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Chapter 42
Headache Attributed toPreeclampsia orEclampsia
AndressaReginaGalego andElianaMeireMelhado

42.1 Introduction

This chapter aims to provide a comprehensive exploration of rare headache disor­ders through practical diagnostic approaches and case-based learning, offering valu­able insights for clinicians and researchers.
It is well known that headaches are a condition commonly associated with preg­nancy, often as an isolated and benign symptom [1]. However, headaches can also be a sign of more severe pathologies, such as preeclampsia and eclampsia, which are signicant complications with substantial morbidity and mortality [1]. Preeclampsia and related hypertensive disorders of pregnancy affect up to 10% of pregnancies. Neurological complications seen in association with preeclampsia include seizures (eclampsia), arterial ischemic stroke, reversible cerebral vasocon­striction syndrome (RCVS), posterior reversible encephalopathy syndrome (PRES), cervical artery dissection, cerebral venous sinus thrombosis, subarachnoid hemor­rhage (SAH), and intracerebral hemorrhage (ICH) [1]. Of these, ICH is the most devastating, directly causing up to 70% of deaths from preeclampsia [1].
Preeclampsia, which typically occurs after the 20th week of gestation, is charac­terized by high blood pressure and the presence of proteinuria, potentially leading to serious and signicant complications for both the mother and the baby [2, 3]. Eclampsia, on the other hand, results from the progression of preeclampsia, culmi­nating in the presence of seizures, which can lead to maternal and fetal death [2, 3]. Risk factors for the neurovascular complications of preeclampsia include older age, non-white race, heart disease, chronic hypertension, infections, prothrombotic and
A. R. Galego Department of Neurology, Base Hospital, São José do Rio Preto, São Paulo, Brazil
E. M. Melhado ( Department of Neurology, UNIFIPA (Padre Albino University Center), Catanduva, São Paulo, Brazil
Switzerland AG 2026 D. Uludüz et al. (eds.), Rare Causes of Headache Disorders, Headache,
https://doi.org/10.1007/978-3-032-10242-3_42
*)
395© The Author(s), under exclusive license to Springer Nature
396
A. R. Galego and E. M. Melhado
hypercoagulable states, and a history of migraine [2, 3]. Migraine is associated with an increased risk of both hypertensive disorders of pregnancy and maternal stroke [2, 3].
When discussing headaches attributed to preeclampsia and eclampsia, it refers to one of the neurological symptoms that can result from both increased blood pres­sure and endothelial dysfunction [4]. This specic type of headache can vary signi­cantly in presentation, duration, and characteristics [4]. Therefore, the presence of headaches during pregnancy should be a warning sign, especially when accompa­nied by other clinical and laboratory signs and symptoms [4].
Hypertensive disorders during pregnancy are reported to affect approximately 10–20% of pregnancies in the United States [5].

42.2 Pathophysiology

Preeclampsia is a progressive multisystem disorder characterized by the develop­ment of hypertension and proteinuria or organ failure after 20weeks of gestation, during pregnancy, labor, or postpartum [6]. It is believed that a combination of maternal and fetal/placental factors is the cause [6]. Abnormalities in placental vas­culature can lead to relative hypoxia, ischemia, or placental hyperperfusion, result­ing in the release of antiangiogenic factors into the maternal circulation, altering the mother’s systemic endothelial function and causing hypertension and other mani­festations of the disease (hematological, neurological, cardiac, pulmonary, renal, and hepatic) [6].
Preeclampsia can be broadly categorized into two subtypes: early-onset pre­eclampsia (or placental) and late-onset preeclampsia (or maternal) [7]. Both appear to have distinct etiologies and phenotypes. In terms of early-onset type, the defec­tive placenta is attributed to the development of preeclampsia [7]. Examination of the placenta in preeclampsia reveals numerous placental infarcts and arterial sclero­sis [7]. This is accompanied by placental hypoperfusion due to altered trophoblastic invasion and, therefore, placental ischemia [7]. Maternal preeclampsia arises due to the interplay between a healthy placenta and maternal factors that ultimately lead to microvascular damage [7]. This may be due to maternal endothelial dysfunction [7]. Since maternal preeclampsia occurs later in the gestational period, it can be man­aged expectantly until 37weeks of gestation [7]. Maternal preeclampsia occurs during the later stages of pregnancy, causing little or no change in arterial conver­sion, thus maintaining placental perfusion [7].
The underlying mechanism of the association between eclampsia and epilepsy is unclear [6]. However, hypertensive disorders during pregnancy, particularly eclamp­sia, are associated with impaired cerebral autoregulation, blood–brain barrier dis­ruption, and neuroinammation, which are possible underlying causes for the formation of cerebral edema [6]. Furthermore, preeclampsia and eclampsia can result in irreversible subclinical cerebral infarcts found in areas of cerebral edema [6]. These ndings are signicant and may be linked to the association with an increased risk of epilepsy in women with preeclampsia and eclampsia [6]. In other
42 Headache Attributed toPreeclampsia orEclampsia
conditions associated with acute brain injury, such as sepsis, a similar association with late epilepsy has been found [6].
397

42.3 Case Presentation

Patient: MCG, Female, 25years old
Gestational History: Pregnancies in 2018 and 2023
42.4 Clinical History andProgression
First Pregnancy (2018)
• 08-23-2018—Consultation (28weeks gestation)
• History of migraine with aura since childhood, with signicant worsening from
the fourth month of gestation.
• Episodes of right hemicrania, sometimes on the left.
• Aura accompanied by numbness in hands and feet, and blurred vision, lasting up
to 6 hours.
• During the week of consultation: migraine attacks with aura for three consecu-
tive days, associated with nausea, vomiting, photophobia, and phonophobia.
• One episode with temporary hemiplegia and speech difculty.
• Improvement only with hospital medication (Decadron, Dramin, Tramal,
glucose).
• Diagnosis: Migraine with aura aggravated in the second half of pregnancy with-
out hypertensive disorder.
• Management: Pyridoxine hydrochloride 250mg, coenzyme Q10 150mg for pre-
vention and acute treatment: Dipyrone drops + dimenhydrinate for pain.
• 09-24-2018—Consultation (37weeks gestation)
– Reduced frequency of attacks (3 events in the past month: 2 with aura, 1 with-
out aura).
– Preventive formula maintained, physiotherapy recommended.
• 10-25-2018—Consultation
– No attacks in recent weeks. – Complaints of tension headache for 1 week. – Foot edema and stretching difculties. – Advised to discontinue preventive vitamins.
• 11-22-2018—Telephone contact (postpartum)
– Cesarean delivery on 08/11/2018. – Postpartum headache, with prolonged aura. – Medication: Dipyrone, ibuprofen 400mg, ondansetron 4mg.
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A. R. Galego and E. M. Melhado
Second Pregnancy (2023–2024)
• 06-06-2023—Consultation (age 25)
• No preventive medication since 2018.
• Used copper intrauterine device (IUD) in 2019, removed for new pregnancy
attempt.
• Increase in attack frequency last month (1x/week, some severe).
• Attacks without aura: occipital pain with persistent discomfort.
• Attacks with aura: blurred vision, pre-crisis hand paresthesia lasting 30minutes.
• Prescription: Nortriptyline 0 mg/night, Sumax Pro + Meclin 25 mg for pain,
dipyrone 1g for mild pain.
• Signicant improvement observed.
• 01-11-2024—Consultation (15weeks gestation)
– Pregnant at 15weeks using vitamins. – Return of symptoms: prolonged visual aura (>1 hour), right-sided
paresthesia. – Episode of migraine with aphasic aura. – Medications used: Ibuprofen 600mg, dipyrone, tramadol. – Emotional complaint: Pain impacting conjugal relationship. – Conducted anesthetic blocks without corticosteroids.
• 01-24-2024—Consultation (17weeks gestation)
– Improvement after block on 11/01, 10 pain-free days. – Current diagnosis: Migraine with aura, worsening during pregnancy. – Management: Monitoring, anesthetic blocks as needed, guidance on hydra-
tion and proper nutrition. – Conducted additional blocks in 03/24 and 05/24.
• 06-30-2024—38weeks—Normal delivery
– In the week prior to delivery, experienced foot edema, persistent nuchal head-
ache without aura, and was hypertensive in obstetric consultation
170/110mmHg. – Obstetrician prescribed methyldopa, scheduled cesarean for 07/01, but went
into labor on 06/30 with a normal delivery. – Postpartum, experienced persistent nuchal headache, high blood pressure,
lower limb edema, and proteinuria; diagnosed with late gestational and imme-
diate postpartum preeclampsia, treated with methyldopa and candesartan. – Despite signicant nuchal pain, migraine was controlled with serial blocks. – Improvement and recovery observed within a month, followed by cardiologic
monitoring to verify the need for continued antihypertensive therapy. After
90days (October 2024), antihypertensives were discontinued, patient began
physical activity amidst maternal obligations, breastfeeding, and baby care.
42 Headache Attributed toPreeclampsia orEclampsia
399

42.5 Case Discussion

The patient has a history of migraine with and without aura, with signicant wors­ening during the second half of the rst pregnancy and the rst half of the second pregnancy. She experienced attacks with focal neurological phenomena, including transient hemiplegia and aphasia. Preventive treatment was not maintained consis­tently after the rst delivery, leading to an increased frequency of attacks.
In the second pregnancy, late-onset preeclampsia was observed, requiring inter­vention. The patient requires neurological monitoring and tailored interventions. She remains under observation for the frequency of migraine attacks.

42.6 Clinical Presentation

Patients with preeclampsia often present with complaints of new-onset headaches not explained by any other diagnosis (i.e., a history of headaches or migraines) that do not respond to medication [8]. This complaint may or may not be accompanied by additional reports of visual disturbances [8]. Patients may also experience epi­gastric pain associated with nausea or vomiting [8]. Shortness of breath and a per­ceived increase in swelling, both worsening compared to baseline pregnancy-related symptoms, may also be reported [8].
In patients with preeclampsia, the most prevalent indicators in history typically include the onset of a recent headache resistant to analgesics [8]. Preeclampsia can be asymptomatic or cause edema or excessive sudden weight gain (>5 lbs per week) [9]. Non-dependent edema, such as facial and hand edema (rings may no longer t on ngers), is more specic than dependent edema [8].
Eclampsia manifests as generalized (tonic–clonic) seizures [8].
Preeclampsia with severe features can cause organ damage; these characteristics may include severe headache, visual disturbances, confusion, hyperreexia, pain in the epigastric or right hypochondrium region (reecting hepatic ischemia or capsu­lar distension), nausea and/or vomiting, dyspnea [reecting pulmonary edema, acute respiratory distress syndrome (ARDS), or cardiac dysfunction secondary to increased afterload], oliguria (reecting decreased plasma volume or acute isch­emic tubular necrosis), and, rarely, stroke [8].
Patients presenting with any unique feature or a combination of these complaints should undergo a thorough physical examination [8]. This begins with an assess­ment of vital signs, specically blood pressure [8]. Patients with systolic blood pres­sure (SBP) 140mmHg or diastolic blood pressure (DBP) 90mmHg should raise suspicion for preeclampsia [8]. In patients 20weeks gestation or more, blood pres­sure readings on two occasions at least 4 hours apart should warrant further diag­nostic investigation [8].
The recent reevaluation of diagnostic blood pressure readings has expanded to include sustained hypertensive readings after repeated measurements to allow timely
400
A. R. Galego and E. M. Melhado
intervention with antihypertensive therapy [8]. These blood pressure readings include SBP 160 mmHg or DBP 110 mmHg. According to the American College of Obstetricians and Gynecologists (ACOG), patients previously diagnosed with gesta­tional hypertension presenting with these severe blood pressures should be diagnosed with preeclampsia with severe features, regardless of other diagnostic criteria [8].
When patients present with dyspnea, auscultation and percussion of the lungs should be performed to examine pulmonary disturbances [8]. An assessment of edema should also be completed, specically evaluating areas of dependent edema (gravity-related), such as the lower extremities, or independent edema, such as in the face or hands [8].
While preeclampsia often presents with a notable history and physical signs and symptoms, there are several atypical presentations [8].

42.7 Diagnostic Algorithm [9]

The diagnostic criteria for headaches attributed to preeclampsia or eclampsia are outlined in the “International Classication of Headache Disorders” (ICHD) under the following classication:
10. Headache Attributed to Disorder of Homoeostasis
10.3.4 Headache Attributed to Preeclampsia or Eclampsia [9]
Description:
Headache, typically bilateral and pulsating, occurring in women during preg­nancy or the immediate puerperium (up to 4 weeks postpartum) with preeclampsia or eclampsia. It resolves following the resolution of preeclampsia or eclampsia [9].
Diagnostic Criteria:
A. Headache in a woman who is pregnant or in the puerperium, fullling crite-
rion C [9]. B. Preeclampsia or eclampsia has been diagnosed [9]. C. Evidence of causation demonstrated by at least two of the following:
Headache developed in temporal relation to the onset of the preeclampsia or
eclampsia [9].
1. Either or both of the following:
(a) Headache has signicantly worsened in parallel with worsening of the
preeclampsia or eclampsia [9].
(b) Headache has signicantly improved or resolved in parallel with
improvement in or resolution of the preeclampsia or eclampsia [9].
2. Headache has at least two of the following three characteristics:
(a) Bilateral location [9]. (b) Pulsating quality [9]
42 Headache Attributed toPreeclampsia orEclampsia
401
(c) Aggravated by physical activity [9].
D. Not better accounted for by another ICHD-3 diagnosis [9].
Comments:
Preeclampsia and eclampsia appear to involve a strong maternal inammatory response, with broad systemic immunological activity [9]. A placenta seems essen­tial for their development, although case reports indicate that eclampsia can occur in the puerperium as well as during pregnancy. Preeclampsia and eclampsia are multisystem disorders with various forms [9]. Their diagnosis requires hypertension (>140/90mmHg) documented on two blood pressure readings at least 4 hours apart, or a rise in diastolic pressure of 15mmHg or systolic pressure of 30mmHg, coupled with urinary protein excretion >0.3 g/24 hours [9]. Additionally, tissue edema, thrombocytopenia, and abnormalities in liver function can occur [9].

42.8 Preeclampsia

Preeclampsia is diagnosed with the new onset after 20weeks of gestation of hyper­tension [blood pressure plus unexplained new-onset proteinuria (>300mg/24hours or urine protein/creatinine ratio0.3) and/or signs of target organ damage] [10]. Proteinuria is dened as >300mg/24hours [10]. The absence of proteinuria in less precise tests (e.g., urine dipstick tests, urinalysis) does not rule out preeclamp­sia [10].
In the absence of proteinuria, preeclampsia can be diagnosed if pregnant women meet diagnostic criteria for new-onset hypertension and exhibit signs of new-onset target organ damage [10].
Signs or symptoms of target organ damage may include one or more of the fol­lowing [10]:
• Thrombocytopenia (platelets <100×10^9/L)
Impaired liver function (aminotransferase >2 times normal) not explained by alternative diagnoses [10].
Severe and persistent right upper quadrant pain or epigastric pain unresponsive to medications [10].
Renal insufciency (serum creatinine >1.1mg/dL or doubling of serum creati­nine in the absence of kidney disease) [10].
Pulmonary edema [10].
New-onset headache unresponsive to medication and unexplained by alternative diagnoses [10].
Visual disturbances [10].
Other Diagnostic Categories of Preeclampsia Include
(H = hemolysis; EL = evated liver enzymes; LP =low platelet count) (HELLP) Syndrome: Classied as a severe form of preeclampsia and diagnosed when all of the following are present [11]: lactate dehydrogenase (LDH) ≥ 600 IU/L;
402
aminotransferases >2 times normal; and platelets <100×10^9/L.HELLP syndrome may have atypical clinical presentations, with the absence of hypertension or pro­teinuria in up to 15% of patients [11].
Preeclampsia Superimposed on Chronic Hypertension Diagnosed when a patient known to have chronic hypertension develops one of the following after 20weeks [12]: new unexplained proteinuria or worsening proteinuria; elevation of blood pressure above baseline; or signs of target organ damage. Women with chronic hypertension are at high risk of preeclampsia and should be closely monitored. An elevated uric acid level suggests a diagnosis of superimposed preeclampsia, rather than just chronic hypertension [12].
Patients with any type of preeclampsia are at risk of developing eclampsia [8]. Sometimes, eclampsia occurs before the diagnosis of preeclampsia [8].
A. R. Galego and E. M. Melhado

42.9 Eclampsia

Eclampsia is dened as new-onset tonic–clonic, focal, or multifocal seizures with­out other known causes (e.g., epilepsy, cerebral ischemia or arterial infarction, intra­cranial hemorrhage, or drug use) [8].

42.10 Fetal Assessment

The fetus is evaluated using non-stress tests or biophysical proles (including the assessment of amniotic uid volume) and tests that estimate fetal weight [8].
The link between migraine and adverse pregnancy outcomes, especially hyper­tensive disorders such as gestational hypertension and preeclampsia, may involve factors like inammation, endothelial dysfunction, and platelet activation [13]. Individuals with migraine often exhibit cardiovascular risk factors, such as obesity and chronic hypertension, increasing obstetric risks [13]. These adverse outcomes and migraine are associated with elevated risks of heart disease and ischemic stroke, suggesting a common etiology [13 pregnancy migraine was associated with 17% higher risks of preterm birth, 28% of gestational hypertension, and 40% of preeclampsia [13]. Migraine with aura was more associated with preeclampsia than without aura, while risks of hypertension and preterm birth were similar regardless of migraine type [13]. Pre-pregnancy migraine history is a signicant clinical marker of obstetric risk for vascular com­plications in pregnancies, independent of other established risk factors [13].
Researchers investigated the relationship between gestational hypertension, pre­eclampsia, and eclampsia with neurological disorders following childbirth [6]. Utilizing data from the National Patient Registry, the study included 648,385 women with no prior history of chronic hypertension or neurological disorders [6].
]. In a study with 30,555 pregnancies, pre-
42 Headache Attributed toPreeclampsia orEclampsia
403
The ndings revealed an increased risk of migraine, headache, epilepsy, sleep dis­orders, and mental fatigue among women with hypertensive complications during pregnancy [6]. Compared to normotensive pregnancies, the risk of developing such conditions was 27% higher for gestational hypertension, 32% for preeclampsia, and 70% for eclampsia [6]. The most pronounced association was between eclampsia and epilepsy, with a vefold increased risk. Women with preeclampsia and preterm delivery showed a higher risk of migraine and headache than those with term deliv­ery [6]. The researchers emphasize the need for postpartum follow-up for these women to identify neurological symptoms early [6]. Given the impact on quality of life, medical attention is crucial [6]. Future studies are necessary to understand the mechanisms involved and develop preventive strategies [6]. These ndings justify additional investigations and underscore the importance of continuous monitoring of these women for post-gestational hypertension neurological complications [6].

42.11 Treatment

The treatment of preeclampsia begins with early diagnosis and intervention, focus­ing on adequate blood pressure control and seizure prevention [8]. The denitive treatment for preeclampsia is delivery [8]. However, the risk of premature delivery is weighed against gestational age, fetal growth restriction, fetal distress, and the severity of preeclampsia. Immediate delivery after maternal stabilization (e.g., sei­zure control, initiation of blood pressure management) is indicated for [8]:
• Gestation of 37weeks
• Severe preeclampsia if gestation is 34weeks [8]
• Deterioration of renal, pulmonary, cardiac, or hepatic functions (including
HELLP syndrome) [8]
• Concerning results from fetal monitoring or testing [8]
• Eclampsia [8]
Patients with eclampsia or severe preeclampsia are typically admitted to a spe­cial maternal care unit or intensive care unit (ICU) [8]. Pregnant women between 34 and <37weeks of gestation who do not require immediate delivery are hospitalized for assessment, at least initially [8]. If the maternal and fetal state is reassuring, outpatient treatment is possible, which includes modied activity, blood pressure measurements, laboratory monitoring, non-stress fetal tests, and medical consulta­tions at least once per week [8]. If no criteria for severe preeclampsia develop, delivery can occur (e.g., by induction) at 37weeks [8]. In pregnancy with <34weeks, if delivery can be safely delayed, corticosteroids are administered for 48hours to accelerate fetal lung maturity [8]. Corticosteroids may be given to some stable patients after 34weeks and before 36 weeks of gestation if they have not been administered earlier [8].
404
A. R. Galego and E. M. Melhado

42.12 Antihypertensive Management [8]

Blood pressure control includes immediate antihypertensive management in cases of severe hypertension (160mmHg systolic and/or 110mmHg diastolic), along with maintenance antihypertensive management in the antepartum or postpartum period, depending on the specic diagnosis of preeclampsia [8]. Antihypertensive effective medications without adverse effects on the fetus include [8]:
• Beta-blockers, such as labetalol
• Calcium channel blockers, such as nifedipine
• Alpha-2 agonists, such as clonidine
• Vasodilators, such as hydralazine [8]
Commonly used medications for treating severe hypertension include intrave­nous (IV) labetalol, IV hydralazine, or immediate-release oral nifedipine [8]. Although no evidence suggests a benet of any IV medication as an initial choice for antihypertensive management, the choice is often dictated by the presence of IV access at the time of diagnosis, with oral nifedipine favored when IV access is unavailable [8]. Commonly used medications for maintaining blood pressure include oral labetalol, extended-release nifedipine, and extended-release cloni­dine [8].
42.13 Treatment ofEclampsia
Seizures in eclampsia are a medical emergency and require immediate treatment to prevent maternal and fetal mortality [14]. The management approach should bal­ance immediate support measures, seizure control, prevention of recurrent seizures, ensuring safe and optimized delivery, and closely monitored postpartum care [14].
Eclampsia treatment Includes [14]:
• Initial Support Measures: Call for assistance, manage seizures, prevent injuries,
ensure airway and oxygenation, and monitor vital signs and conduct laboratory
studies [14].
• Magnesium Sulfate: Preferred over other anticonvulsant treatments for prevent-
ing eclampsia-related seizures [14]. Magnesium sulfate is administered primarily
to prevent further convulsive activities, not to stop the current seizure [14]. The
standard recommended loading dose is 6g IV over 15–20minutes, followed by
a maintenance dose of 2g/hour [14]. In patients without IV access, a loading
dose of 10g intramuscularly, followed by a maintenance dose of 5g intramuscu-
larly every 4 hours, can be used as an alternate regimen [14]. In patients with
contraindications to magnesium sulfate (e.g., myasthenia gravis, hypocalcemia,
renal insufciency, cardiac ischemia, atrioventricular block, or myocarditis),
alternative anticonvulsant therapies (e.g., phenytoin and diazepam) may be con-
sidered [14]. Levetiracetam may be preferable in patients with myasthenia gra-
vis, a condition that can be exacerbated by phenytoin [14].