A Rare Case of Secondary Pseudotumor Cerebri Syndrome in a Female with a Tongue Base Tumor: A Case Report

Abstract

Introduction

The pseudotumor cerebri syndrome (PTCS) is characterized by elevated intracranial pressure in the absence of intracranial structural lesions, with normal cerebrospinal fluid. PTCS may be primary, also known as idiopathic intracranial hypertension (IIH), or secondary to an identifiable cause such as obstructive sleep apnea (OSA). Primary and secondary PTCS share similar clinical features.

Case Presentation

We report the case of a 43-year-old female of normal weight initially suspected of IIH, who was subsequently diagnosed with secondary PTCS caused by a tongue base tumor, leading to OSA. She presented with symptoms consistent with PTCS, including headache, transient visual obscurations, and progressive visual decline. Fundoscopy revealed severe bilateral papilledema, and lumbar puncture showed an opening pressure of 43 cm H₂O. Despite treatment with acetazolamide, her vision worsened, and optic nerve sheath fenestration was performed. Further investigation identified OSA caused by a benign tumor of the tongue as the underlying etiology. Following continuous positive airway pressure therapy her headache and papilledema resolved.

Conclusion

The case illustrates the importance of thorough search for secondary causes in patients diagnosed with PTCS.

Introduction

Pseudotumor cerebri syndrome (PTCS), as an umbrella term, encompasses cases of primary (idiopathic) intracranial hypertension (IIH) and secondary IIH [1, 2]. The latter mimics IIH but has an identifiable underlying cause [2]. PTCS is characterized by elevated intracranial pressure (ICP) in the absence of a detectable structural cause such as a tumor or hydrocephalus or abnormal cerebrospinal fluid (CSF). Most cases of IIH affect women of reproductive age with obesity [1, 3]. This phenotype is also prevalent in secondary PTCS [4], emphasizing the need for meticulous consideration of rectifiable and potentially treatable causes in all patients and the need for multidisciplinary management.

Although obesity is a well-established risk factor, IIH may also occur in patients of normal body weight, suggesting a multifactorial etiology and thus a possible link to the secondary PTCS [3]. In such cases, contributing factors may be obstructive sleep apnea (OSA), medical, or hormonal influence [1]. Notably, OSA has increasingly been recognized as a possible contributor to elevated ICP [5]. Upper airway obstruction in OSA is often precipitated by obesity but may have other causes. Whether OSA is an obesity-related comorbidity in IIH, or an independent primary cause is controversial and may be either or in different individuals.

Clinically, IIH presents with symptoms of raised ICP, including headache, transient visual obscurations, pulsatile tinnitus, nausea, diplopia, and papilledema. If left untreated, the condition may lead to permanent loss of vision [6] due to secondary optic nerve atrophy. A diagnosis in patients without papilledema is allowed when strict neuroimaging criteria and opening pressure suggest raised ICP [2, 7].

First-line treatment involves weight loss (if relevant) and carbonic anhydrase inhibitors such as acetazolamide. In severe or refractory cases, surgical options including optic nerve sheath fenestration (ONSF), venous sinus stenting, or CSF diversion may be indicated [8]. The same approach applies to secondary PTCS when addressing the underlying condition proves insufficient. In this case report, we present a female of normal weight with secondary PTCS where several potentially contributing conditions and comorbidities were identified highlighting the importance of considering alternative risk factors, both in typical and atypical presentations.

Case Report

A 43-year-old female with a medical history of hypertension, hypothyroidism, and rosacea presented with intermittent visual obscurations in her right eye lasting a few seconds, occurring up to 10 times daily over the course of 1 year and with subjective decline in vision. The episodes were particularly provoked by postural changes and became notably more prominent and bilateral following an infection with coronavirus disease 3 weeks earlier, after which she experienced a permanent inferior visual field defect in her left eye. Four years earlier, she had suffered from recurrent pressing headaches related to cognitive stress but had otherwise no history of headache.

Although she was of normal weight with a body mass index of 24.6, she had gained 12 kg over the past 2 years attributed to hypothyroidism. However, she seemed to be well regulated with levothyroxine with normal thyroid-stimulating hormone at presentation. The neurological examination was normal apart from blurred vision and left relative afferent pupillary defect.

Computed tomographic venography ruled out cerebral venous thrombosis; however, the findings included a partially empty sella turcica and a slender left transverse venous sinus. A contrast-enhancing lesion at the base of the tongue was identified on the computed tomographic scan and suspected to be a cavernous hemangioma. Cerebral magnetic resonance imaging (MRI) further revealed posterior scleral flattening, optic nerve head protrusion, mild enlargement of Meckel’s cave, and optic nerve tortuosity. A lumbar puncture revealed an opening pressure of 43 cm H₂O. The CSF was normal, and the diagnosis of IIH was suspected. The patient was prescribed 500 mg acetazolamide three times daily, which was soon after increased to 1,000 mg three times daily.

Snellen best corrected visual acuity was 1.2 logMAR bilaterally with a left relative afferent pupillary defect. Automated perimetry revealed right upper and lower arcuate defects and a severe left concentric visual field constriction (perimetric mean deviation −6.7/−20.4 dB). Ophthalmoscopy confirmed the presence of true bilateral chronic papilledema Frisén grade 4 (with total obscuration of segments of the large vessels of the optic disc) superimposed on buried bilateral optic disc drusen (ODD), verified by ultrasound in the right eye and only visible in both eyes on Heidelberg enhanced depth imaging optic coherence tomography months later when the papilledema had subsided [9]. Peripapillary retinal nerve fiber layer (RNFL) thickness was bilaterally increased 335/298 µm with a predominantly left macular ganglion cell layer volume loss (0.98 and 0.82 mm³, respectively). Due to severe bilateral papilledema with signs of secondary left optic nerve atrophy, she underwent left ONSF by superomedial transconjunctival orbitotomy 14 days after the initial detection of papilledema (Fig. 1).

Fig. 1.

a, b Optic discs with chronic papilledema Frisen grade 4 three days after left optic nerve sheath fenestration (ONSF). c, d Optic discs with atrophy one and a half years later after remission of papilledema. Optic nerve scans by enhanced depth imaging optical coherence tomography (Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany) performed after resolution of papilledema revealing buried optic disc drusen (white arrows pointing at hyporeflective structures with a full or partial hyperreflective margin) in right (e) and left (f) eye. OCT, optic coherence tomography.

The procedure was technically challenging, as the optic nerve was difficult to expose and only a sparse flow of CSF was observed, but otherwise uneventful. However, metabolic acidosis was incidentally identified during arterial cannulation (pH 7.25, normal anion gap). The most likely reason was proximal renal tubular acidosis induced by acetazolamide in combination with nonsteroidal anti-inflammatory drugs. Both were discontinued, she was treated with bicarbonate and recovered fully.

In the meantime, due to the patient’s slightly atypical phenotype and the suboptimal response to acetazolamide, secondary causes were extensively searched for. A new MRI of the brain, neck, and spine showed new changes around the left optic nerve interpreted as ONSF sequelae, as these had not been present on the MRI 8 days earlier and the procedure had been technically difficult (Fig. 2). A new lumbar puncture performed in the left lateral outstretched decubitus and optimal position revealed an opening pressure of 36 cm H₂O. CSF analysis showed a mildly positive myelin oligodendrocyte glycoprotein antibody signal, but neither pleocytosis, oligoclonal bands, elevated neurofilament levels, nor abnormal cells on flow cytometry. The CSF was considered of normal composition.

Fig. 2.

Magnetic resonance imaging of cerebrum and orbits. Axial (a) and coronal (c) T2-weighted sequences of the orbit with fat saturation do not show optic nerve sheath distension. a, b Posterior globe flattening with papillary protrusion is seen bilaterally. c, d Presumed postoperative changes in the left orbit are seen with intraconal and retrobulbar stranding with contrast enhancement. e On the sagittal T2-weighted sequence of the brain sella turcica is partially empty. On the coronal T2-weighted images of the orbits (f), the tumor is seen at the base of the tongue.

Postoperatively, the papilledema gradually subsided in the left eye revealing progressive RNFL atrophy corresponding to the ganglion cell layer loss seen preoperatively. The papilledema in the right eye, on the other hand, remained almost unchanged. One month after surgery, a right papilledema Frisén grades 3–4 persisted compared to Frisén grade 2 with atrophic pallor in the left eye. Peripapillary RNFL measured 249/146 µm. Visual parameters were stable, but the patient complained of worsening of the visual obscurations in her right eye. With no clinical improvement following ONSF and side effects from acetazolamide, she was empirically given 75 mg prednisolone daily for 10 days.

Her medications, nutritional supplements, and personal care products were scrutinized. An extended blood workup, including autoimmune testing (e.g., myelin oligodendrocyte glycoprotein antibody, interleukin-2 receptor), a paraneoplastic panel, and testing for factor V Leiden mutation, yielded negative results.

Her vision remained at risk in both eyes, and because prednisolone had no apparent effect, acetazolamide was reintroduced at a low dose (250 mg three times daily) with close monitoring of renal function and blood carbon dioxide (CO₂) levels. This time, a therapeutic effect was observed with reduced visual obscurations and papilledema remission to Frisén grades 2–3 on the right and grade 1 on the left eye.

Concurrently, the patient was referred to a home sleep (WatchPAT) assessment for evaluation of OSA due to reported snoring, although sleep apnea had been ruled out years ago. Moderate position-dependent OSA with a total apnea-hypopnea index (AHI) of 18.7 events per hour was diagnosed and lead to the initiation of nightly continuous positive airway pressure (CPAP) therapy alongside a gradual increase in acetazolamide 500 mg three times daily. CPAP therapy completely resolved her headaches and markedly improved her general wellbeing. Acetazolamide was gradually tapered and ultimately discontinued, leaving CPAP as monotherapy reducing AHI to 6 events/h.

Owing to the lesion at the base of the tongue, she was also referred to the Department of Ear, Nose and Throat (ENT). A failed biopsy led to a follow-up MRI 3 months later and a 2 cm × 2 cm cone-shaped benign-looking tumor was diagnosed and deemed unsuitable for surgery.

At 6 months, a new WatchPAT assessment showed improvement of respirations with AHI 0 events/h. Papilledema had completely resolved, but optic atrophy, and stable, but extensive visual field defects, especially on the left eye (perimetric mean deviation –6.6/–17.7 dB), remained. Peripapillary RNFL was 84/50 µm. Due to intolerance issues with the CPAP mask, surgical removal of the tongue tumor was reconsidered. At ENT follow-up, a drug-induced sedation endoscopy revealed that the OSA was caused by the benign tumor at the base of the tongue – ultimately identifying the underlying trigger for this fulminant case of secondary PTCS that was initially interpreted as IIH. The patient was considered a potential candidate for a mandibular advancement device as an alternative to CPAP and was referred to a certified dentist for further evaluation. She remained well-treated on CPAP with good compliance.

Discussion

We present a rare cause of secondary PTCS in a 43-year-old female of normal weight with progressive visual disturbances and papilledema caused by a tongue base tumor, resulting in OSA. Despite typical clinical and radiological features consistent with IIH, her somewhat atypical phenotype with a BMI under 30 kg/m² and limited response to standard treatment prompted further investigation. Brain imaging revealed signs suggestive of IIH that was confirmed by lumbar puncture. These findings are not unique for primary PTCS (IIH) but are also seen in secondary PTCS and other conditions of raised ICP.

Atypical features of this patient were her relatively high age [10], as IIH usually presents in the second and third decade, and her normal BMI, but she did have a recent pronounced gain of weight as is often seen in IIH. As such, she was not overly atypical and could theoretically have had IIH. It accentuates the diagnostic complexity of IIH and particularly in patients who lack the classical risk factors.

A turning point in the diagnostic process was the identification of OSA that was linked to an unnoticed benign airway-obstructing mass. Pathophysiologically, OSA may contribute to elevate ICP through intermittent hypoxia and hypercapnia, leading to cerebral vasodilation, increased venous pressure, and impaired CSF absorption [11]. The marked clinical improvement of the patient after the initiation of the CPAP therapy supports this mechanism. A potential confounder could be a delayed effect of the ONSF; however, this is unlikely as the positive effect of ONSF is usually seen within hours to a few days, and the procedure had been performed nearly 50 days before CPAP initiation.

While OSA is recognized as a comorbidity in IIH, its function as a primary driver of IIH is likely underrecognized. The actual case emphasizes the importance of considering OSA in patients with atypical IIH presentations but also typical cases of IIH in which obesity-related OSA is prevalent [11]. Early diagnosis and relevant treatment are paramount to prevent permanent visual damage as seen in this patient.

Thyroid disease and the treatment hereof have also been reported to be causal in secondary PTCS [12] but were considered unrelated here; her disease was well managed for several years and there was no temporal relationship to levothyroxine therapy initiation.

ODD causing pseudopapilledema may confuse the interpretation of the fundus, but in this case, true papilledema was evident from the severe RNFL thickening covering the large vessel on the optic discs and dynamic RNFL changes with treatment. While premorbid, asymptomatic RNFL and ganglion cell layer loss caused by chronic compression from ODD cannot be definitively ruled out, it may have contributed to the observed optic atrophy.

Clinically, this case illustrates the value of multidisciplinary collaboration, involving neurologists, ophthalmologists, radiologists, otolaryngologists, sleep specialists, and nephrologist. A multidisciplinary approach to management is beneficial from both a patient and societal perspectives [13, 14]. The case also highlights the benefit of a systematic approach in PTCS management.

Conclusion

This case supports a broader understanding of pseudotumor cerebri as a multifactorial syndrome. Secondary PTCS caused by OSA should be considered as a differential diagnosis of IIH, particularly in patients of normal weight with atypical presentations or poor response to conventional therapy. Identifying and treating the underlying cause – in this case, a benign airway-obstructing tumor – may significantly alter the clinical trajectory and improve long-term outcomes. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000549878).

Statement of Ethics

The patient was informed of the purpose of the case presentation, and she gave her written informed consent to the publication of her case. Ethical approval is not required for this study in accordance with local or national guidelines.

Conflict of Interest Statement

Rigmor Højland Jensen has given lectures for AbbVie, Eli Lilly, Lundbeck, Merck, Novartis, Pfizer, and Teva; served as an investigator in clinical trials with Eli Lilly, Novo Nordisk, Novartis, and Lundbeck; is the director of the Danish Headache Center, Lifting The Global Burden of Headache and Founder of Master of Headache Disorders at University of Copenhagen; and has received research funding from Lundbeck Foundation, Rigshospitalet, The Medical Society in Copenhagen, Novo Nordisk Foundation, Tryg Foundation, and University of Copenhagen. The other authors have no conflicts of interest to declare.

Funding Sources

The authors received no financial support for the case report, authorship, or publication of this article.

Author Contributions

Sophie Bryde Laursen, Nadja Skadkær Hansen, and Rigmor Højland Jensen have made substantial contributions to conception and design, have been involved in drafting the manuscript and revising the manuscript, and have given final approval for the version to be published. Marianne Wegener, Emil Andonov Smilkov, and Faezeh Nemati Karimooy acquired data, revised, and approved the manuscript. All authors agree to be accountable for all aspects of the work.

Funding Statement

The authors received no financial support for the case report, authorship, or publication of this article.

Data Availability Statement

All data generated or analyzed during this study are included in this article and the supporting files. Further inquiries can be directed to the corresponding author.