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34 Headache Attributed toChiari Malformation Type I(CM1)
329
Treatment must be adjusted for each case. For patients with mild-to-moderate
symptoms, conservative strategies might effectively control headaches, reduce neuroinammation, minimize central sensitization, and optimize CSF dynamics. For
severe cases with signicant functional impairment, surgical decompression
remains the best option. Nevertheless, decision-making should go beyond rigid protocols and consider the patient holistically (i.e., history, symptoms, and impact of
headaches on daily life).
With advances in the understanding of CM1 and its neurological implications,
emerging neuroimaging tools and biomarkers may enhance diagnostic accuracy and
optimize therapeutic strategies. The main challenge remains balancing scientic
evidence with a patient-centered approach. This chapter highlights the importance
of a multidisciplinary perspective that integrates technical expertise with personalized treatment to improve clinical outcomes for these patients.
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C. B. Tavares
Part VI
Headache Attributed to a Substance
or Its Withdrawal
Chapter 35
Headache Attributed toaSubstance or Its
Withdrawal: Carbon Monoxide (CO)Induced Headache
EsraAcimanDemirel
35.1 Introduction
Carbon monoxide (CO) is a gaseous signaling molecule that is endogenously produced in the human body by the enzyme heme oxygenase [1]. CO functions as a gas
carrier, playing a role in nociception, neurotransmission, and cerebral hemodynamics [2]. Additionally, CO has been identied as a pain-modulating neurotransmitter
[3]. Exposure to CO can result in various neurological effects. A well-documented
effect of CO exposure is the manifestation of headaches [4]. Typically, CO levels
between 10% and 20% have been shown to induce mild headaches devoid of accompanying gastrointestinal and neurological symptoms. Levels between 20% and 30%
have been associated with moderate-to-throbbing headaches and irritability. Levels
of 30–40% have been associated with severe headaches, nausea, vomiting, and
blurred vision. Levels exceeding 40% often result in a lack of reported headaches
due to altered consciousness [5]. Levels between 50% and 60% frequently lead to
myocardial ischemia, ventricular arrhythmias, pulmonary edema, lactic acidosis,
hypotension, coma, seizures, and death [6].
Carbon monoxide-induced headache is a type of headache that is caused by
exposure to carbon monoxide. This headache typically resolves on its own within
72hours after the exposure is eliminated from the body [5]. Headache is frequently
the initial and most prevalent symptom of CO poisoning, which can lead to neurological and systemic complications if left untreated.
E. A. Demirel (*)
Zonguldak Bulent Ecevit University, School of Medicine, Zonguldak, Turkey
Switzerland AG 2026
D. Uludüz et al. (eds.), Rare Causes of Headache Disorders, Headache,
https://doi.org/10.1007/978-3-032-10242-3_35
333© The Author(s), under exclusive license to Springer Nature
334
E. A. Demirel
35.2 Pathophysiology ofCarbon Monoxide-Induced
Headaches (Fig.35.1)
The pathophysiology of CO-induced headaches involves several mechanisms:
1. CO Binding to Hemoglobin
– CO binds to hemoglobin 200–250 times more strongly than oxygen, forming
carboxyhemoglobin (COHb) [7].
– This reduces the blood’s ability to carry and deliver oxygen to tissues, leading
to cellular hypoxia [3, 4].
2. Hypoxia in the Brain
– Decreased oxygen delivery results in cerebral hypoxia, leading to neuronal
stress and metabolic dysfunction.
– The occurrence and severity of CO-induced headache depend on both the
COHb level (the severity of hypoxia) and the amount of free CO reaching the
nervous system [3, 4].
Fig. 35.1 Mechanism of carbon monoxide-induced headaches
35 Headache Attributed to a Substance or Its Withdrawal: Carbon Monoxide…
3. Vasodilation and Increased Blood Flow
– Hypoxia caused by CO exposure leads to compensatory cerebral vasodila-
tion, increasing cerebral blood ow (CBF) in an attempt to deliver
more oxygen.
– This vasodilation, mediated by nitric oxide (NO) and other pathways,
increases intracranial pressure (ICP), leading to headaches [3, 4, 8].
4. Mitochondrial Dysfunction
– CO also binds to cytochrome c oxidase, an enzyme in the mitochondrial elec-
tron transport chain. CO inhibits cytochrome c oxidase.
– This disrupts ATP production, causing energy failure in neurons and leading
to headache and neurological symptoms and worsening headache symptoms.
– Hypoxia and the CO toxicity directly on mitochondria cause glutamate
release, which activates N-methyl-d-aspartate (NMDA) receptors, further
leading to neurologic injury [9].
5. Inammation
– CO exposure triggers oxidative stress, damaging brain cells and increasing
inammatory mediators.
– This can irritate pain-sensitive structures in the brain, contributing to head-
ache and neuroinammation [9].
335
6. Neurotransmitter Imbalance
– CO has been identied as a neurotransmitter that modulates pain [9].
– It is endogenously produced and affects pain transmission via cyclic guano-
sine monophosphate. It shows a strong afnity for the heme in soluble guanylate cyclase. This afnity activates soluble guanylate cyclase, leading to
increased production of cyclic guanosine monophosphate and glutamate
release [9].
– CO interacts with nitric oxide, which plays an important role in the mecha-
nisms underlying migraine formation [8]. This interaction causes dilation of
cerebral vessels and the formation of free radicals, leading to headaches [4, 8].
Figure visually summarizes the complex pathophysiology of carbon monoxideinduced headaches.
35.3 Case Presentation
A 46-year-old female patient presented to the emergency department due to smoke
inhalation. The incident occurred during the night while she was asleep, following
a re that broke out due to an explosion from a mobile phone battery. The patient
did not notice the re while sleeping and was awakened by her husband, who had
just returned home from work and saw the house lled with smoke. Upon waking,
336
she became aware that the entire house was engulfed in smoke. Emergency services
were called, and she was promptly brought to the hospital. Upon evaluation, the
patient complained of a persistent, throbbing headache accompanied by dizziness
and nausea. She denied any signicant past medical history and was a non-smoker.
Her vital signs on admission were blood pressure, 130/85mm Hg; heart rate 95
beats per minute; respiratory rate, 20 breaths per minute; and oxygen saturation,
97% on room air. Neurological examination revealed no abnormalities.
• Arterial blood gas (ABG) analysis revealed a carboxyhemoglobin (COHb) level
of 14% (normal <2% in non-smokers).
• Electrocardiogram (ECG) was normal.
• Chest X-ray showed no abnormalities.
• Complete blood count and metabolic panel were within normal limits.
• Brain magnetic resonance imaging (MRI) was normal.
She was immediately placed on 100% high-ow oxygen via a non-rebreather
mask, which helps expedite CO elimination. Symptomatic treatment for headache
and nausea was provided. She was admitted for follow-up in the hospital by anesthesia. After six hours of oxygen therapy, the patient’s symptoms improved signicantly, and his COHb levels decreased to 5%. Following the administration of
treatment, the patient’s headaches were alleviated, and they were fully resolved
within 24hours. The patient was discharged from the hospital. One week later, she
underwent a neurological evaluation at the outpatient neurology clinic. During this
evaluation, no headaches or additional neurological symptoms were observed.
E. A. Demirel
35.4 Case Discussion
This case highlights the importance of promptly recognizing and treating carbon
monoxide poisoning, even in the absence of severe symptoms. A high index of suspicion, the appropriate use of carboxyhemoglobin measurements, timely administration of oxygen therapy, and meticulous follow-up are imperative to ensure
optimal patient outcomes.
35.5 Headache Characteristics ofCO-Induced Headache
A carbon monoxide (CO)-induced headache typically presents with distinctive features that help in its recognition and differentiation from other headache types. It is
often described as a dull, continuous pain affecting both sides of the head, with
moderate-to-severe intensity. The headache tends to worsen with physical activity,
and it is commonly accompanied by nausea and vomiting [4, 8]. The frontal region
(forehead) is the most frequently reported site of pain, although it can be diffuse and
35 Headache Attributed to a Substance or Its Withdrawal: Carbon Monoxide…
involve multiple areas of the head [4, 10]. Studies show that 66% of patients report
frontal pain, while 41% describe the pain as throbbing.
Associated symptoms often include a range of neurological and systemic signs,
such as dizziness, weakness, confusion, blurred vision, and shortness of breath,
which may accompany or even precede the headache [4, 10]. The onset of symptoms usually occurs within 12hours of CO exposure, and resolution is expected
within 72hours after the exposure ends.
One of the key diagnostic clues is the rapid improvement of symptoms following
the administration of 100% oxygen, which helps distinguish CO-induced headaches
from other types. Interestingly, recent studies indicate that symptom severity correlates more strongly with the duration of CO exposure than with the level of carboxyhemoglobin (COHb) in the blood [4].
337
35.6 Third Edition ofInternational Classication
ofHeadache Disorders (ICHD-3) Diagnostic Criteria [5]
8.1.3 Carbon Monoxide (CO)-ınduced Headache
Diagnostic Criteria:
A. Bilateral headache fullling criterion C
B. Exposure to carbon monoxide (CO) has occurred
C. Evidence of causation demonstrated by all of the following:
1. Headache has developed within 12hours of exposure to CO
2. Headache intensity varies with the severity of CO intoxication
3. Headache has resolved within 72hours of elimination of CO
D. Not better accounted for by another ICHD-3 diagnosis.
Acute CO poisoning is diagnosed by anamnesis and clinical suspicion. There are no
standard criteria or laboratory tests for diagnosing acute CO poisoning. COHb levels measured in blood gas are partially related to the degree of intoxication. Oxygen
pressure measurements tend to be normal because PO2 reects O2 dissolved in the
blood and CO does not affect this measurement [6].
Carbon monoxide hemoglobin (COHb) levels are of critical importance in the
diagnosis of CO poisoning. Non-smokers typically exhibit levels of less than 2%,
while smokers generally display levels of 5–10%. Levels exceeding 10–15% suggest the presence of poisoning, and levels above 25% are considered severe and
potentially fatal. The severity of poisoning can be gauged by the COHb levels,
which in turn inform treatment methods. Carboxyhemoglobin levels above 25% are
considered potentially fatal and require treatment with hyperbaric oxygen treatment
[11, 12].
338
Lesions seen on neuroimaging are as varied as the spectrum of clinical signs and
symptoms observed after CO poisoning. There are no pathognomonic radiographic
changes seen on computed tomography. Magnetic resonance imaging (MRI) is a
sensitive imaging method that identies cerebral lesions in the acute period of CO
poisoning. It was determined that acute CO poisoning may lead to acute brain damage, and 40.6% would be detected in brain MRIs taken in patients during the acute
phase [10, 13].
E. A. Demirel
35.7 Treatment
35.7.1 Oxygen Therapy (100% Oxygen)
The primary therapeutic intervention for cases of CO poisoning is the administration of 100% oxygen. The administration of high-concentration oxygen has been
demonstrated to facilitate the rapid displacement of CO from hemoglobin, thereby
enabling the restoration of normal oxygen-carrying capacity in the blood. The
administration of oxygen is a primary treatment for CO poisoning. The rapid displacement of CO from the hemoglobin in the blood facilitates the restoration of
normal oxygen-carrying capacity. Oxygen therapy accelerates the elimination of
CO from the body, as CO is excreted through the lungs [11, 14].
In a study by Okan etal., it was demonstrated that the use of “oxygen only” was
as adequate as the combination of “oxygen plus metoclopramide” or “oxygen plus
metamizole sodium” in treating headaches induced by CO poisoning [14].
Carboxyhemoglobin levels above 25% are considered potentially fatal and
require treatment with hyperbaric oxygen treatment [11, 12].
35.8 Conclusion
Carbon monoxide-induced headache is a common and early symptom of CO poisoning that requires prompt recognition and intervention. The pathophysiology
involves multiple mechanisms, including hypoxia, cerebral vasodilation, mitochondrial dysfunction, oxidative stress, and neurotransmitter imbalances. Although
COHb levels are helpful for diagnosis, they do not always correlate with symptom
severity, making clinical judgment essential.
Oxygen therapy remains the primary and most effective treatment, facilitating
rapid CO elimination and symptom resolution. This case underscores the importance of timely diagnosis and management in preventing potential neurological
sequelae. Clinicians should maintain a high index of suspicion for CO poisoning in
patients presenting with unexplained headaches, particularly those with a relevant
exposure history. Increased awareness and education about CO toxicity are crucial
35 Headache Attributed to a Substance or Its Withdrawal: Carbon Monoxide…
339
for both healthcare professionals and the general public to ensure early detection
and prevention of CO-related morbidity and mortality.
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