Rapidly fatal pneumococcal meningitis following non-penetrating traumatic brain injury

Abstract

A previously healthy young man presented to hospital with severe traumatic brain injury following a motor vehicle collision. Within 24 hours of admission, and despite antibiotic coverage, he developed a fever. On the second day, the source of infection was discovered to be purulent pneumococcal meningitis. At 48 hours post-accident, he developed brain-stem death without evidence of raised intracranial pressure or trans-tentorial herniation. Initial CT scans of the head were essentially normal, but early repeat scans revealed evidence of pneumocephalus and possible frontal bone fracture. Current recommendations do not make room for targeted antibiotic prophylaxis in traumatic brain injury patients with traumatic skull fracture. We argue that our case demonstrates the need for aggressive targeted antibiotic prophylaxis in the presence of certain features such as frontal or sphenoid bone fracture and pneumocephalus.

Background

This case illustrates that the presence of pneumocephalus on CT head following traumatic brain injury should prompt a search for the origin of the air. If there is evidence of frontal or sphenoid sinus communication with the intracranial cavity, aggressive antibiotic prophylaxis with centrally active antibiotics, may prevent devastating infectious complications.

This approach is not supported by current recommendations. We contend, however, that the location of the fracture, and associated features such as pneumocephalus, are additional risk factors which should prompt a different decision matrix in traumatic brain injury patients.

Accepted risk factors for fulminant pneumococcal meningitis do not currently include sinusitis or trauma. It is possible that should these risk factors be included in the broader understanding of pneumococcal disease, this may affect outcomes for this particular patient group.

The mechanism of cerebral injury with pneumococcal disease is currently unclear. Our patient developed brainstem death without evidence of markedly raised intracranial pressure, nor transtentorial herniation on CT head. Scattered case reports do exist; our case adds to the literature in terms of understanding the pathophysiological process involved in pneumococcal infections of the brain.

Case presentation

A 19-year-old man was admitted to the trauma intensive care unit (TICU) of a tertiary referral hospital. He had been involved in an unwitnessed motor vehicle collision and had been ejected from the vehicle. He was found unresponsive by the emergency medical services with a Glasgow Coma Score (GCS) of 3, left pupil dilated at 6 mm with no reaction, and right pupil at 4 mm, briskly reacting. He appeared to have sustained a head injury and multiple long bone fractures.

He was intubated at scene, and admitted to the emergency department 45 min later. An ‘AMPLE’ (allergy, medications, past history, last meal, events leading to accident) history was negative for any medical conditions or recent illnesses. His family reported that he had been fit and well with no upper respiratory tract symptoms. A search of the regional electronic patient record was also negative for any contact with health providers.

On admission to the emergency department, the advanced trauma life support primary survey revealed an intubated patient with clear lung fields and a respiratory rate of 30 breaths/min, a pulse rate of 120 beats/min and a blood pressure of 149/92 mm Hg with normal cardiovascular signs. His abdomen was soft and lax with no signs of pelvic injury or occult bleeding. His GCS was E1M1Vt with unequal but reactive pupils (right 3 mm, left 4 mm). His temperature was 37°C. Note was also made of a scalp laceration. There was no clinical evidence of a cerebrospinal fluid leak.

He was considered stable enough to undergo imaging studies, and a PAN-CT scan was performed.

This initially reported a large left parietal region subgaleal hematoma overlying a thin rim of extra-axial haematoma (with tiny pneumocephalus). Fractures of the left zygomatic arch, lateral and inferior walls of the left orbit (with orbital emphysema), lateral wall of the left maxillary sinus and sphenoid sinus, were noted. There was a non-displaced fracture of the left frontal bone (figure 1).

Figure 1.

Initial CT head.

CT scan of the chest showed multiple rib fractures with bilateral airspace opacities suggesting pulmonary contusion or aspiration. The right clavicle was fractured in the middle third.

CT of the abdomen and pelvis showed no abnormality.

Admission blood work is show in table 1. His white blood cell count (WBC) was 17.6×10⁹/L with a 77% neutrophilia. The rest of his blood work was normal.

Table 1.

Laboratory results

Blood parameter	Day 0	Day 1	Day 2	Day 4	Day 5
WBC (109/µL)	17.6	14.8	30.9	26.7	21
Neutrophils	13.5	11	28.2	24.8	17.4
C-reactive protein (mg/L)		61	170
Procalcitonin (ng/mL)		1.59	12.91

WBC, white blood cell.

He was treated with mechanical ventilation, sedation and anti-epileptic medication. He received tetanus toxoid and a bolus dose of cefepime 2 g 20 min post admission to hospital.

He was admitted to the TICU for observation 2.5 hours post hospital admission. At the time of admission and off sedation, he was found to have a GCS of E1M4Vt (6). His right pupil was recorded as 3 and reactive, with the left 4 and fixed. He was sedated with Fentanyl and Propofol.

Follow-up examination 6 hours post ICU admission revealed an improving GCS of E1M5Vt (7) with unequal but reactive pupils.

Day 1 postadmission, a follow-up CT scan of the head showed a small increase in a left fronto-temporal hematoma, and significantly progressed pneumocephalus (figure 2). There was no midline shift or mass effect. The neurosurgical plan was to wean sedatives and extubate the patient. The WBC count was 14.8. The pupils had normalised to 3 mm and reactive. X-ray of the lungs showed complete resolution of the airspace opacities. Gas exchange was normal.

Figure 2.

CT day 1 with pneumocephalus.

Day 2 post admission the patient spiked a fever of 39°C at midday. The WBC count was 30.9 with a 94% neutrophilia. The C-reactive protein count was 170 and procalcitonin level was 12. His pupils became unequal and unreactive. Phenytoin was administered and an urgent repeat CT head revealed newly dilated ventricles (figure 3). His clinical condition deteriorated with pupils rapidly dilating to 7 mm bilaterally with no reaction. He became haemodynamically unstable.

Figure 3.

CT day 2 with dilated ventricles.

The patient was shifted directly to the operating room for life-saving external ventricular drain (EVD) insertion.

At operation, a right frontal EVD was inserted. Cloudy cerebrospinal fluid (CSF) came out under high pressure. Fluid was sent for laboratory investigations including microscopy and culture. Table 2 lists the positive microbiological results from day 2.

Table 2.

Microbiology

Culture type	Day 2
Sputum	Streptococcus pneumoniae (fully sensitive)
Blood	S. pneumoniae (fully sensitive)
CSF	St. pneumoniae (fully sensitive) CSF glucose<0.3 CSF protein 2.58

CSF, cerebrospinal fluid.

Pupils remained fixed and dilated after surgery.

He was started on meropenem 2 g every 8 hours and vancomycin 1.5 g every 8 hours.

All sedative agents were stopped in the evening of the second day of admission. He developed profound diabetes insipidus with marked polyuria, and a sodium elevation to 172 mEq/L. This was treated with desmopressin and free water replacement.

In light of initial uncertainty regarding the source of the pneumococcal sepsis, an echocardiogram was requested to exclude endocarditis. A transoesophageal echocardiogram was negative for valvular pathology or vegetations, and was normal in terms of chamber sizes and biventricular function.

An MRI of the brain revealed diffuse brain grey matter oedema with effacement of the basal cisterns and extra-axial cerebrospinal fluid spaces (figure 4). Fullness of the posterior fossa and foramen magnum with bilateral cerebellar tonsillar herniation was noted. There was global brain and brainstem diffusion restriction with absent intracranial blood flow signal suggestive of global ischaemic/hypoxic brain injury.

Figure 4.

MRI brain.

He was declared brain dead on the seventh day post admission, once electrolyte and temperature abnormalities had been corrected.

Differential diagnosis

The onset of streptococcal pneumoniae meningitis in this patient occurred after admission to the hospital. The source of the streptococcus was either pulmonary, upper respiratory or haematogenous spread. Collateral history was negative for pre-existing illness.

There was no evidence on clinical or imaging studies of a source of sepsis apart from the respiratory tract. Opacities on CT lung at time of admission could suggest aspiration pneumonia. However, the patient received a broad-spectrum antibiotic at time of admission, and respiratory dynamics were never consistent with pneumonia. Follow-up chest-XR studies from day 1 were normal. A transesophageal echocardiogram excluded endocarditis.

The rapidity of onset of overwhelming sepsis, in addition to the presence of progressive pneumocephalus, strongly suggests a sinus origin for the ingress of bacteria into the brain. Both the sphenoid and frontal sinuses were potentially colonised with bacteria, and are in close proximity to the intracranial contents (figure 5).

Figure 5.

Sinus relationship to intracranial contents (©2012 Terese Winslow, U.S. Govt. has certain rights).

The onset of rapid brainstem death following fairly innocuous initial and 24-hour follow-up CT head, suggests an alternative method of progressive brainstem death, apart from the original traumatic brain injury. Follow-up MRI day 7 confirmed diffuse anoxic injury, not evidenced prior to the onset of devastating meningitis.

Treatment

Initial treatment was with sedation and supportive measures for severe traumatic brain injury, including hypertonic saline solution. Once the diagnosis of Streptococcus p neumoniae meningitis was made, carbapenem and glycopeptide antibiotic therapy was started, in addition to glucocorticoid therapy (dexamethasone).

A right internal jugular central venous catheter was inserted after the diagnosis of meningitis was made.

Outcome and follow-up

The patient suffered a cardiac arrest on day 22 and died.

Discussion

Our patient was fit and well before the accident. He then developed new-onset meningitis, with marked increase in C-reactive protein and procalcitonin levels above baseline. WBC count elevations in early trauma are common, and fever is well described due to interleukin-6 production.¹ The elevated WBC at admission is a very non-specific sign in the trauma population. The level began to decline day 1 post admission, and there was an absence of fever.^{2 3}

The only reasonable explanation is that the pneumococcus gained access to the brain through fractures in either the frontal or sphenoid sinuses. This is supported by the evidence of intracranial air.

Despite two early CT scans being negative for features of raised intracranial pressure, brainstem death occurred, with latter evidence of hypoxic ischaemic changes on MRI. This strongly suggests that the mechanism of brain death in this patient was associated with the acquired meningeal pathology, rather than the primary brain injury.

The initial CT scan did not correlate with the low GCS. This can be explained by potential diffuse axonal injury.

It is possible that the patient progressed to a herniation syndrome within 2 hours of the CT on day 2 at time of deterioration. However, the fact that the ventricles were dilated, and that pus was discovered in said ventricles, suggests that the patient had developed non-communicating hydrocephalus secondary to overwhelming infection.

Pathophysiological evidence exists for microvascular thrombosis as a direct consequence of S. pneumoniae infection.⁴ It is likely that overwhelming sepsis caused profound microvascular injury with direct brain and brainstem hypoxic ischaemic injury.

Current practice in the management of base of skull fractures does not support the use of antibiotic prophylaxis. The most recent Cochrane review⁵ was conducted in 2015, and did not find evidence to support the use of prophylactic antibiotics for meningitis prophylaxis in these patients. This is supported by work in paediatric base of skull fractures. However, the methodological quality of the papers reviewed is very heterogeneous. Furthermore, little work has been done assessing whether the presence of intracranial air (which suggests ingress, rather than outward leak) contributes to the rate of infection.

Eftekhar and colleagues found that prophylactic ceftriaxone in the presence of traumatic pneumocephalus did not affect the incidence of meningitis. Significant methodological flaws existed, however. Patients were not assessed for the potential source of the air, and progressive pneumocephalus was not an independent variable.⁶

Pneumocephalus and meningitis have been reported as a consequence of acute otitis media and mastoiditis, establishing a precedent for ingress of S. pneumoniae from air-filled sinus.⁷ Sphenoid sinusitis may also be complicated by pneumococcal meningitis.⁸

The incidence of meningitis in patients with posttraumatic CSF leaks is 5%–10%.⁹ Pneumococcal meningitis is the most common form, in 83% of cases.¹⁰ The incidence of meningitis in patients with base of skull fracture but no CSF leak, is currently unknown.¹¹ Risk of meningitis is associated with CSF leaks, and the duration of leak.

It is estimated that 4% of adults carry S. pneumoniae, with asymptomatic colonisation of the nasopharynx. Carriage rates increase up to 40% for adults living in crowded condition.

To develop pneumococcal meningitis one needs (a) a host colonised with a strain of pneumococcus and no immunity, (b) a break in natural barriers (such as a base of skull fracture with CSF leak), or (c) a reduced immune state (any immunocompromised state, splenectomy).⁴

Recent literature discusses the importance of pneumococcal vaccine as prophylaxis against meningitis in basal skull fracture patients. In a retrospective study of 602 patients where 99 patients received ‘pneumovax’ and 503 did not, the results were not statistically significant but the authors suggest administering the vaccine in patients with severe head trauma.¹²

Another study compared early vaccination within 10 days after trauma to late vaccination after 3 weeks and found good response to vaccine with high antibody levels in both groups, with different serotypes. The authors believe that early vaccination is better, as neurotrauma is associated with decreased T-cell function. They recommend the T-cell-independent pneumococcal polysaccharide vaccine.¹³ Of note, our patient had not been vaccinated against S. pneumoniae.

Learning points.

• Rapid, fatal meningitis can develop in the setting of traumatic base of skull fracture, and a high index of suspicion should be maintained.

• Our case illustrates that the location of the fracture and associated features such as pneumocephalus may be additional risk factors which should prompt a different decision matrix, whether cerebrospinal fluid leak is present or not.

• Our recommendation to prevent mortality in patients with traumatic pneumocephalus is to assiduously search for the source of the air. Should the air arise from a sinus which may be colonised with bacteria, aggressive antibiotic prophylaxis with a centrally active agent may be warranted. However, more research is required before this can be advocated as routine practice. Figure 5 illustrates the proximity of the sinuses to the brain contents.

• Further research is needed as to the type of antibiotic prophylaxis (ceftriaxone may not be best¹⁴), and whether early vaccination in vaccine-naïve patients with traumatic head injury is required.

• Mechanism of cerebral injury with pneumococcal disease is currently unclear. Our patient developed brainstem death without evidence of markedly raised intracranial pressure nor transtentorial herniation on CT head at the time of brainstem death. Scattered case reports do exist¹⁵ ; our case also adds to the literature in terms of understanding the pathophysiological process involved in pneumococcal infections of the brain.