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 »  History of Ndph ...
 » Clinical Features
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Table of Contents    
Year : 2018  |  Volume : 66  |  Issue : 3  |  Page : 679-687

New daily persistent headache: An evolving entity

1 Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India
2 Department of Neurology, SGPGIMS, Raebareli Road, Lucknow, Uttar Pradesh, India
3 Department of Internal Medicine, Maimonides Medical Center, New York City, USA

Date of Web Publication15-May-2018

Correspondence Address:
Dr. Vimal Kumar Paliwal
Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow - 226 014, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.232291

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 » Abstract 

New daily persistent headache (NDPH) is characterized by an abrupt onset of headache that becomes a daily entity, is unremitting and continuous from the onset, and lasts for more than 3 months. Dr Walter Vanast first described NDPH in the year 1986. Originally, it was proposed as a chronic daily headache but it was placed under “other primary headaches” in the International Classification of Headache Disorder Second Edition (ICHD 2nd edition). However, with evolving literature and better understanding of its clinical characteristics, it was classified as a “chronic daily headache” in the ICHD 3rd edition beta. There are still many knowledge-gaps regarding the underlying cause, pathophysiology, natural history and treatment of NDPH. This review tries to revisit the entity and discusses the current status of understanding regarding NDPH.

Keywords: Chronic daily headache, chronic migraine, chronic tension type headache, hemicrania continua, low cerebrospinal fluid pressure headache, new daily persistent headache
Key Message:
New daily persistent headache (NDPH) is characterized by an abrupt onset of headache that becomes daily, is unremitting and continuous from the onset, and lasts for more than 3 months. This article reviews the clinical spectrum of this disorder.

How to cite this article:
Uniyal R, Paliwal VK, Anand S, Ambesh P. New daily persistent headache: An evolving entity. Neurol India 2018;66:679-87

How to cite this URL:
Uniyal R, Paliwal VK, Anand S, Ambesh P. New daily persistent headache: An evolving entity. Neurol India [serial online] 2018 [cited 2022 May 25];66:679-87. Available from: https://www.neurologyindia.com/text.asp?2018/66/3/679/232291

New daily persistent headache (NDPH) is a relatively new headache type. It was grouped among “other primary headaches” in the International Classification of Headache Disorders (ICHD II). Recently, however, NDPH has gained entry into the group of “chronic daily headaches” in the new ICHD III beta.[1],[2] NDPH is now placed along with chronic tension type headache, chronic migraine, and hemicrania continua.[2] NDPH is characterized by an abrupt or acute onset of headache followed by a daily, unremitting and continuous course for more than 3 months.[2] The onset of NDPH is so dramatic that majority of patients remember the date or month or at least the circumstances that have led to the onset of their headache. The onset of headache is so dramatic that majority of patients remember the date or month of onset of headache or at least they remember the circumstances that caused it.[3],[4],[5],[6],[7],[8] Some patients with NDPH report triggers prior to the onset of headache but none of the triggers seem to have a cause-to-effect relationship with NDPH.[3],[4],[6],[7],[8],[9],[10] NDPH is recognized as one of the most treatment-refractory headaches. However, a subset of patients with NDPH may have spontaneous remission. With more awareness and research, the understanding regarding NDPH is gradually evolving and, therefore, the present review aims to summarize the current status of understanding regarding this entity.

 » History of Ndph and Evolution of Its Diagnostic Criteria Top

Dr. Walter Vanast first described NDPH in the year 1986.[11] He presented a case series of 45 patients at the 28th annual meeting of the American Association for the Study of Headache (now recognized as the American Headache Society). However, the first International Classification of Headache Disorders (ICHD) that was published in 1988 did not include NDPH as a headache entity.[12] In 1994, Siberstein et al., included NDPH in the group of chronic daily headaches along with chronic migraine (CM), chronic tension type headache (CTTH) and hemicrania continua, in their proposed revision to ICHD-1.[13] They considered NDPH to be similar to chronic tension type headache. However, they did not exclude patients with migrainous characteristics in their proposed criteria for NDPH. In 2004, ICHD-II was published that included NDPH in the group of “other primary headaches”.[1] In ICHD-II, the diagnosis of NDPH was offered to patients suffering from headache with characteristics similar to CTTH. This diagnostic criterion excluded patients with more than one migrainous feature. After 2004, a number of case series of patients with NDPH were published and many researchers proposed their own diagnostic criteria for NDPH with reasonable deviation from the ICHD II criteria for NDPH [Table 1]. The diagnostic criteria proposed by Peter J Goadsby included patients with “aggravation of pain with movement” and also allowed one migrainous feature, whereas Todd D. Rozen allowed the diagnosis of NDPH for patients with more than one migrainous characteristics.[14],[15] In 2013, ICHD 3rd edition beta simplified the diagnostic criteria for NDPH. This criterion emphasized only on the “clearly remembered onset” and continuation of headache on a daily basis from the onset for a minimum duration of 3 months. This criterion allowed the diagnosis of NDPH, irrespective of its location, character, and aggravation on movements, after exclusion of other primary or secondary headaches. Therefore, a patient fulfilling the criteria for NDPH and hemicranias continua will be offered the diagnosis of hemicrania continua. The ICHD III edition beta does not emphasize upon the need to remember the date of onset of headache. It states that the “clearly remembered onset of headache,” will be considered, which means that if the circumstances that led to headache are clearly remembered, this suffices for the diagnosis of NDPH.[2]
Table 1: Evolution of diagnostic criteria for NDPH

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 » Clinical Features Top

NDPH occurs abruptly, and continues from one moment to another, daily from its onset (or, on most days of the week), for a duration of 3 months or more. Usually, patients are able to recall the exact circumstances that were associated with the onset of NDPH. Twenty to eighty percent of the patients recall the exact date of onset of headache and nearly 80% patients remember the exact month of onset of headache [Table 2]. The prevalence of NDPH in the general population is between 0.03% and 0.1%.[7],[16] The proportion of NDPH among patients with chronic daily headache ranges from 2.24% to 11%.[17],[18] It may be as high as 36% among teenagers with chronic daily headache.[19] NDPH occurs in all age groups; however, most case series had patients with the mean age in the twenties to forties. Male and female subjects are nearly equally affected; however, the earlier reports had suggested a female preponderance for NDPH. The headache is usually bilateral, but less commonly, it is unilateral, unilateral and bilateral (on different days), and rarely side shifting. The character of headache can be throbbing, pressing, or stabbing, and a variable percentage of patients may have associated nausea, vomiting, and photo-phonophobia. Different triggers are also reported with NDPH [Table 2]. Nearly one-third of the patients may have a preceding headache but a history of increasing frequency of headache before it becomes continuous is against the diagnosis of NDPH. Depending upon the history of overuse of medications, NDPH can be classified as NDPH with or without medication overuse headache.
Table 2: Clinical characteristics of NDPH

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Differential diagnosis

NDPH is a well-defined headache syndrome. The diagnosis requires “clearly remembered” onset of headache but the headache itself can have a varied presentation.[20] The awareness of this headache is necessary to avoid unnecessary investigations, as majority of patients with NDPH have no known underlying cause. However, one should also be aware of secondary causes of NDPH that may be easily overlooked on routine computed tomographic (CT) or magnetic resonance imaging (MRI) scans of the brain. NDPH with no identifiable underlying cause is considered as primary NDPH, and that with an underlying cause are called secondary NDPH.

Secondary NDPH

[Table 3] summarizes the list of causes of secondary NDPH.
Table 3: Secondary causes of NDPH with their clinical and MRI features

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Subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is consistently listed as a cause of NDPH. Headache related to subarachnoid hemorrhage is acute and severe from the onset. Often, these patients are diagnosed early. Rarely, their initial CT scan is either normal or the radiological features of SAH on the CT scan are subtle and overlooked. When such patients persist with headache for more than 3 months, they then fulfill the criteria for NDPH. We encountered a couple of patients with SAH secondary to cortical venous sinus thrombosis where the diagnosis of NDPH was considered in view of chronic daily headache from the onset and a normal initial cranial CT scan. The diagnosis of SAH and cortical venous sinus thrombosis was made on the cranial CT venography [Figure 1].
Figure 1: A-35-year old lady presented with acute onset of holocranial headache for 4 months. Headache became daily from the onset but with intermittent exacerbations. Her clinical examination was normal. Her initial CT head was normal but a CT head with venography performed at 4 months of illness revealed (a) subarachnoid blood in right > left frontal lobe convexities with bilateral sulcal effacement, (b and c) empty-delta sign (black arrows) and (d) filling defect in the superior sagittal sinus due to sinus thrombosis was seen

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Headache secondary to cerebrospinal fluid (CSF) leaks

Low CSF pressure headache secondary to CSF leaks in not an uncommon headache in neurology wards. Often referred to as post-lumbar puncture headache, it can occur after an epidural anesthesia, spinal or cranial surgery, after head trauma and even after a Valsalva maneuver. The headache is characterized by a unique postural component where the headache appears within minutes of sitting or standing and improves promptly on lying down. Sometimes, the history of postural variability of headache is not available and the characteristic cranial MRI findings suggest the diagnosis. The uniform enhancement of cranial dura mater is the characteristic MRI finding [Figure 2]. The descent of cerebellar tonsils below the foramen magnum may also be seen. Additional investigations like a radionuclide scan, a gadolinium MRI with thin sections through the cribriform plate, or CT myelography/cisternography are sometimes required to diagnose the site of CSF leaks in patients without an identifiable cause.
Figure 2: A-55-year lady presented with headache for 6 months that was postural initially but later became continuous for 1 month. She had a history of undergoing a lumbar puncture to administer spinal anesthesia for a hysterectomy prior to the onset of headache. Her cranial MRI revealed uniform enhancement of the duramater. Her headache improved on conservative management for low CSF pressure headache

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Cortical venous sinus thrombosis

Patients with cortical venous sinus thrombosis (CVST) present with an acute, holocranial, throbbing headache that is worse in the morning and improves as the day progresses. It is more common in the post-partum state and in female subjects taking oral contraceptive pills. However, it is also seen in male patients, especially those suffering from any procoagulant state. The diagnosis is challenging when it present with only headache. However, the majority of patients eventually develop other features like visual obscurations, seizures, limb weakness or alteration of consciousness. Routine CT scan of the brain is usually normal or may rarely show “empty-delta” sign on post-contrast images. Cranial MRI may show venous infarcts, non-visualized venous sinuses or filling defects in the venous sinuses on post-gadolinium MR venography. Cortical vein thrombosis is not visualized on routine cranial MRI and post-gadolinium MR venography. Susceptibility weighted images (SWI) are very useful to detect cortical vein thrombosis. It shows areas of linear blooming on superficial brain sections [Figure 3].
Figure 3: A-24-year female patient presented with abrupt onset of headache that became daily and continuous for 4 months. Her neurological examination was normal. Her initial CT scan of the brain was normal. Her cranial MRI revealed a linear area of blooming in the high parietal region on SWI images suggestive of a cortical venous thrombosis that resulted in a small superficial parietal infarct. Her MR venography was normal

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Idiopathic intracranial hypertension (IIH)

Headache of IIH shares its features with headache secondary to CVST. Characteristically, it is seen in obese patients. Cranial MRI scans are usually normal or may show the empty sella sign, chinked lateral ventricles and tortuous optic nerves, flattening of the eye ball globe and peri-optic nerve sheath distension with CSF [Figure 4]. Fundus examination shows papilledema. Perimetry is more sensitive as it may show peripheral constriction of visual fields even before the appearance of papilledema. Untreated patients may progress to secondary optic atrophy and irreversible vision loss.
Figure 4: A-21-year female patient with morbid obesity presented with daily headaches for last 1 year. Her neurological examination was normal. Her fundus showed papilledema and perimetry revealed peripheral restriction of visual fields. Her CSF manometry revealed a pressure of 300 cm of water. Her cranial MRI revealed flattening of the eyeball due to protrusion of optic nerve head, tortuous optic nerves (a) and distension of the optic nerve sheath with CSF (b)

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 » Other Secondary Causes Top

Rarely, patients having a chronic subdural hematoma, an intracranial neoplasm or chronic meningitis may present with only headache. The headache characteristics of raised intracerebral pressure is present in all of these conditions. Presence of focal neurological signs, gait abnormality, urinary frequency/urgency, papilledema and meningeal signs may be a pointer to an underlying cause. Patients with chronic meningitis usually present with a triad of fever, headache and vomiting. However, the patients with fungal meningitis, like cryptococcal meningitis, may present with isolated headache. The MRI brain is also normal in a majority of patients and subtle findings like enlarged Virchow-Robin spaces may be only the abnormal finding [Figure 5].
Figure 5: A-25-year male patient presented with headache, occasional vomiting, photophobia and phonophobia for 4 months. His neurological examination was normal. His MRI brain was reported as normal but careful examination revealed prominent Virchow-Robin spaces in the basal ganglia (black arrows). His CSF examination revealed Cryptococcus on India Ink, positive enzyme linked immunosorbent assay for Cryptococcus, and the fungal culture was strongly positive for Cryptococcus Neoformans

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Primary NDPH

The diagnosis of NDPH requires the exclusion of other primary headaches [Table 4]. We have experienced that many patients with NDPH are treated as chronic tension type headache, as chronic migraine or as medication overuse headache for many years. This is because the diagnosis of these patients was made based on the characteristics of the headache and the history of onset of headache was not adequately asked. Hemicrania continua is another headache type that is sometimes confused with NDPH, especially in patients where the associated autonomic features are either very mild or not noticed by patients. It is, therefore, worthwhile to give an indomethacin trial in such patients with new-onset, unilateral, side-locked headache because unlike NDPH, the response to treatment in hemicrania continua is quite satisfactory. Other daily headaches like cluster headache, paroxysmal hemicrania and Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT) are characterised by overwhelming autonomic features, brief pain attacks, a circadian rhythm (in cluster headache) and therefore, these headaches are difficult to confuse with NDPH.
Table 4: Primary headache mimics of NDPH and clinical points to differentiate them from NDPH

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Pathophysiology of NDPH

The pathophysiology of NDPH is not known. It appears that the etiology of NDPH is multifactorial, and possibly therefore, it comprises of a myriad of headache types. Many patients correlate the onset of their headache with a preceding event referred to as 'the trigger'. Most commonly, an upper respiratory tract infection with Epstein Barr virus has been suggested as a possible trigger for NDPH but a conclusive proof of its cause-to-effect relationship with NDPH is lacking.[21],[22] Other triggers like stressful life events, cervical joint hypermobility, head trauma, other infections like diarrhea, familial disharmony, etc., have also been suggested.[7],[23],[24],[25] However, the importance of an event preceding the onset of NDPH is not known. We found triggers in nearly all of our patients with NDPH. Many agreed that they had a trigger when we offered a list of triggers to chose from. This shows that the triggers would have been missed if not suggested to the patients.[7] At the same time, this creates a doubt regarding the importance of triggers, as these patients are probably also prone to suggestions.

This opens up a debate on another question: whether or not there are specific personalities who are more prone to suffer from NDPH? We found a high proportion of patients with NDPH suffering from anxiety, depression, somatization and pain catastrophization at the time of their diagnosis.[7] Anxiety and depression have been shown previously in many patients with NDPH.[5],[6],[10],[26],[27] However, whether these psychiatric comorbidities play a background role and somehow cause NDPH or they are the result of existence of the long-standing treatment-refractory daily headaches is not known. A study of lifetime prevalence of psychiatric problems in these patients may resolve this issue.


[Figure 6] shows a flow-chart that may aid in the diagnosis of NDPH. Patients with a history of daily headache for more than 3 months qualify to be included in the category of chronic daily headache. Patients with unilateral side-locked headaches and with overt or subtle autonomic features require a trial of indomethacin. The diagnosis of hemicrania continua is confirmed by determining a good response to indomethacin. Those patients who are not responding to indomethacin may be considered for establishing the diagnosis of NDPH. Patients who clearly remember the onset of their headache may also be considered for the diagnosis of NDPH. Patients with clinical pointers towards the presence of secondary headache [Table 3] require further investigations for confirming the presence of secondary NDPH. Some additional MRI sequences like MR venography with gadolinium, susceptibility weighted images (SWI), MR angiography, and axial and coronal sections through the cavernous sinus and orbits are sometimes required for establishing the diagnosis of secondary NDPH. Patients with a crescendo frequency of migraine-like or tension-type headache, further leading to daily headache, are classified as having chronic migraine and chronic tension type of headache, respectively.
Figure 6: Flow diagram showing the scheme for the diagnosis of new daily persistent headache

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 » Treatment and Prognosis Top

There is lack of evidence regarding the effectiveness of any pharmacological, surgical or non-pharmacological treatment that may be called 'universally effective' in patients with NDPH.[28],[29] There are anecdotal reports of effectiveness of tricyclic anti-depressants, anti-epileptic drugs (gabapentin, topiramate, valproic acid), mexiletine, tetracycline, doxycycline, ketamine, intravenous methylprednisolone, botulinum toxin and nerve blocks (greater occipital, lesser occipital, auriculotemporal), and osteopathic manipulative treatment in patients with NDPH.[30],[31],[32],[33],[34],[35],[36],[37],[38],[39] Various treatment options for a refractory form of NDPH are summarized in [Table 5]. The discontinuation of medications in NDPH patients with medication overuse has not been as helpful, as seen in patients with migraine and medication overuse. The incidence of spontaneous remissions of NADH for years has been variably reported, ranging from 15% to 86%, in patients with NDPH.[5],[11],[40] Often, NDPH remains treatment-refractory and persists for years in a majority of patients.
Table 5: Treatment of refractory NDPH

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 » Summary Top

New daily persistent headache is an evolving entity. It is a constellation of several headache types grouped together owing to their peculiar abrupt onset. Therefore, experts consider NDPH as a syndrome. Despite several anecdotal reports of successful treatment with a number of pharmacological agents and nerve blocks, the NDPH largely remains treatment refractory. We believe that due to lack of awareness, NDPH is under diagnosed. Many patients with NDPH are treated sometimes for several years as chronic migraine or chronic tension type headache. There are not enough drug trials to determine an effective treatment agent/treatment protocol for these patients. We also believe that further research to determine the cause/effect relationship of the psychiatric conditions with NDPH, and adequate trials by pharmacological and psychological means to tackle these psychiatric co-morbidities of NDPH can be of some help to these patients.[43]

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Conflicts of interest

There are no conflicts of interest.

 » References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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