A Case of Atraumatic, Streptococcal Pneumocephalus: A Rare Complication of Influenza B Infection

Background

Influenza is a disease of the respiratory tract diagnosed at any time of the year, but it is most common during the fall and winter [1]. Complications directly caused by influenza manifest in some patients, including acute respiratory distress syndrome, myocarditis, rhabdomyolysis and encephalitis [2]. Secondary bacterial infections such as bacterial pneumonia also develop and typical bacterial species involved are Staphylococcus and Streptococcus [3]. An advanced complication like pneumocephalus after a diagnosis with influenza B virus infection is unusual. Pneumocephalus, which is air within the brain parenchyma, is frequently associated with head trauma, intracranial pathologies or neurological surgery [4,5]. Direct etiologies related to infections are less prevalent and require aggressive management to reduce mortality. Here, we describe a rare complication of influenza B virus infection by delineating a case of bacterial meningitis and pneumocephalus in a patient with influenza B virus infection.

Case Report

A 51-year-old woman with a past medical history of iron deficiency anemia and morbid obesity presented to the Emergency Department in early winter because of worsening mental status over seven days. She was unvaccinated against influenza and was diagnosed with influenza a few days earlier at an urgent care clinic. A few hours before presentation she was retching and unable to talk. A family member denied any recent history of head trauma or surgery. Her vital signs revealed a temperature of 104.4°F (40.2°C), pulse rate of 123 beats per minute, blood pressure of 160/81 mmHg, respiratory rate of 20 cycles per minute, and oxygen saturation of 95% on room air. Her Glasgow Coma Scale was nine. On physical examination her head inspection was normal, pupils were equal and reactive to light, she had no nuchal rigidity, and Brudzinski sign was negative. The rest of the examination was unremarkable. She was alert and moved all extremities but was not following commands.

Laboratory results revealed she was positive for influenza B antigen but because of the possibility of an acute intracranial pathology she had an urgent computed tomography (CT) of the head (Figure 1). It revealed pneumocephalus in the left parietal occipital vertex, acute-on-chronic sinusitis, and left middle ear fluid with left mastoid air cell effusion. A chest x-ray was unremarkable. Other laboratory investigations were significant for a white cell count of 18 400/ul with neutrophil percent of 91.6, international normalized ratio of 1.26, lactic acid of 2.3 mmol/L, hemoglobin A1c of 7.9%, and serum glucose of 266 mg/dL. A urinalysis revealed glucose of greater than 1000 mg/dL and ketones of 80. An electrocardiogram demonstrated sinus tachycardia with occasional premature ventricular complexes.

Meningitis was highly suspected and she was started on empiric antibiotics of intravenous ceftriaxone (2 gm every 12 hours), intravenous meropenem (2 gm every 8 hours), and intravenous vancomycin (1 gm every 12 hours). She was also treated with intravenous dexamethasone (10 mg every 6 hours), a full course of oral oseltamivir, and parenteral insulin. Subsequent cerebrospinal fluid (CSF) analysis revealed a hazy appearance, a white count of 387/mm3, a red count of 409/mm3, glucose of 90 mg/dL, and a total protein of 174.6 mg/dL. The CSF microbiology was positive for Streptococcus pneumoniae antigen, but the Gram stain was negative and the CSF did not grow any organisms. A blood culture grew Streptococcus pneumoniae. She decompensated mentally and had multiple seizures after a few days, which required intubation four days later for airway protection. She was also started on levetiracetam for seizures. Fortunately, she improved clinically and she regained her mental state to her previous baseline without residual neurological deficits. A CT head (Figure 2) was repeated 15 days after presentation showing complete resolution of the pneumocephalus.

Discussion

Influenza virus infections are most prevalent during the fall and winter [1]. The most common types are influenza A and B, belonging to the Orthomyxoviridae viruses [6]. Between 2000 and 2018, influenza B was the main cause of influenza in about 25% of cases globally [7]. It often infects the respiratory tract and it has been linked to several complications like myocarditis, encephalitis, ophthalmitis, and acute kidney failure [2].

Secondary bacterial infections can also manifest in patients with influenza. Streptococcus pneumoniae, Staphylococcus aureus, and Hemophilus influenza have been identified in causing bacterial pneumonia in patients with influenza [3]. Nonetheless, further complications due to secondary bacterial infections have not been well documented.

Our patient had a distinctive situation because she developed secondary streptococcal bacteremia and meningitis with subsequent pneumocephalus after a recent diagnosis of influenza B virus infection. A literature search resulted in articles that discussed pneumocephalus but only a few implicated Streptococcus pneumoniae. Some of the cases of pneumocephalus were due to head traumas or neurosurgical interventions [4,5,8,9]. Other causes were secondary to intracranial anatomic pathologies and infections [10–13]. Based on the clinical manifestations and diagnosis of our patient, we searched for articles about pneumococcal meningitis with pneumocephalus, with emphasis on influenza diagnosis. In a 2019 case report by Barry et al., the patient developed pneumococcal meningitis with pneumocephalus in the setting of mastoiditis and sinusitis, but the pneumocephalus resolved after treatment with antibiotics [13]. In another case report, the patient was also treated with antibiotics against pneumococcal pneumocephalus in the background of sinusitis, although there was no laboratory evidence of Streptococcus pneumoniae [14]. Other case reports we reviewed were similar to the ones that have been discussed [15,16]. Our patient also had CT evidence of acute-on-chronic sinusitis with mastoid effusion, but a diagnosis with influenza B infection makes our case unique.

We searched PubMed and Google Scholar for articles on pneumocephalus development in the context of influenza, using the keywords “pneumocephalus”, “flu”, and “influenza”. However, just one case was reported where pneumocephalus in a 9-year-old boy was determined to be the result of influenza, but no laboratory evidence of influenza was documented in the article [17]. Pneumocephalus arises because of an entrapped air that moves from outside into the cranial cavity or when CSF loss causes negative intracranial pressure [18,19]. Our patient was diagnosed with influenza at an urgent care center. Her mental state deteriorated, prompting a visit to our medical center, where clinical evaluation revealed influenza B infection with pneumococcal meningitis and pneumocephalus.

We believe a recent diagnosis with influenza was the potentiating factor that eventually led to pneumocephalus. Vaccination against the influenza viruses and recognition of influenza complications and early treatment are important in preventing mortality. We believe our case report is the first to present streptococcal meningitis with resulting pneumocephalus in a patient with evidence of influenza B virus infection. Our patient was managed with antibiotics, and a repeat CT scan of the head showed complete resolution. Our report emphasizes the need to continue to educate patients about the benefits of influenza vaccination. Clinicians should always keep in mind that a superimposed complication from secondary bacterial infections in patients with influenza virus infection is not limited to the respiratory system.

Conclusions

Atraumatic pneumocephalus is a rare complication of bacterial infections in a patient with influenza. Our search of the literature revealed just a few cases in which Streptococcus pneumoniae meningitis resulted in pneumocephalus, and none of the patients had a diagnosis of influenza. Furthermore, only one case report revealed pneumocephalus as a complication of influenza; however, laboratory evidence of influenza was not reported in the case report. Early recognition and treatment help prevent mortality. Emphasis on vaccinations against influenza is an important preventive measure that must be promoted by clinicians.