Pregnancy-associated intracranial hypertension syndrome – diagnostic and therapeutic management

Introduction

The data from the specialized literature, as well as the cases encountered so far, have demonstrated that the dynamics and complexity of the cerebral venous system surpass those of the cerebral arterial system, not only on an individual level but also between the two hemispheres of a single individual. Venous drainage of the brain remains ultimately incompletely elucidated. Therefore, the cerebral venous system is classified based on its relationship with the cortex, into the following parts: dural venous sinuses, representing the superficial circulation, and deep cerebral veins. The dural venous sinuses are the foundation for the proper regulation of normal venous drainage⁽¹⁾.
 

Increased intracranial pressure (ICP) is a syndrome caused by a variety of neurological and non-neurological diseases and, uncontrolled, it can lead to catastrophic deterioration and death. Understanding the pathology and physiology of the different appropriate management is possible. Most treatment modalities have evolved from treating traumatic brain injury (TBI) and are applied to treat increasing ICP of other etiology⁽²⁾.

Transverse sinus hypoplasia is the underdevelopment or incomplete development of these sinus areas that play a role in our cranial structure, affecting everything from drainage to intracranial pressure. A hypoplastic left transverse sinus indicates a smaller than normal sinus canal, which can impede drainage. The causes of this hypoplasia may be multiple, ranging from genetic predisposition to environmental factors encountered during fetal development⁽³⁾.

It is considered a multifactorial disease that can be triggered by a variety of genetic and environmental factors. In the ISCVT study, almost 44% of patients had more than one cause or predisposing factor. The proportion of unknown causes is about 15%, and there are still many unresolved⁽⁴⁾. Although this condition can present potential complications, such as increased risk of sinus thrombosis, it is not inherently dangerous for everyone. Each individual case varies, with some people having no symptoms at all. Early detection and monitoring can lead to a personalized approach that minimizes any health risk, ensuring that people with this condition can lead a healthy and active life. Intracranial hypertension is characterized by signs and symptoms of increased intracranial pressure, being associated with obesity, the patients being mostly women, usually of reproductive age. The most common symptoms include headaches, loss of vision, pulsatile tinnitus, and back and neck pain, but the clinical presentation is highly variable, which may lead to delayed diagnosis. The diagnosis is usually based on the modified and updated Dandy criteria: papillary edema, absence of identifiable secondary causes, and elevated ICP⁽⁵⁾.

Less rarely, pain is radicular, in the neck or back. Other nonspecific symptoms of meningeal irritation may be present, including nausea and vomiting and photophobia. Focal symptoms, seizures, signs of encephalopathy, or altered level of consciousness may also reflect a syndrome of intracranial hypertension in the context of meningitis, venous infarction, or cerebral venous thrombosis. When the onset of symptoms is acute, a secondary cause is suspected⁽⁶⁾.

Intracranial pressure monitoring is currently considered the gold standard in the management of patients with intracranial hypertension or severe brain injuries, serving as a key pillar in guiding therapeutic decisions. However, there is no definitive evidence to support this medical practice. The use of invasive devices that facilitate proper drainage of cerebrospinal fluid, such as external ventricular drains or intraparenchymal microtransducers, is considered the benchmark for patient care. Advanced imaging methods like CT, transcranial Doppler or MRI have not proven to be superior to invasive methods for monitoring intracranial pressure⁽⁷⁾.

Clinical case

We present the case of a 38-year-old woman with no significant history and no heredocolateral history, with an ongoing pregnancy of 27-28 weeks, who was admitted to the Department of Neurology of the University Emergency Hospital Bucharest, Romania, for suspected transverse sinus thrombosis and comitial seizures. It should be mentioned that the patient was at her second pregnancy, the first one about five years before, without any special events during pregnancy and delivery by caesarean section.

From personal documents and the patient’s statements, the symptoms had started about three months before the hospitalization, with altered general condition, severe headache, nausea, vomiting, episodes of loss of consciousness and weight loss. The symptoms persisted and, because the cephalalgic syndrome became the major symptomatology, with pain and cervical contracture and diffuse headache, a neurologic consultation was performed, followed by a native brain MRI which revealed an asymmetry of the lateral ventricles, with their increased size.

Objective neurologic examination: no focal neurologic signs, except for severe headache with nausea, dizziness, tinnitus and episodes of altered consciousness for which the diagnosis of LP (lumbar puncture) was refuted. The symptomatology continued and, because the LP (lumbar puncture) episodes became more frequent, cerebral MRI was requested, and the suspicion of right transverse sinus thrombosis versus hypoplasia was raised.

Further investigations were continued, primarily to rule out acute meningitis, autoimmune diseases, thrombopathies and neoplasms. An ophthalmological examination, including fundus exam and computed tomography, did not reveal papilledema. Weighing the risks and benefits of initiating delivery at a gestational age of 28 weeks, the decision was made to delay delivery, aiming to alleviate the maternal symptoms while simultaneously monitoring the fetal well-being. Corticoste­roids and antithrombotic therapy were administered, and repeated lumbar punctures for the cerebrospinal fluid (CSF) evacuation were performed, along with dynamic cytological analysis of the CSF. Under these conditions, the headache symptoms improved for 5-7 days. Throughout hospitalization, the pregnancy was closely evaluated by the obstetrics and gynecology team, with local clinical examinations, cardiotocographic monitoring and ongoing ultrasound assessments; from an obstetric standpoint, there were no significant changes.

At a gestational age of 32 weeks, the headache symptoms became therapeutically unmanageable, prompting a multidisciplinary team of neurologists, obstetricians and an intensive care physician to decide on a caesa­rean section for maternal benefit. Preoperatively, a lumbar catheter for CSF drainage was placed and kept in place for 24 hours. Under spinal anesthesia, a caesarean section was performed, delivering a live female infant weighing 1900 g, with an Apgar score of 6. The placenta, along with fetal annexes, was sent for histopathological examination. The newborn was admitted to the neonatal intensive care unit and showed favorable progress over time.

Approximately 24 hours postoperatively, the patient returned to the neurology department. Her recovery was favorable under anticoagulant, antibiotic and analgesic therapy, with both headache and general condition improving.

The gradual initiation of physiotherapy was planned, and a contrast-enhanced brain MRI revealed a reduction in lateral ventricle size, though it raised a possible suspicion of meningitis. Two weeks postoperatively, the patient’s neurological status deteriorated, with worsening general condition and consciousness, accompanied by nausea, vomiting, headache, tinnitus and cervical paravertebral muscle contracture, unresponsive to lumbar CSF drainage. An emergency brain MRI revealed ventriculomegaly (Figure 2).
 

A ventriculoperitoneal shunt placement was decided upon, in collaboration with the neurosurgery team.

After intervention, the patient showed a rapid favorable response, with repeating serological and CSF cytology tests remaining negative for infection or inflammation. The neurological symptoms were completely resolved, and the patient’s well-being significantly improved following the shunt placement. She was discharged one week postoperatively, with plans for periodic follow-up examinations.

Discussion

Etiology of increased intracranial pressure: cerebral or extracerebral expansive processes, generalized cerebral edema, increased venous pressure, obstruction of cerebrospinal fluid (CSF) flow, or any condition that increases the CSF volume. In the given case, all these possible causes were ruled out, including tumors, cerebral infarction, contusions, subdural or extradural hemorrhages, abscesses, acute liver failure, hypertensive encephalopathy, hypercapnia, and Reye’s hepatocerebral syndrome.

As for possible remaining etiologies, increased venous pressure remains under consideration, caused by cerebral venous sinus thrombosis, heart failure, or obstruction of the superior mediastinal veins, jugular veins, and obstruction of CSF flow and absorption. Such obstruction may occur at the level of the ventricles or the subarachnoid space at the brain’s base, which would also lead to hydrocephalus.

Another mechanism affecting the cerebrospinal fluid drainage is represented by the diffuse meningeal involvement due to various causes, such as infectious, carcinomatous, granulomatous, and hemorrhagic conditions. Additionally, any condition that increases CSF volume, such as meningitis, subarachnoid hemorrhage or choroid plexus disorders, was also considered.
 

During hospitalization, the patient exhibited low-grade fever and respiratory symptoms, prompting testing for SARS-CoV-2, which returned positive. Presepsin and IL-6 levels were monitored dynamically, and the patient tested negative approximately 14 days after the initial positive test. The current data indicate that the neurological symptoms were not negatively impacted by the concurrent viral infection.

The estimated prevalence of pregnancy among IIH (idiopathic intracranial hypertension) patients is between 2-12%, with IHH occurring in pregnancy at a similar rate to the general population, with pregnancy long considered a risk factor for the development and exacerbation of IBH (benign intracranial hypertension) due to hormonal changes and prenatal weight gain. In addition, the subsequent pregnancies are not a risk factor for the recurrence of HII. And coexisting IBH with pregnancy is not likely to worsen the visual outcomes.

The examination of a pregnant patient with symptoms suggestive of intracranial hypertension begins with an ophthalmologic examination to diagnose papillary edema, and, if confirmed, secondary causes should be treated before an etiology is identified.

Neuroimaging is necessary to exclude space-occupying lesions or cerebral venous sinus thrombosis, which should be considered especially in pregnant patients who are predisposed to hypercoagulability⁽⁹⁾.

Although a variety of therapeutic options are described in the literature, very few have proven effective in symptoms’ remission. Acetazolamide, a carbonic anhydrase inhibitor, may be teratogenic, being associated with limb abnormalities in rats and mice. According to the pregnancy risk classification administration in the United States, it falls into category C, but there are no adequate and well-controlled studies in pregnant women. In general, because safety in pregnancy cannot be established, their administration should be done with caution until the 20^th week of pregnancy⁽¹⁰⁾.

Corticosteroids have limited use in acute visual complications, being classified as a category B risk factor. Steroids have been found to cause lip and palate defects in animals. Lumbar puncture directly and immediately reduces intracranial pressure and relieves HII symptoms in pregnancy. Lumbar puncture is considered by some authors to be the treatment of choice during pregnancy, and most patients experience symptomatic improvement for several days after a lumbar puncture⁽¹¹⁾.

For patients presenting with fulminant symptoms or for those who do not tolerate or respond to medical treatment, several surgical options are available: cere­bro­spinal fluid drainage, optic nerve sheath fenestration (ONSF) and, more recently, venous sinus stenting (VSS)⁽⁴⁾.

Conclusions

Intracranial hypertension syndrome is a multifactorial condition that is challenging to manage therapeutically and, when associated with pregnancy, the entire diagnostic and therapeutic algorithm presents a difficulty for the clinician. In our case, the outcome has been favorable for both the patient and the newborn, at least for now. In the short and long term, we aim to closely monitor the patient to fully elucidate the etiology of the disease.

Disclosure: All authors have participated equally in developing this study.

Autori pentru corespondenţă: Elena-Evelina Stoica E-mail: evelina.almajanu@gmail.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

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