New Daily Persistent Headache (NDPH): another enigmatic and frequently post-infectious illness?

Making a thread for this because there are very few post-viral/post-infectious conditions where the pathophysiology remains enigmatic and because there are intriguing parallels with ME/CFS.

In headache-specialist neurology clinics the diagnosis of NDPH (new daily persistent headache) is increasingly being made. It refers to an unusual daily headache of quite sudden onset - often so sudden that the patient can identify the date on which it began - and is often unremitting from onset. It appears to have some interesting parallels to ME, including strong female predominance and, most notably, an onset often associated with an infection or flu-like illness. There are several case reports of an EBV-associated onset and at least one paper making a link to HSV and CMV (although, skimming the papers, some of these links appear rather tenuously made out); some mention unusual fatigue in NDPH patient cohorts.

The current diagnostic criteria are the ICHD-3 (International Classification of Headache Disorders, 3rd edition) (link). Previous criteria include the ICHD-2 definition, which was criticised for its narrowness and for including too many features of migraine, and the even older Silberstein-Lipton criteria. Prevalence estimates range from 0.03% to 0.1% in the general population; there are also suggestions that the paediatric prevalence may be higher. I would also suspect that many cases of NDPH will be treated as chronic migraine by GPs and many neurologists alike. NDPH is often refractory to treatment with the agents usually prescribed for migraine and tension-type headache.

A (probably incomplete) selection of papers that mention post-viral or post-infectious onset NDPH:

Swidan & Rosen (2006) Elevation of CSF tumor necrosis factor Alpha levels in NDPH and treatment refractory chronic daily migraine. Headache. 2006;46:897. Link. The authors assessed TNFα in CSF (n=20, elevated in 19). Notable quote: The thought is that NDPH patients in some manner have persistent glial activation after a viral illness or stressful life event with persistent cytokine production triggering a chronic inflammatory response. Many of the study patients had had their triggering infection 5–10 years prior to the CSF study but were still showing elevated CSF TNF alpha levels. As serum TNF alpha levels were not elevated in most NDPH patients, NDPH was not a disorder derived from systemic inflammation, but rather inflammation solely involving the CNS.

Mack (link) reported that, of 40 patients diagnosed with NDPH, 17 (43%) had an infectious onset, with half having +ve EBV serology at onset. He concluded that ... the onset of new daily persistent headache in childhood is typically associated with a physiologic stress such as an infection, head trauma, or post-surgery.

Rozen TD (2014) New daily persistent headache: an update. Curr Pain Headache Rep 18(7):431. (Link). Suggests that NDPH is a disorder of abnormal glial activation with persistent central nervous system inflammation and it may be a syndrome that occurs in individuals who have a history of cervical hypermobility.

Diaz-Mitoma et al. reported way back in 1987 (link) that in a case-control study 27/32 (84%) of patients compared to 8/32 (25%) of controls had evidence of "active" EBV infection, suggested that EBV reactivation contributed to NDPH pathogenesis & linked NDPH to "chronic mononucleosis", a term previously used in the US to describe apparent ME/CFS cases.

Li et al. (link) identified 56 patients who fulfilled the (older, narrower) Silberstein-Lipton criteria for NDPH, of which 40 were women and 16 were men; 30% had a reported infection-associated onset.

Meineri et al. (link) report a small case series of 18 patients diagnosed with NDPH, including some with a reported post-viral onset (flu-like illness).

Yamani et al. (link). A systematic review.

Santoni et al. (link) - an old paper describing a series of apparently infection-associated NDPH cases.

Rozen (2016) Triggering events and new daily persistent headache: age and gender differences and insights on pathogenesis-a clinic-based study. Headache 56(1):164–173. Link. Case series of 97 NDPH patients in a specialist headache clinic; precipitating events noted in 47% of the cohort, "flu-like illness" & "infection" in 22%.

Finally, in one of the few textbooks dedicated to headache disorders (Chronic Daily Headache for Clinicians), Rozen writes of NDPH: Given that a number of NDPH patients state that they had a cold or flu-like illness when their headache began, an infectious etiology for NDPH can be hypothesized. Some authors have linked Epstein-Barr virus (EBV) infection with NDPH. . . How an infection can induce NDPH is unknown. One may hypothesize an activated immune response to a new or reactivated viral infection leading to an autoimmune triggered headache, possibly by setting up a state of continuous neurogenic inflammation. . .

The quality of the evidence above is obviously very mixed, patchy and often highly speculative - but the fact that presumptively post-viral (& other post-infectious) cases have been reported decade after decade continues to pique my interest.

 

I've skimmed through the links but didn't find a detailed description of the headaches. I would be interested to know if they mostly resemble migraines, cluster headaches, tension headaches or anything else listed here. https://headacheaustralia.org.au/types-of-headaches/. If they have a common cause I imagine they would be similar in nature.

To answer my own question: https://headacheaustralia.org.au/headachetypes/new-daily-persistent-headache/ It's rather vague.

 

I had daily headaches for decades. I don't know when they started. As I got older I also developed frequent short-lived migraines with visual disturbances, like looking through a black and white kaleidoscope.

Luckily for me the headaches and migraines weren't severe. They just never went away. Then, as an accidental finding when a hospital doctor was checking for something else...

I was diagnosed with Normal Pressure Hydrocephalus (NPH), and after some investigation I was told I was probably born with it or developed it in infancy.

There was a treatment for the NPH - but doctors weren't convinced I actually needed to be treated, and it took seven years from discovery until I finally got operated on.

I could either have an ETV (Endoscopic Third Ventriculostomy) or get a shunt. For various historical medical reasons a shunt would most likely have been a disaster for me so I opted for the ETV.

And my daily headaches went away. My balance dramatically improved as well. I used to stagger and trip a lot, and bounce into walls particularly when I went round corners, as if I was drunk, but now I'm closer to normal in that respect too. My balance had been poor for as long as I could remember.

I was told by the neurosurgeon that my headaches were not related to the NPH because pressure in my head was "normal", but I think he was wrong and the pressure in my head was perhaps a bit higher than my head/brain was comfortable with. I got a lot of benefit from the ETV and I just keep my fingers crossed that it never closes up.

I still have very, very occasional migraines since the ETV, very like they were before the surgery but far fewer of them, and they are still mild and short-lived.

 

I always have a headache of some kind, varying from fairly mild background ones to murderous. A doctor who asked me to describe them said they were migraine type, but I didn't have auras then . When I first had an aura I saw a GP, but he didn't seem interested. My auras are rare, either orange vortices or iridiscent zigzag lines. Sometimes my entire vision becomes red, fuchsia or orange. I don't know if that's related. No one has offered me anything for them.