We present a unique case of bacterial encephalitis in a 79-year-old female due to progression of medication-related osteonecrosis of the jaw. The occurrence of this life-threatening neurologic condition following the expansion of medication-related osteonecrosis of the jaw is an extremely rare finding, and we know of no other previously reported cases. The case history, differential diagnosis, proposed mechanism and management of this fatal complication is discussed.
Medication-related osteonecrosis of the jaw (MRONJ) is described as a progressive bone destruction in the maxillofacial region that can occur after exposure to certain antiresorptive or antiangiogenic agents.
To the best of our knowledge, only two cases of MRONJ extended beyond the maxilla to the skull base have been reported in previous medical literature.
We herein report the first case of MRONJ in which its progression from the initial maxillary site to the nearby skull base led to the development of bacterial encephalitis.
The possibility of life-threatening neurological complications must be constantly acknowledged by the oral and maxillofacial surgeon when treating advanced maxillary MRONJ patients.
Medication-related osteonecrosis of the jaw (MRONJ) is described as a progressive bone destruction in the maxillofacial region that can occur after exposure to certain antiresorptive or antiangiogenic agents [ ].
Ever since the first cases of MRONJ were documented in 2003, there have been copious reports of this condition found among the mandible and/or the maxilla [ ]. However, only a limited number of cases of MRONJ extended beyond the maxilla to the skull base have been reported in previous medical literature, and its potential threat to the central nervous system remains elusive [ ].
In the present paper, we herein report the first case of MRONJ in which its progression from the initial maxillary site to the brain led to the development of bacterial encephalitis.
Presentation of case
A 79-year-old female was referred to the oral and maxillofacial department for evaluation of constant spontaneous pain of her right maxilla. The pain had first occurred following the extraction of her right maxillary second molar, performed at a local dental clinic in August 2017. The patient had a history of osteoporosis, which had been treated with weekly oral administration of 35mg risedronate sodium hydrate for the past 10 years . No significant history of smoking, alcohol use, or other medical comorbidities was noted. Subsequent clinical and radiographic examinations revealed bone necrosis of the relevant region. In January 2018, sequestrectomy of the osteolytic lesion was performed at another hospital, resulting in temporary symptom relief.
In December 2018, the patient was referred to our hospital again due to recurrent pain of her right posterior maxilla. A chronic intraoral fistula formation with blood and pus exudation was noted. Cone-beam computed tomography (CBCT) scans revealed significant necrosis of the right posterior maxilla extending to the medial wall of the maxillary sinus, and subsequent thickening of the sinus mucosa due to infection ( Fig. 1 ). Whole body bone scans demonstrated increased Tc-99 m MDP activity along all the walls of the right maxillary sinus ( Fig. 2 ).
The final diagnosis of MRONJ stage III accompanied by relevant right-sided chronic maxillary sinusitis prompted surgical treatment under general anesthesia along with concomitant use of amoxicillin-clavulanate and clindamycin. In conjunction with thorough surgical debridement of all the maxillary sinus walls, a partial maxillectomy, extended to include the pterygoid plate, was performed , thus yielding successful removal of all the inflammatory tissues and a complete alleviation of respective symptoms. Post-operative recovery was uneventful, and the patient was followed up periodically with no specific signs of infection.
However, on January 18th, 2020, the patient was admitted to the department of neurology after developing myalgia, high fever (38.0 °C) and rapid deterioration of her mental status that had initiated less than 24 hours prior to her admission. On presentation, the patient was stuporous with a Glasgow Coma Score of 10 (E3, M5, V2). Cerebrospinal fluid analysis revealed pleocytosis with a white blood cell count of 396 cells/mm 3 , elevated protein content of 312.8 mg/dl, and a slightly decreased glucose level of 30 mg/dl. PCR for the herpes simplex virus 1 and 2, Epstein-Barr virus, varicella zoster virus, and cytomegalovirus were all negative. However, the CSF culture was positive for methicillin-resistant staphylococcus epidermidis (MRSE), and therapeutic drug monitoring of vancomycin was thus initiated at a steady state with a target trough concentration of 15–20 mcg/ml along with intravenous administration of ceftriaxone and ampicillin. An ill-defined osteolytic lesion with bony sequestrum in the right greater wing of sphenoid could be noted on the brain CT scans ( Fig. 3 ). A diffusion-weighted magnetic resonance imaging (DW-MRI) of the brain demonstrated prominent pachymeningeal enhancement along with high-signal fluid collection and swelling of the right fronto-temporal subdural area ( Fig. 4 ). Based upon these findings, the patient was diagnosed as bacterial encephalitis.