New daily persistent headache

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New daily persistent headache

New daily persistent headache (NDPH) is a primary headache syndrome which can mimic chronic migraine and chronic tension-type headache. The headache is daily and unremitting from very soon after onset (within 3 days at most), usually in a person who does not have a history of a primary headache disorder. The pain can be intermittent, but lasts more than 3 months. Headache onset is abrupt and people often remember the date, circumstance and, occasionally, the time of headache onset. One retrospective study stated that over 80% of patients could state the exact date their headache began.[1]

The cause of NDPH is unknown, and it may have more than one etiology. NDPH onset is commonly associated with an infection or flu-like illness, stressful life event, minor head trauma, and extra cranial surgery. Infection or flu-like illness and stressful life event are most often cited.[1] The pathophysiology of NDPH is poorly understood.

The syndrome is difficult to treat and may persist for years. The age of onset ranges from 6 to greater than 70 years old, with a mean of 35 years. It is found to be more common in females in both the adult and pediatric populations. NDPH is rare. The Akershus study of chronic headache, a population based cross sectional study of 30,000 persons aged 30–44 years in Norway, found a one-year prevalence of 0.03 percent in the population.[2]

In 1986, Vanast was the first author to describe the new daily-persistent headache (NDPH) as a benign form of chronic daily headache (CDH).[3] The criteria for the diagnosis of NDPH were proposed in 1994 (the Silberstein–Lipton criteria)[4] but not included in the International Classification of Headache Disorders (ICHD) until 2004.

Signs and symptoms

The headaches can vary greatly in their clinical presentation and duration.[citation needed]

Quality of the headache has been described as dull and/or pressure-like sensation, and throbbing and/or pulsating sensation. The pain is usually on both sides of the head (in 88–93% of people with NDPH), but may be unilateral, and may be localized to any head region.[5] The pain can fluctuate in intensity and duration, is daily, and lasts more than 3 months.[citation needed]

There may be accompanying photophobia, phonophobia, lightheadedness or mild nausea. Co-morbidity with mood disorders has been reported in a subset of patients.[citation needed]

Cranial autonomic nervous symptoms occur with painful exacerbations in 21%, and cutaneous allodynia may be present in 26%.[6]

In 2002, Li and Rozen[1] conducted a study of 56 patients at the Jefferson Headache Center in Philadelphia and published the following results:

  • 82% of patients were able to pinpoint the exact day their headache started.
  • 30% of the patients, the onset of the headache occurred in correlation with an infection or flu-like illness.
  • 38% of the patients had a prior personal history of headache.
  • 29% of the patients had a family history of headache.
  • 68% reported nausea.
  • 66% reported photophobia.
  • 61% reported phonophobia.
  • 55% reported lightheadedness.

Imaging and laboratory testing were unremarkable except for an unusually high number of patients who tested positive for a past Epstein-Barr virus infection.[citation needed]


The pathophysiology of NDPH is poorly understood. Research points to an immune-mediated, inflammatory process. Cervical joint hypermobility and defective internal jugular venous drainage have also been suggested as causes.[7][8]

In 1987, Vanast first suggested autoimmune disorder with a persistent viral trigger for CDH (now referred to as NDPH).[9] Post-infectious origins have been approximated to make up anywhere between 30 and 80% of NDPH patients in different studies. Viruses that have been implicated include Epstein-Barr virus, herpes simplex virus and cytomegalovirus.[10][11]

Non-specific upper respiratory infections including rhinitis and pharyngitis are most often cited by patients.[12] In one study, 46.5% patients recalled a specific trigger with a respiratory tract illness being the most common. In children, almost half report headache onset during an infection.

A study by Rozen and Swindan in 2007 found elevated levels of tumor necrosis factor alpha, a proinflammatory cytokine, in the cerebrospinal fluid but not the blood of patients with NDPH, chronic migraine, and post-traumatic headaches suggesting inflammation as the cause of the headaches.[13]

NDPH as an inflammatory, post-infectious manifestation indicates a potential meningoencephalitis event in NDPH patients. Tissue specificity is a general feature of post-infectious, immune-mediated conditions, and the meninges are a type of connective tissue membrane. Inflammation of the meninges was first proposed as a possible pathophysiology for migraine in the 1960s and has recently been explored again.[14] This hypothesis is based on meningeal mast cell activation. Reactive arthritis (ReA) is a post-infectious disease entity of synovium/joints with connective tissue membrane (synovial membrane of the joints) which provides a corollary.

NDPH has been reported in Hashimoto's encephalopathy, an immune-mediated type of encephalitis.[15] A mean 5-year retrospective analysis of 53 patients with a history of viral meningitis and 17 patients with a history of bacterial meningitis showed an increased onset of subsequent new onset headache and increased severity of those with prior primary headaches.[16]


Although NDPH is classified as a primary headache syndrome, it must be remembered that a number of important conditions can present with a new-onset persisting headache, and these must be excluded prior to making a diagnosis of a primary headache disorder.[citation needed]

Differential diagnosis

a,b)New daily persistent headache with isolated sphenoiditis[17][18]

The diagnosis is one of excluding the many secondary types or NDPH mimics, which is especially critical early in the course of the disease when a secondary etiology is more likely. NDPH mimics include but are not limited to:[citation needed]

Many doctors state that the condition is best viewed as a syndrome rather than a diagnosis.[19] Once a diagnosis of NDPH is made, clinicians argue that patients are best managed according to the more detailed pathophysiology-based diagnosis than lumped together into a single group, since a single disorder is unlikely to exist.[citation needed]


NDPH is classified as a Primary Headache Disorder by the ICHD-2 classification system (by the IHS) using number 4.8. It is one of the types of primary headache syndromes that present as a chronic daily headache, which is a headache present for more than 15 days a month for more than 3 months.[citation needed]

ICHD criteria

The ICHD diagnostic criteria are:[20]

  1. Headache that, within 3 days of onset, fulfils criteria 2-4
  2. Headache is present daily, and is unremitting, for > 3 months
  3. At least two of the following pain characteristics:
    1. bilateral location
    2. pressing/tightening (non-pulsating) quality
    3. mild or moderate intensity
    4. not aggravated by routine physical activity such as walking or climbing
  4. Both of the following:
    1. no more than one of photophobia, phonophobia or mild nausea
    2. neither moderate or severe nausea nor vomiting
  5. Not attributed to another disorder


  1. Headache may be unremitting from the moment of onset or very rapidly build up to continuous and unremitting pain. Such onset or rapid development must be clearly recalled and unambiguously described by the patient. Otherwise it is coded as 2.3 chronic tension-type headache.
  2. History and physical and neurological examinations do not suggest any of the disorders listed in groups 5-12 (including 8.2 medication overuse headaches and its subforms), or history and/or physical and/or neurological examinations do suggest such disorder but it is ruled out by appropriate investigations, or such disorder is present but headache does not occur for the first time in close temporal relation to the disorder.

Criteria revision

Although the original Silberstein–Lipton criteria and the original description by Vanast make no suggestion for the exclusion of migrainous features in NDPH, the current ICHD criteria exclude patients with migrainous features. When migraine features are present, classification thus becomes problematic.

It has been reported that migraine symptoms may be present in over 50% of NDPH patients.[21] The current criteria definition thus excludes more than half of patients with new onset of daily headache. This exclusion due to migrainous features could have adverse scientific, diagnostic, and treatment consequences.[22]

One proposal for reclassification of the criteria is from a study conducted on retrospective analysis of the records of 1348 patients regularly treated at the headache clinic of the Department of Neurology of Santa Casa de São Paulo, Brazil, and would be the following subdivision: NDPH with migraine features and without migraine features that would allow the inclusion of all individuals present who has a daily and persistent headache from the beginning.[23]

Another proposed reclassification of the criteria is from a study conducted as a retrospective chart review of patients seen at the Headache Center at Montefiore Medical Center in Bronx, New York, from September 2005 to April 2009. The revised criteria for NDPH definition does not exclude migraine features (NDPH-R), and three subdivisions were created and described based on prognosis: Persisting, remitting, and relapsing–remitting. Additionally, this revised criteria would not include parts C or D currently required by the ICHD diagnostic criteria for NDPH.[6]


There is no specific treatment for NDPH.[24] Often they are treated similar to migraines.[24]

A number of medications have been used including amitriptyline, gabapentin, pregabalin, propranolol, and topiramate.[25][26] There are no prospective placebo controlled trials of preventive treatment. In those with migrainous features treatment may be similar to migraines.[27]

Opiates, or narcotics, tend to be avoided because of their side effects, including the development of medication overuse headaches and potential for dependency. NDPH is often associated with medication overuse.[2] To avoid the development of medication overuse headaches, it is advised not to use pain relievers for more than nine days a month.

NDPH, like other primary headaches, has been linked to comorbid psychiatric conditions, mainly mood and anxiety and panic disorders. The spectrum of anxiety disorders, particularly panic disorder, should be considered in NDPH patients presenting with psychiatric symptoms. Simultaneous treatment of both disorders may lead to good outcomes.[28]

Medications within the tetracycline family, mexiletine, corticosteroids and nerve blocks are being studied.[24] Occipital nerve block have been reported to be helpful for some people. 23/71 people had undergone a nerve block for their severe headache. The NDPH-ICHD group responded to the nerve block much more often (88.9%) than the NDPH with migraine features (42.9% responded to nerve block).[5]


Most patients have persistent headaches, although about 15% will remit, and 8% will have a relapsing-remitting type.[21] It is not infrequent for NDPH to be an intractable headache disorder that is unresponsive to standard headache therapies.


  1. 1.0 1.1 1.2 Li, D; Rozen, TD (2002). "The clinical characteristics of new daily persistent headache". Cephalalgia. 22 (1): 66–9. doi:10.1046/j.1468-2982.2002.00326.x. PMID 11993616. S2CID 22449935.
  2. 2.0 2.1 Grande, RB; Aaseth, K; Lundqvist, C; Russell, MB (2009). "Prevalence of new daily persistent headache in the general population. The Akershus study of chronic headache". Cephalalgia. 29 (11): 1149–55. doi:10.1111/j.1468-2982.2009.01842.x. PMID 19830882. S2CID 24240448.
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  4. Silberstein, Stephen D.; Lipton, Richard B.; Solomon, Seymour; Mathew, Ninan T. (1994). "Classification of Daily and Near-Daily Headaches: Proposed Revisions to the IHS Criteria". Headache: The Journal of Head and Face Pain. 34 (1): 1–7. doi:10.1111/j.1526-4610.1994.hed3401001.x. PMID 8132434. S2CID 43292571.
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  6. 6.0 6.1 Robbins, M. S.; Grosberg, B. M.; Napchan, U.; Crystal, S. C.; Lipton, R. B. (2010). "Clinical and prognostic subforms of new daily-persistent headache". Neurology. 74 (17): 1358–64. doi:10.1212/WNL.0b013e3181dad5de. PMC 3462554. PMID 20421580.
  7. Rozen, TD; Roth, JM; Denenberg, N (2006). "Cervical spine joint hypermobility: A possible predisposing factor for new daily persistent headache". Cephalalgia. 26 (10): 1182–5. doi:10.1111/j.1468-2982.2006.01187.x. PMID 16961783. S2CID 25434393.
  8. Donnet, A.; Metellus, P.; Levrier, O.; Mekkaoui, C.; Fuentes, S.; Dufour, H.; Conrath, J.; Grisoli, F. (2008). "Endovascular treatment of idiopathic intracranial hypertension: Clinical and radiologic outcome of 10 consecutive patients". Neurology. 70 (8): 641–7. doi:10.1212/01.wnl.0000299894.30700.d2. PMID 18285539. S2CID 30729677.
  9. Vanast, W.J.; Diaz-Mitoma, F.; Tyrrell, D.L.J. (1987). "Hypothesis: Chronic Benign Daily Headache is an Immune Disorder with a Viral Trigger". Headache: The Journal of Head and Face Pain. 27 (3): 138–42. doi:10.1111/j.1526-4610.1987.hed2703138.x. PMID 3036747. S2CID 937845.
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  11. Meineri, P.; Torre, E.; Rota, E.; Grasso, E. (2004). "New daily persistent headache: Clinical and serological characteristics in a retrospective study". Neurological Sciences. 25: S281–2. doi:10.1007/s10072-004-0310-8. PMID 15549561. S2CID 33561625.
  12. Prakash, Sanjay; Patel, Niyati; Golwala, Purva; Patell, Rushad (2011). "Post-infectious headache: A reactive headache?". The Journal of Headache and Pain. 12 (4): 467–73. doi:10.1007/s10194-011-0346-0. PMC 3139051. PMID 21544648.
  13. Rozen, Todd; Swidan, Sahar Z. (2007). "Elevation of CSF Tumor Necrosis Factor α Levels in New Daily Persistent Headache and Treatment Refractory Chronic Migraine". Headache: The Journal of Head and Face Pain. 47 (7): 1050–5. doi:10.1111/j.1526-4610.2006.00722.x. PMID 17635596. S2CID 24890908.
  14. Levy, Dan (2009). "Migraine pain, meningeal inflammation, and mast cells". Current Pain and Headache Reports. 13 (3): 237–40. doi:10.1007/s11916-009-0040-y. PMID 19457286. S2CID 21309926.
  15. Jacome, Daniel (13 October 2010). "New Daily Persistent Headache As A Presenting Symptom Of Hashimoto's Encephalopathy". Webmed Central. Archived from the original on 17 September 2013. Retrieved 22 December 2012. {{cite journal}}: Cite journal requires |journal= (help)
  16. Neufeld, Miriam Y.; Treves, Therese A.; Chistik, Vladimir; Korczyn, Amos D. (1999). "Postmeningitis Headache". Headache: The Journal of Head and Face Pain. 39 (2): 132–134. doi:10.1046/j.1526-4610.1999.3902132.x. PMID 15613206. S2CID 45280694.
  17. Baron, Eric P.; Rothner, A. David (March 2010). "New daily persistent headache in children and adolescents". Current Neurology and Neuroscience Reports. 10 (2): 127–132. doi:10.1007/s11910-010-0097-3. ISSN 1534-6293. Retrieved 15 September article
  18. Lee, Jeongho; Rhee, Minhee; Suh, Eun Sook (2015). "New daily persistent headache with isolated sphenoiditis in children". Korean Journal of Pediatrics. 58 (2): 73–76. doi:10.3345/kjp.2015.58.2.73. ISSN 1738-1061. Retrieved 15 September 2022.Case report which cites aforementioned review #17(Baron EP, Rothner AD. New daily persistent headache in children and adolescents. Curr Neurol Neurosci Rep. 2010;10:127–132)....."Isolated sphenoid sinusitis is rare in children and is usually misdiagnosed because of its atypical manifestations. Thus, suspicion is required when assessing children with NDPH or atypical headache without migraine history or visual symptoms"
  19. Goadsby, Peter J. (2011). "New Daily Persistent Headache: A Syndrome Not a Discrete Disorder". Headache: The Journal of Head and Face Pain. 51 (4): 650–3. doi:10.1111/j.1526-4610.2011.01872.x. PMID 21457252. S2CID 23180896.
  20. "Archive copy". Archived from the original on 2016-05-20. Retrieved 2022-07-04.{{cite web}}: CS1 maint: archived copy as title (link)[full citation needed]
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  23. Monzillo, Paulo Hélio; Nemoto, Patrícia Homsi (2011). "Patients with sudden onset headache not meeting the criteria of the International Headache Society for new daily persistent headache. How to classify them?". Arquivos de Neuro-Psiquiatria. 69 (6): 928–31. doi:10.1590/S0004-282X2011000700016. PMID 22297882.
  24. 24.0 24.1 24.2 Rozen, TD (July 2014). "New daily persistent headache: an update". Current Pain and Headache Reports. 18 (7): 431. doi:10.1007/s11916-014-0431-6. PMID 24820732. S2CID 40617119.
  25. Mack, KJ (February 2009). "New daily persistent headache in children and adults". Current Pain and Headache Reports. 13 (1): 47–51. doi:10.1007/s11916-009-0010-4. PMID 19126371. S2CID 41412372.
  26. Evans, Randolph W.; Seifert, Tad D. (2011). "The Challenge of New Daily Persistent Headache". Headache: The Journal of Head and Face Pain. 51 (1): 145–154. doi:10.1111/j.1526-4610.2010.01812.x. PMID 21198576.
  27. Tyagi, Alok (2012). "New daily persistent headache". Annals of Indian Academy of Neurology. 15 (5): 62–5. doi:10.4103/0972-2327.100011. PMC 3444222. PMID 23024565.
  28. Peres, M. F.; Lucchetti, G.; Mercante, J. P.; Young, W. B. (2010). "New daily persistent headache and panic disorder". Cephalalgia. 31 (2): 250–3. doi:10.1177/0333102410383588. PMID 20851838. S2CID 24820588.

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