- Top of page
- What this paper adds
- Case Report
Lemierre syndrome is a distinct clinical syndrome comprising oropharyngeal sepsis and fever, internal jugular vein thrombosis and remote septic metastases caused by Fusobacterium species. The mortality rate was historically high and although use of antibiotics led to a dramatic fall in incidence, a resurgence has been seen recently. A 14-year-old male developed Lemierre syndrome after tonsillitis. There was extensive leptomeningitis, especially over the clivus, causing 6th and 12th cranial nerve palsies, a clinical feature termed the ‘clival syndrome’. He also developed an epidural abscess in the cervical spine, which was unsafe for surgical drainage. Conservative treatment with an extended course of antibiotics and anticoagulation for jugular vein thrombosis led to a good recovery. A 15-year-old female developed Lemierre syndrome after a persistent sore throat lasting 7 weeks. She had palsy of the 12th cranial nerve from clival osteomyelitis. She was treated with a 6-week course of antibiotics and anticoagulants leading to almost full recovery at 3-month review. Awareness of the potential neurological complications of Lemierre syndrome and prompt management are crucial in reducing morbidity and mortality in this ‘forgotten disease’.
Lemierre syndrome is caused by Fusobacterium species and was first described almost 75 years ago by Lemierre.1 It is characterized by oropharyngeal infection, thrombosis of the internal jugular vein, and multiple septic metastases. Oropharyngitis associated with fever and chills is the first sign of the illness, which later evolves into metastatic sepsis involving other organs. This pattern is so characteristic as to form a unique clinical syndrome such that, according to Lemierre1 in diagnosing the disease, ‘mistake is almost impossible’. Lemierre syndrome commonly affects adolescents and in the pre-antibiotic era it carried a high mortality rate. With the advent of antibiotics the incidence declined; however, a marked resurgence has been seen recently2,3 and the disease still carries significant rates of morbidity and mortality, mainly because of the virulence of the organism and partly because of lack of awareness of the condition. Here we discuss two cases of Lemierre syndrome with neurological features. The authors have obtained consent for publication of these case reports from the parents of the persons described.
- Top of page
- What this paper adds
- Case Report
Lemierre syndrome historically had a high mortality rate, up to 90% before the advent of antibiotics.1 Its incidence gradually declined, leading it to be called the ‘forgotten disease’. The Anaerobe Reference Laboratory for England and Wales, however, recorded a sharp rise in the number of Fusobacterium isolates in the late 1990s,4 (9 isolates in 1991 increasing to 37 in 1999, with an annual average of 19 during that decade) which coincided with the fall in antibiotic prescriptions for upper respiratory tract infections in England and Wales.5
Fusobacterium necrophorum is an obligate anaerobic Gram-negative bacillus that is part of the human throat and gastrointestinal flora.6 The oropharynx is often the primary focus of infection, but occasionally Lemierre syndrome follows otitis, mastoiditis, dental abscess, etc.2,6,7 Virulent strains induce platelet aggregation mediated by a lipopolysaccharide endotoxin8 resulting in internal jugular vein thrombosis, either through contiguous or haematogenous spread. Multiplication of the organism occurs within the thrombus, which fragments into septic emboli. This results in protean clinical manifestations, often distracting clinicians from the primary symptoms, which have by then resolved or improved.6 Diagnostic delay ensues, as was evident in case 1 whereby renal failure was mistaken to be the foremost problem.
The clinical features relate to metastatic infections in distant organs, the most common being the lungs.6 Osteomyelitis, septic arthritis, liver involvement, acute renal failure, endocarditis and endophthalmitis9 have also been reported. Meningitis, although a rare feature, can be quite severe, with complications such as cortical infarction, brain abscess and cranial nerve involvement.2,7
Combined involvement of 6th and 12th cranial nerves is unusual and is a known feature of the so-called ‘clival syndrome’, wherein the 6th to 12th cranial nerves are affected by various lesions as they pass along the clival margin. This entity was originally described by Godtfredsen10 in 1947 in patients with nasopharyngeal carcinoma. Keane11 described clival lesions in 18 of 21 adult patients with multiple nerve palsies involving the 6th to 12th cranial nerves: the most common cause was malignancy, with meningitis and osteomyelitis in one case each. In five of these patients, the palsy was limited to the 6th and 12th nerves. A clival pattern of neuropathy has not been reported so far in Lemierre syndrome, and lack of awareness of this possibility can lead to diagnostic uncertainty. Leptomeningitis in the clival region contributed to the combined 6th and 12th nerve palsy in case 1. In case 2, clival osteomyelitis led to isolated palsy of the 12th nerve. Thickened meningitis with multiple cranial neuropathies should also raise the possibility of chronic granulomatous meningitis12 and investigations to exclude potential underlying causes such as tuberculosis, fungal infections and inflammatory disorders should be undertaken.
Spinal epidural abscess is a rare complication of Lemierre syndrome, with one previous report in an adult.13 Although Lemierre syndrome is more common in adolescents, to our knowledge, this complication has not been reported before in a child.
Owing to the wide variation in the diagnostic criteria used in published case series, Riordan6 proposed the following: a history of orophrayngeal illness in the preceding 4 weeks, metastasis in a remote site, and internal jugular vein thrombophlebitis or isolation of Fusobacterium species on blood culture. In case 2, blood culture was only collected 7 weeks into the illness and after several courses of oral antibiotics, making isolation of Fusobacterium necrophorum difficult. Although Epstein-Barr virus was isolated, this is unlikely to produce the described lesions on its own. Moreover, Epstein-Barr virus and haemolytic streptococci are often found as concomitant infections preceding the onset of Lemierre syndrome.6,14
The published literature suggests that most cases of Lemierre syndrome are amenable to antimicrobial therapy. Choice of antibiotics must be based on in vitro data and generally include either penicillin in combination with metronidazole or monotherapy with clindamycin.4,6,14,15 Quite uniquely, response is slow, taking approximately 8 to 12 days for resolution of fever.15 The consensus opinion seems to favour treatment for a total of 6 weeks, with about 2 to 3 weeks of intravenous therapy because of the possibility of relapse.14,15
There is no firm evidence for the role of anticoagulation in internal jugular vein thrombosis. Resolution of thrombosis in the internal jugular vein is no different in patients who did not receive anticoagulation than in those who did.6,14–17 However, in cases involving dural venous sinuses, because there is a potential for cerebral venous infarcts, especially in children, anticoagulation is generally advocated.15
Surgical drainage of abscesses such as empyema, septic arthritis, and intracranial collections is a key part of management to ensure optimal and rapid resolution.6,14 Involvement of vulnerable anatomical sites, such as seen in case 1, may, however, preclude surgical intervention.