What is a chronic daily headache?

When a person experiences headaches for at least 15 days a month and continues for 3 months or longer, these kinds of headaches are called chronic daily headaches.

What is a new daily persistent headache?

New daily persistent headache (NDPH) is a type of chronic daily headache that has not occurred before. Its onset is distinct, occurs suddenly, and the pain is continuous, becoming weaker within 24 hours. ¹ NDPH was discovered by Dr. Walter Vanast in 1986. He found that people who never had a headache developed daily chronic headaches after they had a viral infection. An example of this is the aftermath of the COVID-19 pandemic, where many people have experienced this type of headache.² Vanast found that these headaches can stop occurring by themselves (spontaneous remission)^.2

Studies have found that individuals with this type of condition do not respond to regular treatments. Moreover,  NDPH is not a symptom but a syndrome.³ 

Subtypes of new daily persistent headache

• Self-limiting subtype: Resolves on its own without any therapy¹
• Refractory subtype: Do not respond to any form of aggressive treatment¹

Features of persistent headache

Similarities of NDPH with

Differences

The difference is that the onset is sudden, distinct and clear; pain is chronic and doesn't go away with typical headache medications.¹

Triggers for NDPH

This poorly understood syndrome has multiple triggering factors, such as:⁴

• Post infections - Viral infections like COVID-19, bacterial toxins
• Physical injury
• Psychological trauma, stress, anxiety and depression
• After surgical procedures
• Hypermobility in the joints

Role of immunity in causing headaches

It has been hypothesised that disturbances in the immune system (built-in security system of the body) may lead to these headaches. ⁵ To understand this, let's first understand the immune system.

Types of immunity

1. Innate - present since birth, the body's  natural defence system
2. Acquired - immunity acquired in response to an antigen (foreign body like bacteria, virus, pollen and toxins), which involves B and T cells of the body

Association of the immune system with NDPH

Studies have shown that people with NDPH may be associated with ⁷

• Rise in inflammatory mediators and cytokines -TNF-A and IL-6 
• B and T cell imbalance 
• Autoimmune response
• Increased Central nervous system inflammation 
• Genetics

What is an autoimmune response?

When our immune system attacks our own body instead of defending it, it is described as an autoimmune response.⁵ Our body produces auto-antibodies and T cells, which destroy our natural defence cells.

Common autoimmune diseases associated with headaches

There are many autoimmune diseases which affect different parts of the body. Some of them associated with headache are⁶

• Joints and muscles - Sjögren's syndrome, Rheumatoid arthritis
• Skin and blood vessels -  Lupus, systemic vasculitis
• Brain and nervous system - Systemic Lupus Erythematosus, Multiple Sclerosis
• Digestive system - Celiac disease 

What causes headaches in autoimmune diseases?

• Neuroinflammation 

 Autoimmune disease mistakenly attacks the brain, nerves and spinal cord, causing inflammation, release of cytokines, altering pain pathways in the brain and leading to new daily persistent headaches. ^6,7  This is seen in conditions such as multiple sclerosis.

• Mitochondrial dysfunction

Microglia (glial cells) are present in the brain. They work as scavengers, controlling inflammation (neuroinflammation) and maintaining the normal functional balance of the brain. In certain autoimmune diseases or infections, this homeostatic balance is disturbed by damage or dysfunction of mitochondria(the powerhouse of the cell) inside microglia, leading to a cascade of events, including damage to the brain and causing new daily persistent headaches. ⁸

• Autoantibodies

In certain autoimmune conditions like acute encephalitis, there are antibodies produced by the body that attack nerve receptors and glial cells in the brain, affecting the nerve signalling, leading to NDPH.⁶ 

• Dysregulation of Cortisol and HPA Axis

The hypothalamic–pituitary–adrenal (HPA) axis and the autonomic nervous system (ANS) play vital roles in regulating stress. ⁹ Activation of the HPA axis for a long time can lead to an increase in cortisol levels, triggering neuroinflammation and increased sensitivity to pain (central sensitisation). Chronic activation of the autonomic (sympathetic ) nervous system further leads to an increase in muscle tension and tone around the head and neck, all of which cause headaches.⁹

Pathophysiology linking autoimmune disease and headaches

Autoimmune diseases are multifactorial with environmental or genetic causes. Similarly, headaches can be caused in various ways, with multiple factors involved.

• Studies have shown a common gene involvement associated with immunological disorders and primary headaches, such as migraine
• Genes encoding for HLA antigens change into multiple forms and play a role in causing autoimmune diseases, as well as migraine⁶
• Increased inflammatory cytokines act as a risk factor for autoimmune diseases and new daily persistent headaches⁷
• Reduction in natural killer cells and CD8 cells, and an increase in CD4 cells, is seen in autoimmune diseases and primary headaches⁶

Diagnosis

• Detailed history of headache and differences from other headaches
• Autoimmune diseases: systemic symptoms like weight loss, fatigue, joint pain or rash along with headache¹⁰
• Neurological signs and symptoms: numbness, cognitive changes, speech and vision problems and seizures
• Laboratory tests for autoimmune diseases:¹¹
  • Autoantibodies - ANA test
  • Analysis of cerebrospinal fluid in the brain for markers
  • Thyroid antibody test
• Neuroimaging: MRI for signs of vasculitis, changes in the brain and nervous system

Treatment options

Most of the aggressive treatments for headache have either failed or provided only partial relief from NDPH. ¹

Acute treatment 

Studies have shown Triptans to improve pain severity in people with NDPH. ¹²Studies on Muscle relaxants, Tricyclic antidepressants,  Selective serotonin reuptake inhibitors and Antiepileptic drugs showed 30% people responding to the treatment.¹² Drugs like Amitriptyline, Gabapentin, Methysergide, Propranolol and Sodium valproate have been used to treat NDPH but have responses varying between 10 and 30%.¹²

Conventional headache therapies like painkillers may not be completely effective and can lead to side effects from overuse.

Injectable and neuromodulatory treatments 

• Cranial nerve blocks¹²
• Injections of Sodium valproate¹²
• Botulinum toxin A¹²

Autoimmune disease treatment

Steroids are used to treat inflammatory autoimmune diseases, and biologics are used to treat diseases such as arthritis  and lupus.

SEEDs approach¹³

S – Sleep: proper sleep for 7-8 hours every day.

E – Eating: Certainfoods are risk factors for migraine and can irritate the nervous system, leading to headaches. These include: alcohol, caffeine, refined sugar, corn and tannins. Choosing a healthy and balanced diet while avoiding food triggers can reduce the occurrence of headaches.

E – Exercise: Moderate intensity exercise helps reduce persistent headaches. 

D – Dehydration: adequate hydration (1.5L per day) for better physical and mental health.

S – Stress: Stress acts as a trigger for NDPH, and practising mindfulness and meditation can control cortisol levels, released in response to stress

Emerging therapies

Treatments targeting the immune system are being trialled in animals and humans. CGRP antibodies show promise for curing NDPH.¹⁴

Challenges and future directions

1. Lack of well-controlled, large-scale studies on NDPH 
2. Low prevalence of NDPH
3. Difficulty in differentiating it from other headaches and disorders
4. Need for reliable immune biomarkers for identifying chronic headaches

Summary

New daily persistent headaches, being uncommon and poorly understood, can adversely affect a person's physical and mental health. Headaches are commonly seen in people with autoimmune diseases. They appear as a manifestation or complication of a systemic disease or a psychiatric disorder. More long-term research is required to find a cure for NDPH; until then, it remains an enigma.

FAQs

Are NDPH and migraine the same?

It has overlapping features with migraine, but is sudden, chronic and distinct.

What should I do if I have a persistent headache for 3 months?

Avoid over-the-counter medication and visit a healthcare professional.

Is NDPH an autoimmune disorder?

No, it may have an autoimmune origin, but multiple other factors can also trigger it

Can NDPH ever go away?

It may or may not resolve completely. It can take up to 3 years to resolve completely. There isn't enough data on it.