Synchronous polyostotic fibrous dysplasia and meningiomatosis: a case report on the challenging treatment for severe intracranial hypertension

Introduction

Fibrous dysplasia was first reported in 1938 by Louis Lichtenstein (1). It is a rare congenital, non-familial, bone disorder in which bone formation and resorption are altered, leading to abnormal growth of expansive fibro-osseous lesions.

Despite being extremely rare, there is growing evidence of an association between fibrous dysplasia and co-existing meningiomas. No known single etiopathological factor explains the coexistence of these tumors, but several theories exist, such as: (I) a basic metabolic error of both tissues during their initial growth period and a blastematic tendency (2); (II) a genetic predisposition; (III) a purely coincidental event; or (IV) environmental influence as an irritating agent for the local proliferation and growth of the other (3). Whichever may be the contributing factor for the coexistence of these conditions, it can only be ascertained through further study. However, there does seem to be a common but undetected influencing factor between the two, making it all the more important to report the rare occasions where they co-exist.

Searching the available literature, we identified only sporadical references of this association (2-6). We report a case that, to the best of our knowledge, is the first one that shows an association with severe refractory intracranial pressure (ICP) demanding neuromonitoring, neurointensive care and an elaborate surgical approach due to the expanding bone lesions. We present this article in accordance with the CARE reporting checklist (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-69/rc).

Case presentation

A 36-year-old female, with a history of neurosurgical assessment during her infancy due to congenital cranial dysmorphia (and subsequent loss to follow-up), presented with new onset headache during the early stages of her second pregnancy (five-years apart). She underwent an imaging protocol that revealed an extensive fibrous dysplasia of the left frontoparietal cranium (Figures 1,2) and multiple extra-axial lesions (suspected meningiomatosis). An abnormal cranial venous drainage pattern was evident, with loss of detectable flow in the anterior half of the superior sagittal sinus, and an ipsilateral compensatory intraosseous and cutaneous network draining into a facial venous complex (Figure 3). Given her condition, the anatomical constraints to any surgical approach and limited symptomatology, the primary option was watchful surveillance.

Figure 1 Imaging studies at diagnosis: T1-weighted contrasted MRI, axial (A) and coronal (B), displaying extensive areas of hyperostotic skull changes overlapping with multiple meningeal-based tumours. MRI, magnetic resonance imaging.

Figure 2 Computed tomography scan image at the time of hospital admission.

Figure 3 Digital subtraction angiogram of the left internal carotid artery (venous phase) confirming the loss of superior sagittal sinus flow in its anterior portion, and the exuberant venous outflow pattern.

Approximately 5 months later, she presented with episodes of right hemiparesis, motor aphasia and psychomotor retardation accompanied by holocranial headache. These events were self-limited but increasing in severity. An urgent head computed tomography (CT) without contrast was unable to reveal new findings and she was first admitted to a neurosurgical ward for a complementary etiological study.

On the third day of her hospital stay, she began showing signs of neurological deterioration, with incremental right hemiparesis and psychomotor retardation. A new head CT showed an accentuation of the edema surrounding one of the known lesions (specifically, a lesser parasagittal meningioma) with secondary mass effect conditioning a diffuse sulcal and basal cistern attenuation with midline deviation and subfalcine herniation. Magnetic resonance imaging (MRI) was subsequently performed (Figure 1), which revealed, when compared to a MRI performed six months prior, an enlargement, loss of enhancement and restricted diffusion (eventually compatible with tumor apoplexy) of that left frontal parasagittal meningioma, with perilesional vasogenic edema and a marked increase in its mass effect, which itself conditioned effacement of the left lateral ventricle, subfalcine herniation and an eight-millimeter midline shift.

As a result of the clinical and imagiological deterioration, the patient was transferred to a Neurocritical Care Unit (NCCU). Upon admission to the NCCU, there was further deterioration of her neurological status, reaching Glasgow Coma Scale (GCS) of 3 with new onset anisocoria. She was then emergently sedated and intubated. An ICP catheter was placed.

Due to the onset of sustained raised ICP, reaching a maximum value of 35 mmHg, the patient underwent medical treatment to manage increased ICP. Boluses of hypertonic saline were initiated with increasing frequency, reaching a minimum four-hour interval, with occasional mannitol bolus, while maintaining sodium levels below 155 mEq/L. A bed elevation of 30° was secured, sedation and analgesia were optimized with a perfusion of propofol, midazolam and fentanyl, with the objective of keeping a Richmond Agitation Sedation Scale (RASS) of −5. Ventilation was optimized, with a PaCO₂ goal of 35 mmHg, allowing for short periods of 30–32 mmHg. Neuromuscular blockade with a rocuronium perfusion and corticotherapy with dexamethasone were initiated.

Despite these measures, maintenance of the ICP at acceptable levels was challenging. The patient showed no autoregulation evaluated with Pressure Reactivity Index (PRx). Bi-spectral index (BIS) values were kept between 30–40 and near-infrared spectroscopy (NIRS) showed an asymmetry, with higher values on the left side (65–70%) in comparison with the right side (50–60%).

She also developed septic shock with multiple organ dysfunction syndrome (MODS) and sustained fever with the need for perfusion of norepinephrine, antibiotics and temperature control, combining diclofenac perfusion with paracetamol and parecoxib boluses, and external cooling methods with cooling blankets and cold saline.

Due to deterioration of her neurological status evaluated with brain multimodal monitoring, the radiological findings and ICP resistance to non-invasive measures, she was then submitted to a craniotomy (Figure 4) aimed at the complete removal of the apoplectic left parasagittal meningioma, in an attempt to reverse the cycle of edema and intracranial hypertension. At this time, the surgical approach was restricted by design, to limit cortical manipulation and venous implications. After the procedure, ICP was controlled but she developed a bilateral pulmonary embolism, confirmed by thoracic CT angiography, with initiation of anticoagulation with unfractionated heparin. An electroencephalography (EEG) done after the surgery also showed severe encephalopathy with major affection on the left side.

Figure 4 Computed tomography scan image after surgical treatment.

Three days later, the patient’s condition worsened once again, with new episodes of extremely high ICP refractory to non-invasive measures, accompanied by pupillary changes. After imaging was unable to identify a new cause and extensive prognostic debate with the family, the need for another surgical intervention, this time with a cranial decompressive rationale, was presumed. The patient was submitted to a large left frontal craniectomy and removal of areas of fibrous dysplasia with adjacent meningioma tissue; through a second lateral approach between the venous intraosseous channels (visible in Figure 1A), a partial removal and excision of another meningioma was accomplished, but the gain in volume achieved throughout the procedure was limited by the lack of meningeal tissue to effectively contain the brain leading to spontaneous parenchymal herniation into the created cavity space. This led to immediate postoperative left frontotemporal ischemia and diffuse hemorrhage within the herniated tissue, and a new balance between the gain in space and an iatrogenic acute injury was established.

After this second procedure, considering the inherent safety limitations of a new surgical approach, it was decided in a multidisciplinary meeting that medical management would be the only way to treat subsequent episodes of high ICP. With occasional episodes of sudden elevation of ICP, reaching a maximum of 79 mmHg, every non-surgical measure to lower ICP was maintained, requiring on several occasions the use of rescue medication, like mannitol and thiopental boluses, and punctual hyperventilation periods.

More than a month since admission, at a time of increase in the interval between osmotherapy boluses, anisocoria resolution, improvement in the NIRS symmetry and an imagiological reduction in cerebral edema, sedation weaning was initiated to ascertain neurological status.

After five days without episodes of intermittent hypoxic (IH) and preserved autoregulation of cerebral blood flow, the ICP catheter was removed. The patient was tracheostomized to facilitate ventilatory weaning.

The patient stayed at the NCCU for a total of 113 days, showing a progressive radiological improvement (Figure 1B), accompanied by a neurological, ventilatory and cardiovascular recovery. She reached a GCS of 15, oriented in space, time, and person, despite a slight dysarthria and a global muscular atrophy. Complete weaning of ventilation was accomplished, eventually being decannulated and requiring solely the nocturnal non-invasive ventilation. Additionally, hemodynamic stability was achieved with complete halting of vasopressor support.

The patient was discharged to the neurosurgical ward, where she remained for another 54 days, managing Intensive Care Unit Acquired Weakness (ICU-AW) and infectious complications associated with the prolonged hospital stay. She was then transferred to a rehabilitation ward, showing remarkable recovery. She was discharged 9 months after the initial event, maintaining a slight generalized muscle weakness and negligible aphasia, being able to maintain a mostly autonomous lifestyle.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Fibrous dysplasia is an uncommon skeletal disorder characterized by dysregulated bone formation and resorption processes, resulting in aberrant proliferation of fibro-osseous lesions with expansive growth tendencies. In its etiology, there is a mutation in the GNAS1 gene that leads to anomalous fibroblasts and excessive function of skeleton progenitor cells (7). This pathological entity can affect either a single bone (i.e., monostotic fibrous dysplasia) or several bones (i.e., polyostotic fibrous dysplasia). The latter is less common, comprising around 30% of all pathological occurrences. In the clinical spectrum of fibrous dysplasia, we should mention the McCune-Albright syndrome that encompasses café-au-lait cutaneous lesions and endocrine defects besides bone abnormalities due to fibrous dysplasia (2,5).

Even though fibrous dysplasia can impact any bone of the human body, craniofacial involvement is present in 27% of its monostotic form and 50% in the polyostotic manifestation of the disease (8). The rate of occurrence of the fibro-osseous lesions in the different craniofacial bones remains a controversial aspect, with reports of the most affected bones being the ethmoid (71%), sphenoid (43%), frontal (33%) and maxillary (29%), and the infrequent occurrences being in the temporal (24%) and occipital bones (5%) (9).

Numerous patients with fibrous dysplasia do not experience any symptoms; however, those who do often manifest symptoms either during childhood or adolescence. Despite this early onset, the diagnosis can be delayed to the adult stage of life due to mild symptomatology, with the diagnosis being performed incidentally when a radiologic exam is done for another motive (10). Clinically, fibrous dysplasia can present itself as bone pain (generally a consequence of incomplete fractures), bone deformities (when attained to the craniofacial region the most common presentation is asymmetry and swelling) and pathological fractures (10). Neurologic deficits may arise with the progression of the disease, particularly in the case of craniofacial bone injury. Headaches are common, and blindness is one of the most feared complications. The latter arises secondarily due to involvement of the orbit, stenosis of the optic canal and optic nerve compression (8,10,11). Nonetheless, however rare, intracranial growth and compression of the subjacent structures can lead to more severe manifestations such as seizures, intracranial hemorrhage and other vascular anomalies, and intracranial hypertension (11).

In the present report, the patient presented left frontoparietal fibrous dysplasia lesions with progressive intracranial growth and concomitant meningiomatosis. The patient ended up developing rapidly progressing neurologic deficits, severe neurological impairment with coma and refractory intracranial hypertension. Granting the concomitant existence of meningioma and fibrous dysplasia is known, to the best of our knowledge, this is the first reported case of concurrent polyostotic fibrous dysplasia and multiple meningiomas coursing with severe refractory intracranial hypertension.

The treatment of fibrous dysplasia is still a debatable issue (8). Since no curative therapeutic option is available, surgery remains the gold standard strategy for treatment (8).

Nonetheless, there is controversy about the need for radical surgery or whether a more conservative surgical approach should be the choice of therapy, especially amongst asymptomatic patients and in those with no evidence of disease progression. It is important to mention that the broad clinical manifestation can prompt different treatment approaches. Ultimately, the best treatment plan is one tailored to the individual (8).

In this reported case, surgical intervention was required due to intractable intracranial hypertension (not only to remove the most problematic meningiomas but also to release hyperostotic areas of fibrous dysplasia) but was also a promotor of iatrogenic injury that we tried to account for. Given the obvious lack in previous literature and the patient’s specific anatomical features, considerable ethical concerns were part of the therapeutic equation and shared with the family throughout the process (12).

We also believe this case highlights the vital importance of interdisciplinary collaboration between medical specialties in the neurocritical field, where a tailored surgical approach, continuous effective management of the severe intracranial hypertension and repeated ensuing medical complications were key to the patient’s neurological recovery.

Conclusions

The present case report presents a unique and complex instance of polyostotic fibrous dysplasia with concomitant multiple meningiomas associated with severe, refractory intracranial hypertension. The patient’s condition highlights the challenges in managing such rare and elaborate cases, underlining the need for a multidisciplinary approach to treatment. Due to the rarity of the condition, the concurrent meningiomas, and the ensuing of elevated intracranial hypertension the patient’s required advanced neuromonitoring, intensive neurocritical care, and multiple surgical interventions.

The progressive neurological decline followed by intractable ICP requested of the assistant team a dynamic treatment approach that evolved from initial conservative management to aggressive non-surgical measures, ending up with more aggressive and extensive surgical interventions.

The case underscores the importance of tailored treatment plans, particularly in instances where conventional approaches are insufficient to solving the patient’s problem and preserve their life and a life with quality. The patient’s recovery, despite the arousal of medical complications, was ultimately successful, validating the value of customized surgical strategies pooled with methodical medical management.

In addition, the report contributes to what we believe to be valuable insights to the narrow available literature on the interplay between fibrous dysplasia and meningiomas, consequently emphasizing the need for awareness and careful management of ICP in such patients. It also exemplifies the much-needed space for interdisciplinary collaboration in addressing complex neurocritical conditions, in such a way that optimizes not only care but also patient outcomes.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-69/rc

Peer Review File: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-69/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-69/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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