Bacterial Meningitis Associated with Pituitary Macroadenoma : Systematic Review

Introduction Bacterial meningitis complicates rarely pituitary macroadenomas. The aim of our systematic review is to study the features of the association between bacterial meningitis and pituitary macroadenoma. Methods We conducted a literature search in both MedLine and Google Scholar database from 1967 to October 2016 and reviewed all cases described of the association between bacterial meningitis and pituitary macroadenoma apart from any surgical act and without pituitary apoplexy. Results We found 14 articles describing 16 patients aged of 22-69 years old with a male predominance (sex ratio 4.3). Two patients (12.5%) had a well-documented clinical history of pituitary macroadenoma prior to the diagnosis of bacterial meningitis. Rhinorrhea has been found as the most common symptom through six patients (37.5%). Through the CSF culture, bacterial meningitis among patients suffering of pituitary macroadenoma commonly was due to Streptococcus pneumoniae. The examination in 18.75% of cases revealed signs related to pituitary macroadenoma (ophthalmoplegia and blindness). Six patients (37.5%) had received a treatment by dopaminergic agonist alone and 4 patients (25%) were treated with dopaminergic agonist associated with surgical treatment. Surgical treatment consisted of closure of the osteomeningeal breach in 12.5% (2/16) and tumor resection in 31.25% (5/16). Three patients (18.75%) had benefited tumor resection without prior agonist treatment. The mortality was 12.5% (2/16). Conclusion Our systematic review shows that bacterial meningitis represents a rare initial symptom leading to the diagnosis of invasive pituitary macroadenoma. DOI : 10.14302/issn.2470-5020.jnrt-17-1503 Corresponding author Dr TOUDOU DAOUDA Moussa, Department of Neurology, Hassan II University Teaching Hospital, Sidi Harazem Road, PO Box 1835, Atlass, Fez, Morocco and Department of Medical and Medical Specialties, Hospital national de Niamey, boite postale 238, Niamey, Niger. Email: moussatoudou@gmail.com


Introduction
Pituitary macroadenomas (PM) are usually revealed by endocrine disorders such as galactorrhea, menstrual disorders, decreased libido, sexual impotence, gynecomastia, or headaches and visual troubles [1].
Bacterial meningitis (BM) is a rare complication of the PM apart from any surgical act and without pituitary apoplexy with few cases described in the literature.The aim of our systematic review is to study the features of the association between BM and PM.

Methods
We conducted a literature search in both MedLine and Google Scholar database from 1967 to October 2016 using the following keywords: "meningitis'' and "pituitary adenoma'' or "meningitis'' and "macroprolactinoma'' or "meningitis'' and "pituitary macroadenoma''.At the end of our literature search, we found three case series and 16 case reports describing a total of 22 cases of BM complicating a PM apart from any prior surgical act and without pituitary apoplexy (Table I).We included in this systematic review case reports and case series in English and French language that also had data available.We did not include the articles that are not written in English or French language and those that did not have data available.Thus, among the 19 articles found, 14 articles were extracted, examined and included in this systematic review.For each article, the following informations were extracted: age, sex, past medical history, clinical presentation, imaging results, cerebrospinal fluid (CSF) results, anatomopathology findings, treatment and evolution.

Results
Among the 22 cases of BM complicating a PM apart from any prior surgical act and without pituitary apoplexy, our systematic review had included 16 cases that had available data.The most common clinical sign was fever (93.75%), followed by nuchal stiffness (75%; Table II).
The cerebral CT scan was performed for all patients and 87.5% (14/16) among them underwent cerebral magnetic resonance imaging (MRI) (Table II).
The cerebral CT scan revealed PM in the form of an invasive intra-and suprasellar lesional process in all patients (100%).The cerebral MRI was performed as a complement to the cerebral CT scan and confirmed the

Discussion
BM is a rare complication of the PM apart from any prior surgical act and without pituitary apoplexy.
Our systematic review had analyzed all the reported cases of the association between BM and PM, which had The clinical presentation was mainly dominated by signs of BM: nuchal stiffness (75%), headaches (50%), vomiting (37.5%), fever (93.75%), and altered consciousness (56.25%).Clinical signs probably related to the PM were decrease of visual acuity (6.25%) and ophthalmoplegia (12.5%).The visual troubles could be explained by compression of the optochiasmatic tract [9].Ophthalmoplegia is the consequence of the invasion or compression of the oculomotor nerves in the cavernous sinus by the PM [9].The disturbance of consciousness could also be a sign related to PM by endocrine disorders especially the lackness of corticotropic axis [1,5,9,10].
In terms of physiopathological, the occurrence of BM could be explained by the fact that PM destroy the sellar floor and invade the sphenoid sinus and the meninges creating an osteomeningeal breach with leakage of the CSF (rhinorrhea) responsible for the bacterial infection of the meninges and cerebral structures [9].The rhinorrhea can precede the BM [2, 4 -8] or even be totally unnoticed examination and visual field [11], or in case of treatment failure with dopaminergic agonists with persistence of hyperprolactinemia [14].In our study, the histological study has been realized in 2 patients with suspicion of invasive PM to the cerebral CT scan and in whom a cerebral MRI has not been performed [4,6].
Streptococcus pneumoniae was the most common causative agent of BM in our study (71.4%).
The other germs were streptococcus oralis (14.3%) and streptococcus mitis (14.3%).This great predominance of streptococcus pneumoniae is due to the fact that this bacterium is very common in the respiratory tract (especially the nostrils) even in man being healthy.
In our study, the minimum value of prolactin is

[ 1 - 3 , 9 -
14].The absence of rhinorrhea in the majority of patients (62.5%) could be explained by the fact that the osteomeningeal breach was clogged by the PM [9, 10].MRI remains the first choice to perform brain imaging not only in the diagnosis of the PM but also in the exploration of its anatomical relationships with neighboring structures.Cerebral MRI, coupled with the prolactin assay, is sufficient to establish the diagnosis of invasive PM.The histological study is performed only when a tumor resection has been performed in the case of compressive PM with visual troubles or disturbed ophthalmologic examination especially fundus 200ng/mL which is a specific biological element in favor of the diagnosis of macroprolactinoma.Only one case of transient elevation of ACTH with hypercortisolemia associated with hyperprolactinemia was observed in our study[14].On the other hand, we have underlined 4 cases of panhypopituitarism associated with hyperprolactinemia[1,5,9,10].The panhypopituitarism would probably be secondary to a compression of the pituitary stem disconnecting the pituitary gland, which is a rare situation in the PM.Dopaminergic agonists (cabergoline or bromocriptine) represent the first choice treatment of macroprolactinomas without alteration of the ophthalmic examination (fundus examination and visual field).In our study, dopaminergic agonists had allowed a reduction of the size of the PM in 8 patients [1, 2,3, 5, 8, 9].On the other hand, tumor resection was initially performed in 4 patients[4,11,12,14], among which one patient had received a treatment by dopaminergic agonist in a second time[12].One patient received Table III: treatments and outcomes of the 16 patients.

Table I :
reported cases of bacterial meningitis complicating a pituitary macroadenoma apart from any previous surgical intervention and without pituitary apoplexy.

Table II :
epidemiological, clinical and paraclinical features of the 16 patients.