Neisseria meningitidis is a gram-negative diplococcus exclusively infecting humans. The acute systemic meningococcal disease manifests variously as meningitis, meningitis with meningococcemia, or meningococcemia without clinical evidence of meningitis.1,2

However, unlike in other bacterial meningitis, the focal neurologic signs and seizures are less common in meningococcal meningitis as correlated with postmortem findings.3,4 The reported neurological complications include cerebral infarction, cerebral herniation, hydrocephalus, cranial nerve palsies, and vascular complications.1,3,5−7

Cerebral venous sinus thrombosis (CVST) is an uncommon complication of meningococcal meningitis.1 In contrast, in pneumococcal meningitis the incidence of CVST was reported at 10.3%.6 We present the case of a 42-year-old man diagnosed with CVST associated with meningococcal meningitis and discuss the use of anticoagulant therapy.

Case report

A 42-year-old male, manual laborer with no significant past medical illness was admitted to the emergency department with a four-hour history of altered sensorium, generalized fatigue, headache, and an episode of urinary incontinence. There was no history of associated involuntary movements or symptoms associated with cranial nerve involvement. There was no reliable person available to give details of his past medical illness including the history in the run-up to his current presentation.

On examination, no skin rash was observed. He was stuporous with occasional spontaneous eye opening. He had neck stiffness and could localize to painful stimuli. No other lateralizing signs or papilledema were present on comprehensive neurological examination. The patient was intubated under sedation for respiratory protection. Blood work revealed an elevated white blood cell (WBC) count of 23.43 × 109/L (normal range = 4.00−11.00 × 109/L) with 88% neutrophils and thrombocytopenia with a platelet count of 53 × 109/L (normal range = 140−400 × 109/L). His random blood glucose level was 11.8 mmol/L (normal range = 2.8−8.8 mmol/L), and he had an elevated activated partial thromboplastin time (aPTT) of 41.3 s (normal range = 28.6−38.2 s), and elevated C-reactive protein (CRP) levels of 302.88 mg/L (normal range = 0−5 mg/L). Plain computed tomography (CT) [Figure 1] and CT venogram [Figure 2] were suggestive of straight sinus thrombosis. There were no subdural collections, hydrocephalus, or midline shift.

Empiric therapy with acyclovir, vancomycin, and ceftriaxone was started. Lumbar puncture showed findings suggestive of bacterial meningitis (WBC count of 7631 × 106/L (normal range = 0−5 × 106/L), red blood cell count of 4000 × 106/L, protein level of 5 968 mg/L (range = 150−450 mg/L), and glucose of 0.42 mmol/L (normal range = 2.22−3.89 mmol/L)). The culture of cerebrospinal fluid revealed gram-negative diplococcus, which was confirmed to be N. meningitidis (A/Y antigen by latex agglutination assay). Other blood work showed elevated levels of fibrinogen at 11.2 g/L (normal range = 1.9−4.3 g/L), D-dimer of 1.1 µg/mL (normal ≤ 0.5 µg/mL), blood creatinine levels of 171 µmol/L (normal range = 50−104 µmol/L), urea of 9.7 mmol/L (normal ≤ 8.3 mmol/L), and total and direct bilirubin levels of 22.3 µmol/L (normal ≤ 21 µmol/L) and 19.1 µmol/L (normal ≤ 5 µmol/L), respectively. Total protein and albumin were both decreased at 56 g/L (normal range = 64−83 g/L) and 25 g/L (normal range = 35−52 g/L), respectively.

On the third day, sedation was stopped, and he was extubated. His platelet counts improved to 163 000/µL on the fourth day of his admission. He complained about generalized pressure like headache, which was initially 7/10 severity and decreased to 2−3/10 over the first 10 days. He did not have any neck stiffness after extubation and the headache was treated symptomatically. Over the course of the following week, the patient’s condition continued to improve and ceftriaxone was given for 14 days. Except for a headache, the patient’s course was uneventful and he made a full recovery with improvement in his platelet levels to 202 × 109/L, WBC counts of 12.54 × 109, aPTT of 36 s, and CRP 86.3 mg/L at the end of his antibiotic regimen. At follow-up, one week after discharge, he did not have any symptoms or signs of neurological disease. He was subsequently lost to follow-up.

Discussion

Various infections of central nervous system (CNS) can cause different forms of cerebrovascular disease. In a study of 83 patients with meningitis, cerebrovascular complications were reported in 13 patients.8 The pathological processes involved are either para-infectious immune-mediated causing vasospasm or thrombosis, vasculitis affecting primarily the vessels at the base of the brain in meningitis, or a hypercoagulable state in combination with endothelial dysfunction
resulting from activation of inflammatory and procoagulant cascades.

CNS infections leading to CVST had a wide range of incidence as per literature review. In a multinational, multicenter study, CNS infections accounted for only 2.1% of the 624 patients with CVST.7 In a 2016 single-center prospective cohort study from India, the reported incidence was 19.8% of 87 cases.9 There are reports of cerebral venous thrombosis occurring in association with meningitides caused by Streptococcus pneumonia, Mycobacterium tuberculosis, coccidioidomycosis, and Fusobacterium necrophorum.8,10,11

Meningococcal infection of CNS causing CVST is uncommon.1,6 Disseminated intravascular coagulopathy and vascular thrombosis are known to occur in meningococcal infection due to the high levels of circulating procoagulant microparticles from platelets or granulocytes and disordered protein C activation in endothelial cells.3,12 Meningococcal infection causes increased vascular permeability associated with pathological vasoconstriction, vasodilation and intravascular thrombosis resulting in manifestations such as purpura fulminans to even infarction and gangrene of extremities. Involvement of plasminogen activator inhibitor-1 is suggested as a cause of the thrombotic events.13

The manifestations of invasive meningococcal disease are meningitis, septicemia, or a combination of both. It may also present as pneumonia, conjunctivitis, otitis media, epiglottitis, arthritis, urethritis and pericarditis, chronic meningococcemia, post-meningococcal reactive disease, and self-mutilating behavior.1,2 Headache is by far the most frequent presenting symptom in a patient with CVST.14,15 In a study of 59 patients with CVST, impaired consciousness was reported in 39% of patients.16 Similar findings were also described in a series of 111 patients with CVST where headache and altered sensorium were found to be the presenting feature in 69% and 27% of patients, respectively.15 This was also the case in our patient.

Beneficial effects of heparin in CVST have been reported even in patients with intracerebral hemorrhage. Current consensus guidelines including European Federation of Neurological Societies guidelines 2011, American Academy of Chest Physicians 2012, and American Heart Association/American Stroke Association 2014 support the use of anticoagulation for the acute treatment of CVST. The fifth edition 2016 National Institute for Health and Care Excellence guidelines for stroke recommends that patients with cerebral venous thrombosis (including those with secondary cerebral hemorrhage) should receive a full-dose of anticoagulation therapy (initially a full-dose heparin and then warfarin with a target international normalized ratio of 2–3) for at least three months unless there are comorbidities that preclude their use.

There is considerable debate regarding the use of anticoagulant therapy in the presence of meningococcal infection. Nürnberger et al,17 recommended the use of anticoagulant therapy with or without plasma substitution amongst pediatric patients with systemic meningococcal infection.However, controlled clinical trials with heparin as an adjunctive therapy in meningococcemia have not established its safety or usefulness.18,19 There are case reports wherein anticoagulant therapy was used in the management of CVST in the presence of meningococcal infection.5

Studies done to evaluate the prognosis of CVST showed impaired consciousness, coma, paresis, intracerebral hemorrhages, older age, focal neurological deficits, and septic CVST as poor prognostic factors.14,16,20 Evaluation of these prognostic factors may help in guiding the management of CVST in the presence of complicating conditions such as meningococcal infection on whether or not to adopt anticoagulant measures.

Conclusion

We presented a case of meningococcal meningitis with thrombosis of the straight sinus. The patient was managed with antibiotic therapy and made a complete recovery. The use of anticoagulation in CVST secondary to meningococcal infection needs further studies to establish its usefulness.

Disclosure

The authors declared no conflicts of interest.

references

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