublesome and is more comorbid. The mechanisms that can cause this disorder may be structural and functional brain changes, central sensitisation, and neuroinflammation. There are treatments currently available, but effectiveness is limited, and adherence is poor. For this reason, interest in novel approaches, such as neuromodulation, has sparked.⁴

Overview of the two conditions

Case studies

Case study 1: Demographic conditions

A study compared the chronic migraine (CM) and new daily persistent headache of the chronic migraine subtype (NDPH-CM) in UK and US cohorts.

For the UK group, NDPH-CM patients had a later onset, lower prevalence of migrainous symptoms, and lower family history of headache in comparison with CM. Such differences were not present among the US group. Osmophobia (a clinical marker for migraine) and older age of clinic presentation were identified as the negative predictors of NDPH-CM, and this indicates the necessity of additional NDPH-CM research, especially on clinical aspects.⁵

Case study 2: Analysis over a certain period

A retrospective study of 63 NDPH patients followed for five years showed that 35% showed migrainous features, and 65% fulfilled the ICHD-II (International Classification of Headache Disorders 2) criteria.

Though there were varying treatment responses, 37% of the patients reported excellent outcomes, while 30% of them had good responses. A significant proportion of these came from short-duration headache patients and those having identifiable triggers. In turn, intravenous therapies, including methylprednisolone and sodium valproate, were related to better outcomes, and this provoked a need for additional prospective, controlled studies.⁶

Case study 3: Comparison between the original and revised versions of NDPH

A study compared a revised definition of New Daily Persistent Headache (NDPH-R), including patients with migraine features, with the ICHD-2 criteria, which exclude them. Among 71 patients studied, 43.7% met the strict ICHD-2 criteria, while the rest had too many migraine features but shared similar clinical characteristics. The migraine-featured group (NDPH-mf) tended to be younger, more often female, and had a higher rate of depression, yet their treatment response and prognosis were comparable to those who met ICHD-2 criteria. 

Prognostic subtypes, persisting, remitting, and relapsing-remitting, were found in both groups, with the persisting type more associated with anxiety, depression, younger onset, and white race. The findings suggest that NDPH-R provides a more inclusive and clinically consistent classification, supporting its consideration for inclusion in future ICHD revisions.⁷

Headache characteristics

NDPH

• Continuity: The headache is daily and unremitting from onset
• Phenotype: NDPH can resemble either migraine or tension-type headache (TTH). In a study of 328 patients, 79.3% exhibited a migraine phenotype, while others had features akin to TTH⁸
• Variability: The intensity of the headache tends to be consistent day-to-day, lacking significant fluctuations
• Associated Features: Some patients report migrainous symptoms such as photophobia (light sensitivity), phonophobia (sound sensitivity), or mild nausea, but these are less prominent compared to CM

Chronic migraine

• Frequency: Headaches occur on 15 or more days per month, with at least eight days exhibiting migraine features
• Variability: The intensity of headaches fluctuates, sometimes causing intense pain while sometimes having relative relief
• Associated Features: CM is often accompanied by classic migraine symptoms, including throbbing pain, aura, nausea, photophobia, and phonophobia¹⁴ 
• Pain-Free Periods: Unlike NDPH, patients with CM may experience pain-free intervals between headaches

Associated symptoms

A study on NDPH reported the following symptoms as a percentage:⁹

• Photophobia in 66% of patients
• Phonophobia in 61% of patients
• Nausea in 68% of patients
• Lightheadedness in 55% of patients

Another study on chronic migraine reported the following symptoms with percentage:¹⁰

• Photophobia in 71.2%
• Phonophobia in 80.2%
• Nausea in 77.6 %
• Vomiting in 40.9%
• Osmophobia in 53.4%

Response to treatment

NDPH is characterised by resistance to routine headache remedies. Although some patients will initially react to the migraine prophylactic treatments, the long-term effectiveness is rather mixed. Thus, there isn’t any proper treatment yet.

One study found that in the first year, up to 80% of patients responded positively clinically to common migraine prophylactic treatment, but on follow-up, most patients (54%) had persistent headaches. 75% of patients got headaches in the winter months.¹¹

CM tends to respond to a variety of preventive drugs. Among those preventive treatments with well-established efficacy are topiramate, CGRP monoclonal antibodies (mAbs), and botulinum toxin A (Botox).

Combination with CGRP-targeted mAbs and Botox has been reported as useful in patients with ongoing migraine and dysfunction on one-agent preventive treatment.

The 2021 American Headache Society (AHS) consensus allows adding CGRP monoclonal antibody (mAb) treatment to one or more established preventive treatments based on clinical judgment.¹²

Underlying triggers and risk factors

NDPH is commonly seen after an infection, a stress-provoking occasion, or a mild head injury. In children, the onset is usually accompanied by physiological stress, including infection or head trauma, among others, or after surgery. In contrast to CM, NDPH does not have a defined prodrome phase.¹³

CM may be activated depending on the hormonal changes, stress, certain foods, environmental factors, and sleep disturbances. Patients may have prodrome and postdrome conditions with symptoms like changes in mood, fatigue, and cognitive deficiencies.¹⁴

Diagnostic challenges

It is challenging to distinguish NDPH from CM due to overlapping symptoms. The history of the headache and pattern recognition are very important for correct diagnosis. 

Imaging investigations, such as magnetic resonance imaging (MRI), are necessary to look for secondary causes, particularly in NDPH, where there could be coexisting entities that mimic the experience of primary headache disorders, such as idiopathic intracranial hypertension or cerebrospinal fluid leak.²

Summary

In summary, the onset, pattern of symptoms, and response to treatment of New Daily Persistent Headache (NDPH) and Chronic Migraine (CM) differ profoundly. NDPH is most frequently acute and non-remitting as a headache, whereas CM can develop in a gradual manner from episodic migraine changes.

Precise diagnosis is important for management in that the remedies that work with CM may not work well with NDPH, and misdiagnosis may result in extended disability. Due to the complexity and overlap of these conditions, consultation with a specialist in headaches is advised when a diagnosis is not straightforward or conventional therapies are unsuccessful. 

Further studies are necessary to enhance knowledge about the pathophysiology, optimise the diagnostic criteria, and come up with enhanced therapies for the two disorders (NDPH and CM) to improve patient outcomes.

FAQs

Is NDPH serious?

Yes, NDPH is serious, especially because it usually comes on suddenly and becomes persistent with no remission. It may have a great influence on the quality of life due to chronic pain and accompanying symptoms such as sensitivity to light or sound. Although not commonly life-threatening, it is difficult to treat and might require chronic management, affecting your day-to-day activities.

Is NDPH an autoimmune disease?

NDPH cannot be regarded as an autoimmune disorder. However, there are studies that conclude, in some cases, it could have an immune-associated or inflammatory component, particularly when occurring after a prior infection. The exact cause of NDPH is not fully known, and it most likely differs between people.

At what point are migraines chronic?

If a person has a headache for at least 15 days a month for at least three months, migraines are said to be chronic. Of them, at least 8 days must be dedicated to migraine characteristics such as throbbing pain, nausea, or light and sound sensitivity. This condition is called chronic migraine and usually requires special treatment.