A 65-year-old male patient was admitted to the hospital because of fever and headache lasting for 5 days. The patient long had poor oral hygiene and 4 years ago, the patient underwent implantation of mandibular dentures. Fever usually occurred at noon and was generally under 38 C. In addition, the patient was presented with persistent heartburn, anorexia, asthenia, and night sweats. Blood routine examination revealed that the white blood cell (WBC) count was 12.08 x 109/L (normal range, 4-10 x 109/L) with neutrophil leukocytosis of 71.1%. No significant abnormality was found in the heart or lungs of the patient. Then the patient was admitted to the Department of Infectious Diseases.
On admission, physical examination showed poor mental status and subtle abduction limitation in the left eye without other neurological signs or symptoms. The patient underwent a lumbar puncture on the day of admission. Cerebrovascular fluid (CSF) showed a normal WBC count (4/mul, reference range 0-8/mul), mildly increased protein level (0.6 g/L, reference range 0.15-0.45 g/L), reduced chloride levels (114.6 mmol/L, reference range 118-132 mmol/L), and normal glucose levels (3.97 mmol/L, reference range 2.5-4.2 mmol/L; Table 1). Pre-antibiotic blood culture was taken with a negative result. Additional laboratory examinations, such as serology testing for HIV, hepatitis B/C, syphilis, rheumatic diseases, and tumor markers, were normal. Cranial magnetic resonance imaging (MRI) was normal (Figure 1A), and there was no evidence of intracranial aneurysm on brain magnetic resonance angiography (MRA; Figure 1B). The diagnosis of viral encephalitis was considered and treatment with intravenous acyclovir (10 mg/kg) was initiated and continued every 8 h. However, with frequent low fever, the illness was not well-controlled. Considering the likelihood of bacterial infections, ceftazidime (2 g every 12 h) was given on the third day of admission. On hospital day 7, the patient developed significant diplopia and weakness in the right upper extremity with a brain MRI showing acute multiple cerebral infarcts in the left cerebral hemisphere (Figures 1C,D). On the same day, the patient underwent a lumbar puncture once more, and the macroscopic appearance of the CSF was slightly yellow with a pressure of 190 mmH2O (normal range, 80-180 mmH2O). CSF results are shown in Table 1. The patient was diagnosed with intracranial infection and transferred to the Department of Neurology.
Neurological examination showed drowsiness, left abducens nerve palsy, degree 4 muscle strength in right upper limb, and neck rigidity (+). The culture of bacteria and mycobacterium tuberculosis and the detection of viral nucleic acid for retrovirus, herpes virus 1 and 2, rhinovirus, Epstein-Barr (EB) virus, and cytomegalovirus in CSF were negative. Additionally, the brucellosis agglutination test, Japanese encephalitis virus antibodies detection, T cell spot test for tuberculosis (T-SPOT), tuberculin test, and mycobacterium tuberculosis/rifampicin resistance test (X-pert) were also negative. Since our patient had such signs, the diagnosis of tuberculous meningitis was considered. The patient was administered an anti-tuberculous therapy that included isoniazid (0.6 g once daily), rifampicin (0.45 g once daily), ethambutol (0.75 g once daily), and pyrazinamide (0.5 g three times daily). In the following days, the body temperature returned to normal, but the patient still had intermittent headache. Compound codeine phosphate and ibuprofen sustained release tablet (0.2 g/13 mg two times daily) were added to control the headache. On hospital day 16, the patient developed frequent nausea and vomiting. The mental state of the patient also became very poor yet no fever, abdominal pain, or blurred vision were observed. Physical examinations, laboratory tests, and abdominal computed tomography (CT) scans could not reveal the cause of the patient's deterioration. We suggested that it might be the side effects of anti-tuberculosis drugs. Ondansetron (8 mg) and metoclopramide (10 mg) were intravenously utilized for anti-emesis. His gastrointestinal symptoms were improved. However, the mental state was getting even worse. On hospital day 25, the patient was presented with near-complete left oculomotor nerve palsy with blepharoptosis and dilated pupils on the left side. CSF results showed an increased WBC count (300 x 106/L) with 63% mononuclear cells (Table 1). Cranial CT revealed significantly increased low-density shadow in the left frontal, temporal, and parietal lobes (Figures 1E-G). As a result of the disease progression, the patient was transferred to a superior hospital.
Detailed neurological examinations and evaluations were performed on this patient again. The MRI (Figures 1H,I) and MRA (Figure 1J) re-examination demonstrated that the lesions in the left cerebral hemisphere were increased significantly, and a cerebral aneurysm was formed in the intracavernous segment of the left internal carotid artery (ICA). In addition, the sphenoid sinus mucosa was thickened. Taking the possibility of bacterial infection into consideration, the patient was treated with ceftriaxone (2 g every 12 h). On hospital day 28, the patient underwent a lumbar puncture examination again. CSF results are shown in Table 1. Metagenomic sequencing of viral and bacterial genomes from this patient's CSF sample was performed with a negative result. Unfortunately, the patient fell into a coma the following day and was admitted to the intensive care unit (ICU). Head MRI showed a markedly enlarged size of the left temporal lesions with abscess formation and bleeding, accompanied by peripheral ring-shaped enhancement (Figures 1K,L). Due to the patient's poor condition, the anti-infection regimen was adjusted to an intravenous drip of biapenem (0.3 g every 12 h) and vancomycin (1 g every 12 h). The patient was gradually recovered consciousness within the next 7 days. On hospital day 37, brain MRI showed a decreased size of the left temporal lesions but with perifocal evident edema (Figure 1M). To further clarify the nature of the intracranial lesions, the patient was transferred to the Neurosurgical Department to perform the needle biopsy with the assistance of real-time neuro-navigation on hospital day 38. The next day, this patient underwent the procedure, and the surgical specimen was sent for smear, culture, and deoxyribonucleic acid sequencing. According to the sequencing results, the patient was diagnosed with bacterial meningitis caused by a mixed infection of oral microflora dominated by anaerobes, such as Fusobacterium nucleatum (69.79% relative abundance), Prevotella intermedia (20.77% relative abundance), Bacteroides uniformis (1.35% relative abundance), Campylobacter rectus (1.26% relative abundance), Oral peptostreptococcus (0.08% relative abundance), Streptococcus constellatus (0.02% relative abundance), Torque teno virus 15, and Treponema socranskii. The anti-microbial regimen (biapenem combined with vancomycin), which could sufficiently cover anaerobe, was used continuously. For the poor oral hygiene, the patient received a detailed oral examination and nursing intervention. In the following days, the overall condition of the patient was significantly improved, but there was still a loss of appetite. However, the clinical symptoms worsened from the hospital day 53. The patient was presented with severe lethargy, headache, nausea, and vomiting. Repeat brain MRI showed that the lesions and edema of the left temporal lobe were improved, but hydrocephalus became even worse (Figures 1N,O). The patient was transferred to the Department of Neurosurgery of our hospital at the insistence of family of the patient on hospital day 58.
Neurological examination revealed consciousness disturbance with a Glasgow Coma Scale (GCS) of 9 (E2V2M5), right hemiplegia, left eyeball fixation, pupil dilation with ptosis on the left side, and stiffness in the neck. Cranial CT showed intraventricular extension and hydrocephalus (Figure 1P). We considered that the aggravation of this patient's disease might be related to the progressive hydrocephalus. Then, the patient underwent ventriculostomy on hospital day 59. The anti-infection therapy regimen previously described was changed to the combination of meropenem (2 g every 8 h) and linezolid (0.6 g every 12 h). The clinical symptoms of the patient were improved significantly, and the patient gradually regain consciousness. On hospital day 85, this patient underwent a ventriculoperitoneal shunt operation, and then the mental state of the patient improved further. On hospital day 97, when the patient was discharged, patient was able to walk with assistance and engage in simple conversation but showed a loss of appetite and significant weight loss.
In the 1-month follow-up, the patient could walk without the assistance of a cane or brace. However, severe neurological deficits, such as diplopia and right hemiplegia, still existed. To prevent disease recurrence, we suggested that the patient should maintain good oral hygiene and regular follow-up at the stomatology clinic. Because of the high risk of rupture and mortality of the patient's intracranial aneurysm, surgical treatment was advised. However, the patient refused further examination and treatment for financial reasons. Regular follow-ups will be carried out for our patients. The clinical course is summarized in Figure 2.