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23 Post-endarterectomy Headache
223

23.4 Case Discussion

This case illustrates a typical situation of post-endarterectomy headache. Symptoms appeared within the rst week after the procedure, and their characteristics were cluster headache-like, according to the 3rd edition of the International Classication of Headache Disorders (ICHD-3) [9]. Complementary tests were performed to rule out complications such as cerebral hemorrhage or ischemia, arterial stenosis, or dis­section; all of which were normal. According to the phenotype, treatment was suc­cessful with oxygen and verapamil.
23.5 Headache Characteristics ofPost-endarterectomy
The ICHD-3 describes three post-endarterectomy headache phenotypes: tension­like, cluster-like, and severe headache [9].
The rst type was described in detail by Tehindrazanarivelo etal., and, in this sample, approximately 60% of patients developed a headache after surgery. Most individuals presented a headache that appeared in the rst 5days after surgery (mainly in the rst 2days), which could be a continuous episode or several episodes per day, lasting from a few minutes to several hours (5min to 12h), and its average duration was 3days. Other characteristics of the headache are mainly bilateral loca­tion (72%), frontal (55%), of mild to moderate intensity (78%), pressure or heavi­ness (77%), without associated symptoms and without requiring treatment (77%) [4].
Some authors [3, 6, 10] have reported cases of cluster-like headache after endar­terectomy. Still, it was De Marinis etal. [5] who showed the particularities of the second type of headache, which occurred in 30% of individuals. The headache began, on average, 48h after the procedure, with each attack lasting 2–3 h, and occurring once or twice a day, during all the days it was active, which was generally about 2weeks. Only two cases that lasted 3–4months were described. The pain had a continuous-pulsating or pulsating characteristic of moderate-to-severe intensity, in the frontal, retroocular, periocular, and temporoparietal regions, always ipsilat­eral to the surgery. It may or may not be associated with local autonomic manifesta­tions (conjunctival hyperemia, lacrimation, nasal congestion, and rhinorrhea—25%) and Horner’s syndrome (25%) [5].
The third form of headache presentation is part of cerebral hyperperfusion syn­drome, which is a well-known complication that affects 1–3% of patients after end­arterectomy. It’s a condition characterized by numerous symptoms and ndings that include headache, seizures, hypertension, focal neurological decits, and intracere­bral hemorrhage [7, 11]. Headache is usually one of the rst symptoms of the syn­drome and begins 3days after surgery, abruptly or not, it can be unilateral (ipsilateral to the procedure) or bilateral, pulsatile, of severe intensity, associated or not with nausea, occurring in episodes over weeks to months [1214].
224

23.6 Diagnostic Algorithm

Step 1: Clinical Suspicion
Identify Key Symptoms:
– Headache initiating after carotid endarterectomy
Step 2: Clinical and Neurological Examination
Identify complications signs:
– Arterial hypertension – Focal neurological decits
Step 3: Diagnostic Workup
Brain Computed Tomography Scan:
– Assess for intracranial hemorrhage
Brain Magnetic Resonance Imaging:
– Look for signs of ischemic infarct
Carotid artery duplex:
– Assess for restenosis or dissection.
P. S. FaroSantos
Transcranial Doppler:
– Assess cerebral hemodynamic disturbances
Step 4: Apply ICHD-3 Diagnostic Criteria
A. Any new headache fullling criterion C B. Carotid endarterectomy has been performed C. Evidence of causation demonstrated by at least two of the following:
1. A headache develops within 1week of the carotid endarterectomy
2. The headache resolves within 1month after the carotid endarterectomy
3. Both of the following:
(a) The headache is unilateral, on the side of the carotid endarterectomy (b) A headache has one of the following three distinct characteristics:
• Diffuse mild pain
• Cluster headache-like pain occurring once or twice a day in attacks lasting 2–3h
• Pulsating severe pain
D. Not better accounted for by another ICHD-3 diagnosis.
23 Post-endarterectomy Headache
225

23.7 Management

Headache management should be based on its subtype, as each type probably has a different underlying pathophysiological mechanism. Another way to establish treat­ment is according to the headache phenotype.
A headache that begins early and has tension-like characteristics can be treated with analgesics and anti-inammatories alone, since it is usually mild and self­limiting. For the control of cluster-like headache, some authors have described a good therapeutic response to conventional drugs (oxygen, verapamil, and lithium) for the management of primary cluster headache [6, 10]. In addition, there is a report of a good therapeutic response to sumatriptan in a patient with cluster head­ache secondary to carotid artery dissection [15].
Meanwhile, treatment of the third headache subtype is mainly preventive, since cerebral hyperperfusion syndrome, the underlying cause of this headache, is a potentially serious complication [7]. Lee et al. [11] observed that patients who developed post-endarterectomy headache had greater intraoperative variability in blood pressure and suggested strict control of intraoperative blood pressure param­eters and limiting their variability to decrease the incidence of not only headache but also cerebral hyperperfusion syndrome. Furthermore, Dolan and Mushlin [12] described a case in which there was a dramatic improvement in post- endarterectomy headache and arterial hypertension after the use of prazosin, which inhibits postsyn­aptic α1-adrenoceptors.

23.8 Conclusion

Headache secondary to carotid endarterectomy is common but underestimated. It is essential to recognize its existence and understand its presentation so that proper investigation and treatment can be carried out, since it varies according to its pheno­type. Furthermore, it can precede serious complications, in the case of cerebral hyperperfusion syndrome, and its recognition can help in the management of this condition.

References

1. Abbott AL.Extra-cranial carotid artery stenosis: an objective analysis of the available evi­dence. Front Neurol. 2022;13:739999. https://doi.org/10.3389/fneur.2022.739999.
2. Leung YYR, Bera K, Urriza Rodriguez D, Dardik A, Mas JL, Simonte G, Rerkasem K, Howard DPJ. Safety of carotid endarterectomy for symptomatic stenosis by age: meta­analysis with individual patient data. Stroke. 2023;54(2):457–67. https://doi.org/10.1161/
StrokeAHA.122.040819.
226
3. Messert B, Black JA.Cluster headache, hemicrania, and other head pains: morbidity of carotid endarterectomy. Stroke. 1978;9(6):559–62. https://doi.org/10.1161/01.str.9.6.559.
4. Tehindrazanarivelo AD, Lutz G, PetitJean C, Bousser MG.Headache following carotid endarterectomy: a prospective study. Cephalalgia. 1992;12(6):380–2. https://doi.
org/10.1111/j.1468- 2982.1992.00380.x.
5. De Marinis M, Zaccaria A, Faraglia V, Fiorani P, Maira G, Agnoli A.Post-endarterectomy headache and the role of the oculosympathetic system. J Neurol Neurosurg Psychiatry. 1991;54(4):314–7. https://doi.org/10.1136/jnnp.54.4.314.
6. Björne A, Hindfelt B, Havelius U.Recurrence of cluster headache after carotid thromben­darterectomy. Headache. 1994;34(4):230–3.
hed3404230.x.
7. Lin Y-H, Liu H-M. Update on cerebral hyperperfusion syndrome. J NeuroIntervent Surg. 2020;12:788–93.
8. Ashina M, Hansen JM, Do TP, Melo-Carrillo A, Burstein R, Moskowitz MA.Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol. 2019;18(8):795–804. https://
doi.org/10.1016/S1474- 4422(19)30185- 1.
9. Headache Classication Committee of the International Headache Society (IHS). The International Classication of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.
https://doi.org/10.1177/0333102417738202.
10. Dirkx THT, Koehler PJ.Post-operative cluster headache following carotid endarterectomy. Eur Neurol. 2017;77(3–4):175–9. https://doi.org/10.1159/000456004.
11. Lee D, Batista PM, McMackin KK, Ha A, Trani J, Carpenter JP, Lombardi JV.Intraoperative blood pressure lability carries a higher risk of headache after carotid endarterectomy. J Vasc Surg. 2022;75(2):592–598.e1. https://doi.org/10.1016/j.jvs.2021.08.070.
12. Dolan JG, Mushlin AI.Hypertension, vascular headaches, and seizures after carotid endarter­ectomy. Case report and therapeutic considerations. Arch Intern Med. 1984;144(7):1489–91.
13. Pearce J.Headache after carotid endarterectomy. Br Med J. 1976;2:85–6. PMID: 1276821. PMCID: PMC1687795. https://doi.org/10.1136/bmj.2.6027.85.
14. Leviton A, Caplan L, Salzman E.Severe headache after carotid endarterectomy. Headache. 1975;15(3):207–10.
15. Leira EC, Cruz-Flores S, Leacock RO, Abdulrauf SI.Sumatriptan can alleviate headaches due to carotid artery dissection. Headache. 2001;41(6):590–1.
0.2001.041006590.x.
https://doi.org/10.1136/neurintsurg- 2019- 015621.
https://doi.org/10.1111/j.1526- 4610.1975.hed1503207.x.
https://doi.org/10.1111/j.1526- 4610.1994.
https://doi.org/10.1046/j.1526- 461
P. S. FaroSantos
Chapter 24
Headache Attributed toCerebral Venous Thrombosis (CVT)
DeryaUluduz andAynurÖzge

24.1 Introduction

Cerebral venous thrombosis (CVT) is a complex and potentially life-threatening condition characterized by the formation of a blood clot in the dural venous sinuses or cerebral veins, leading to increased intracranial pressure (ICP) and potential venous infarction [13]. This results in signicant morbidity and mortality if not promptly diagnosed and treated. CVT can affect both the supercial and deep venous systems of the brain, leading to a variety of clinical manifestations, includ­ing venous infarction and cerebral edema. CVT is relatively rare compared to arte­rial strokes, with an estimated annual incidence of about 3–4 per million people. However, it can be more common in specic populations such as young women and those with prothrombotic conditions.
Headache is a primary symptom of CVT, occurring in up to 90% of cases, and can sometimes present as the sole symptom, complicating its diagnosis [14]. The headache associated with CVT can be diverse, ranging from subacute onset to thun­derclap headache patterns, often with diffuse or bilateral characteristics [5, 6]. This variability, combined with the absence of specic diagnostic markers, makes early detection crucial yet challenging. The lack of a typical headache pattern and the potential for isolated headache presentation without other neurological signs further complicate the diagnosis, leading to delays in treatment initiation [4, 5]. The epide­miology of CVT-related headaches underscores their diagnostic challenge, with headache being the sole presentation in approximately 15% of patients [4, 7].
D. Uluduz (*) Medical Faculty, Neurology Department, Istanbul University Cerrahpasa, Samatya, Türkiye
A. Özge Mersin State Hospital, Mersin, 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_24
227© The Author(s), under exclusive license to Springer Nature
228
D. Uluduz and A. Özge
Understanding the relationship between CVT and headache is essential for improv­ing diagnostic accuracy and patient outcomes.

24.2 Case Presentation

A 24-year-old primigravida female presented to the emergency department with a generalized tonic–clonic seizure 2weeks postpartum following an uneventful vagi­nal delivery. The seizure lasted approximately 3min, and she remained unconscious for 20min afterwards. In the preceding 3days, she had been experiencing an excru­ciating headache that began insidiously but progressively worsened. The pain was predominantly occipital, radiating down to her neck and extending towards the ver­tex. She described it as a relentless, throbbing sensation, akin to an intense pressure building inside her skull. The headache was resistant to simple analgesics and was exacerbated by movement, particularly when she changed positions or attempted to stand. She also reported a sense of heaviness in her head, making it difcult for her to concentrate or engage in routine activities. Throughout this period, she developed associated symptoms of nausea and vomiting, which became more pronounced as the headache intensied. Bright lights and loud noises aggravated her discomfort, forcing her to retreat into a dark and quiet room. Despite her worsening symptoms, she attributed them to postpartum fatigue and dehydration, delaying medical atten­tion until the convulsive episode occurred.
Upon arrival, the patient appeared drowsy, with uctuating consciousness. Her vital signs were stable, with a temperature of 36.6°C, a heart rate of 70bpm, blood pressure of 110/60mmHg, a respiratory rate of 22 breaths per minute, and an oxy­gen saturation of 99% on room air. A general physical examination revealed no abnormalities. Neurological evaluation and fundoscopic examination were unre­markable. Her medical and family history, including thromboembolic conditions, were unremarkable, and she had no history of drug use or hormonal therapy. Given her young age and lack of signicant past medical history, neuroimaging was per­formed to rule out vascular pathologies.
A non-contrast computed tomography (CT) scan revealed hyperdensity in the superior sagittal sinus, suggestive of a dense clot sign, with no evidence of paren­chymal hemorrhage (Picture 24.1). Magnetic resonance imaging (MRI) with T2-FLAIR (uid-attenuated inversion recovery) sequences demonstrated hyperin­tense signals in the cortical and deep venous structures, indicative of venous con­gestion, without signs of infarction or hemorrhagic transformation (Picture 24.2). MR venography (MRV) conrmed the absence of ow voids in the superior sagittal sinus and transverse sinus, indicative of venous occlusion, without any arteriove­nous malformation or aneurysmal dilation (Picture 24.3). Laboratory investigations, including a complete blood count, biochemical screening, coagulation prole, inammatory markers, and a thrombophilia panel, yielded normal results. Specic tests for autoimmune and inherited thrombophilic conditions, such as
24 Headache Attributed toCerebral Venous Thrombosis (CVT)
Picture 24.1 Cranial CT demonstrates hyperdensity within the superior sagittal sinus, consistent with the dense sinus sign
229
Picture 24.2 Axial T2-FLAIR images; hyperintensity along the internal cerebral veins and vein of Galen, consistent with impaired venous drainage
antiphospholipid antibodies, Factor V Leiden mutation, protein C/S deciency, and lupus anticoagulant, were negative.
The diagnosis of postpartum cerebral venous sinus thrombosis (CVT) was estab­lished, and anticoagulation therapy with heparin was initiated, later transitioning to therapeutic oral warfarin. On the fourth day of hospitalization, she experienced
230
Picture 24.3 MR venography; reduced or absent ow in the right transverse and sigmoid sinuses, and interrupted ow in the superior sagittal sinus
D. Uluduz and A. Özge
another generalized tonic–clonic seizure lasting 2min, prompting the initiation of levetiracetam at a dose of 1000mg per day. She was discharged with full neurologi­cal recovery and was advised to continue oral anticoagulation therapy.

24.3 Case Discussion

Cerebral venous sinus thrombosis is a rare but serious postpartum complication, often presenting with seizures, headaches, and focal neurological decits. Pregnancy and the puerperium increase the risk due to hypercoagulability and endothelial changes. The diagnosis relies on a high degree of clinical suspicion and conrma­tory imaging, with MR venography being the gold standard for detecting venous occlusions. In this case, the patient presented with postpartum headache, seizure, and focal neurological decits, necessitating urgent neuroimaging. The CT scan revealed a dense clot sign, while MRI and MR venography conrmed sinus throm­bosis. The absence of identiable thrombophilic risk factors suggested that puerpe­rium was the primary contributing factor.
Early anticoagulation is the cornerstone of treatment, preventing thrombus prop­agation and promoting recanalization. Seizures are common in CVT patients, requiring antiepileptic therapy in cases of recurrent episodes. The patient’s favor­able outcome highlights the importance of early recognition and timely interven­tion. This case underscores the need for heightened awareness of CVT in postpartum patients presenting with new-onset headaches, seizures, or neurological decits.
24 Headache Attributed toCerebral Venous Thrombosis (CVT)
231
Prompt diagnosis and appropriate management are crucial in preventing complica­tions and ensuring a good prognosis.

24.4 Pathophysiology

The primary mechanisms underlying cerebral venous thrombosis (CVT)-related headaches involve venous outow obstruction, increased intracranial pressure (ICP), cortical vein infarction, cerebral edema, and venous hemorrhage. Each of these mechanisms contributes to the complex headache prole associated with CVT, making diagnosis and management challenging (Fig.24.1).
Venous Outow Obstruction and Increased Intracranial Pressure (ICP) When a venous sinus or cerebral vein becomes occluded, normal venous drainage is dis­rupted, leading to venous congestion. This congestion results in a secondary increase in ICP due to impaired cerebrospinal uid (CSF) absorption at the arachnoid granu­lations. The pressure buildup within the cranial vault can exert direct mechanical stress on pain-sensitive structures, including the dura mater and meningeal vessels, which are richly innervated by nociceptive bers originating from the trigeminovas­cular system. The elevated ICP manifests clinically as a headache that is often
Fig. 24.1 Venous obstruction triggers inammation, blood–brain barrier disruption, increased intracranial pressure, and nociceptive activation, ultimately leading to cortical infarction, edema, and headache
232
D. Uluduz and A. Özge
described as severe, progressive, and diffuse. It is frequently exacerbated by Valsalva maneuvers, such as coughing, straining, or positional changes, due to transient increases in venous pressure that further compromise cerebral venous drainage [810]. Additionally, elevated ICP can lead to papilledema, which may contribute to visual disturbances and worsen the headache through secondary optic nerve involve­ment [11].
Cortical Vein Infarction and Neuroinammation In addition to venous conges­tion, CVT can lead to cortical vein infarction, a consequence of sustained venous hypertension and hypoxia [4, 8]. The resultant ischemic injury triggers an inam­matory cascade involving microglial activation, cytokine release (e.g., interleukin-1β (IL-1β), tumor necrosis factor alpha [TNF-α]), and increased permeability of the blood–brain barrier (BBB) [12].
This inammatory response plays a pivotal role in sensitizing pain pathways. The activation of nociceptive bers within the dura and cortex leads to increased release of pain-producing mediators such as substance P, calcitonin gene-related peptide (CGRP), and bradykinin [13]. These molecules amplify pain transmission by lowering the activation threshold of trigeminovascular afferents, making the headache more persistent and refractory to conventional analgesics [14].
Cerebral Edema and Its Contribution to Headache Pathophysiology Cerebral
edema is another signicant contributor to CVT-related headaches and can be clas­sied into cytotoxic and vasogenic edema. Cytotoxic edema results from cellular energy failure due to ischemia, leading to intracellular water accumulation. In con­trast, vasogenic edema arises from BBB disruption, allowing plasma proteins and uids to enter the extracellular space [8, 9, 15]. Both forms of edema exacerbate ICP elevation and contribute to worsening headache symptoms. The expansion of brain tissue within the xed cranial vault intensies meningeal and vascular stretch, further activating pain-sensitive structures. This can lead to diffuse, non-localized headaches that mimic primary headache disorders such as migraines or tension-type headaches, complicating the differential diagnosis.
Venous Hemorrhage and Meningeal Irritation
Venous hemorrhage is a potential
consequence of severe venous hypertension leading to vessel rupture. The extrava­sation of blood into cerebral tissue can irritate the meninges, further exacerbating headache severity. Hemorrhagic transformation of venous infarcts adds another layer of complexity by increasing localized mass effect and potentiating secondary inammatory responses [15]. The presence of hemosiderin–laden macrophages and blood degradation products can induce oxidative stress, leading to prolonged activa­tion of nociceptive pathways. This results in a persistent, throbbing headache that may resemble a thunderclap headache or other secondary headache disorders such as subarachnoid hemorrhage.