Lemierre-like syndrome presenting with extensive intracranial and central venous thrombosis without pulmonary embolism: illustrative case

Abstract

BACKGROUND

Lemierre-like syndrome is a rare septic thrombotic disorder caused by non-Fusobacterium pathogens. Presentations with predominantly intracranial involvement and extensive central venous thrombosis are particularly uncommon, and optimal management remains unclear.

OBSERVATIONS

A 75-year-old female presented with impaired consciousness, fever, and right exophthalmos with conjunctival injection following mild sore throat. Contrast-enhanced CT demonstrated extensive thrombosis involving the superior vena cava, bilateral internal jugular veins, bilateral transverse-sigmoid sinuses, cavernous sinuses, and bilateral superior ophthalmic veins. There was no evidence of pulmonary embolism or septic pulmonary lesions. Brain MRI revealed right occipital venous infarction and marked cerebral venous congestion. Blood cultures yielded Streptococcus intermedius. Intravenous antimicrobial therapy and systemic anticoagulation were initiated immediately. Because antithrombin (AT) activity progressively decreased during the acute phase, adjunctive AT supplementation was administered. Serial MR venography demonstrated gradual recanalization, and the patient achieved favorable neurological recovery without hemorrhagic complications.

LESSONS

Early recognition of Lemierre-like syndrome with predominant intracranial involvement and individualized multidisciplinary management may contribute to favorable neurological outcomes.

https://thejns.org/doi/10.3171/CASE26541

Lemierre syndrome is a rare septic thrombophlebitis of the internal jugular vein (IJV) following oropharyngeal infection, classically associated with Fusobacterium necrophorum and septic pulmonary embolism (PE).^1–3 Although regarded as an infectious disease, intracranial extension of thrombosis may occur and result in serious neurovascular complications including cerebral venous congestion, venous infarction, and neuro-ophthalmological manifestations.^4,5

Similar clinicoradiological presentations caused by non-­Fusobacterium pathogens have been increasingly described and are often referred to as Lemierre-like syndrome, although no formal diagnostic criteria have been established.⁶ Management of extensive intracranial venous thrombosis in Lemierre-like syndrome remains controversial, particularly regarding anticoagulation and adjunctive antithrombotic strategies.⁷

We report a case of Streptococcus intermedius–associated Lemierre-like syndrome presenting with extensive intracranial and central venous thrombosis causing cerebral venous infarction and marked intracranial venous congestion without PE. This case represents an unusual neurovascular presentation of Lemierre-like syndrome and individualized management including aggressive anticoagulation and adjunctive antithrombotic therapy.

Illustrative Case

A 75-year-old woman with no medical history presented to the emergency department with impaired consciousness and fever. She had experienced mild right-sided sore throat for 1 week and had developed dizziness and poor oral intake several days before admission. On arrival, her Glasgow Coma Scale score was E3V4M6. Neurological examination revealed somnolence without focal motor deficits, visual field defects, ophthalmoplegia, papilledema, or signs of intracranial hypertension. However, marked right-sided exophthalmos and conjunctival injection were present, suggesting orbital venous congestion. Laboratory testing demonstrated marked leukocytosis (white blood cell count 28,700/μL) with neutrophil predominance (93%), mild thrombocytopenia (126 × 10³/μL), hypoalbuminemia (2.1 g/dL), elevated C-reactive protein (29.9 mg/dL), and fibrin/fibrinogen degradation products (21.8 μg/mL) with increased D-dimer (17.8 μg/mL) and antithrombin (AT) activity of 80%, suggesting sepsis-associated coagulopathy without overt disseminated intravascular coagulation (DIC) (Table 1).

TABLE 1.

Laboratory data on admission

Parameter	Recorded Value	Reference Range
Hematological findings
White blood cell count, /μL	28,700	3300–8600
Neutrophil fraction, %	93	40–65
Lymphocyte fraction, %	2.0	20–45
Hemoglobin, g/dL	14.9	11.6–14.8
Platelet count, /μL	126 × 103	158–348 × 103
Biochemical findings
Total protein, g/dL	5.9	6.6–8.1
Albumin, g/dL	2.1	4.1–5.1
Total bilirubin, mg/dL	0.82	0.4–1.5
Aspartate aminotransferase, U/L	57	13–30
Alanine aminotransferase, U/L	56	7.0–23
Gamma-glutamyl transpeptidase, U/L	67	9.0–32
Lactate dehydrogenase, U/L	394	124–222
Creatine kinase, U/L	199	41–153
Blood urea nitrogen, mg/dL	66.7	8.0–20
Creatinine, mg/dL	0.91	0.46–0.79
Sodium, mmol/L	142	138–145
Potassium, mmol/L	3.6	3.6–4.8
C-reactive protein, mg/dL	29.9	0.0–0.14
Coagulation findings
Prothrombin time–international normalized ratio	1.02
Activated partial thromboplastin time, sec	25.1	24.0–34.0
D-dimer, μg/mL	17.8	≤1.0
Fibrinogen, mg/dL	598	185–400
Fibrin/fibrinogen degradation products, µg/mL	21.8	≤5.0
AT III activity, %	80	80–130

Contrast-enhanced chest CT demonstrated no evidence of PE or septic pulmonary lesions (Fig. 1A and B). Head CT demonstrated neither acute intracranial hemorrhage nor mass lesion. Contrast-enhanced CT revealed extensive venous thrombosis involving the superior vena cava (SVC) (Fig. 1C), bilateral IJVs (predominantly on the right) (Fig. 1D), bilateral sigmoid sinuses (SSs) (Fig. 1E), bilateral transverse sinuses (TSs) (Fig. 1F), bilateral cavernous sinuses (CSs), and superior ophthalmic veins (SOVs) (Fig. 1G). Right tonsillar enlargement and tonsillolithiasis were noted without abscess formation adjacent to the right IJV thrombosis (Fig. 1H). Echocardiography showed no evidence of infective endocarditis. Diffusion-weighted MRI demonstrated acute infarction in the right occipital lobe (Fig. 2A). Susceptibility-weighted imaging (SWI) revealed corresponding hypointense signals suggestive of venous congestion (Fig. 2B). MR venography (MRV) demonstrated markedly impaired cerebral venous outflow with only limited residual patency through the left TS-SS-IJV pathway (Fig. 2C).

FIG. 1.

Chest CT and contrast-enhanced CT scans obtained on admission. A: Coronal chest CT scan showing no pulmonary nodules, cavitary lesions, or other findings suggestive of septic pulmonary emboli. B: Axial contrast-enhanced CT scan obtained at the level of the pulmonary artery bifurcation demonstrating no evidence of PE. C–F:Coronal contrast-enhanced CT scans demonstrating thrombosis extending from the SVC to the right IJV (C), bilateral high cervical IJV thrombosis predominantly on the right side (D), bilateral SS thrombosis (E), and bilateral TS thrombosis (F). G and H:Axial contrast-enhanced CT scans demonstrating bilateral CS and SOV thrombosis with venous dilatation associated with orbital venous congestion (G), as well as right tonsillar enlargement and tonsillolithiasis (open triangle) adjacent to the right IJV thrombosis (H). Arrows indicate representative thrombosed venous structures on the right side. R = right.

FIG. 2.

MR images and venograms obtained on admission. A:Diffusion-weighted image showing acute infarction in the right occipital lobe (arrow). B: Susceptibility-weighted image showing prominent hypointense cortical venous signals suggestive of venous congestion (arrowhead). C: MR venogram revealing markedly impaired cerebral venous outflow with only limited residual patency through the left TS-SS-IJV pathway (arrows).

Based on these findings, Lemierre-like syndrome with extensive intracranial thrombosis was diagnosed. Additional coagulation studies demonstrated no apparent underlying thrombophilic abnormalities. After blood cultures were obtained, intravenous meropenem (3.0 g daily) was initiated. Consultation with the otolaryngology team confirmed the absence of a drainable peritonsillar abscess; therefore, surgical drainage was not performed. Given the presence of extensive intracranial venous thrombosis with venous infarction, systemic anticoagulation with intravenous heparin was initiated immediately, targeting an activated partial thromboplastin time of 1.5–2.0 times the normal level. Endovascular thrombectomy (EVT) was deferred because the patient had no progressive neurological deficits, visual impairment, papilledema, or other evidence of malignant intracranial venous hypertension.

On hospital day 2, blood cultures became positive for ­gram-positive cocci, prompting the addition of vancomycin therapy with therapeutic drug monitoring. AT activity subsequently decreased from 80% to 67% despite anticoagulation. Although the patient did not meet overt DIC criteria, progressive sepsis-associated coagulopathy was suspected, and adjunctive AT supplementation was administered for 3 days to support endogenous anticoagulant activity. The patient became afebrile following treatment, and inflammatory markers gradually improved. Follow-up MRV on hospital day 8 demonstrated recanalization of the left TS-SS-IJV pathway (Fig. 3A). SWI showed a reduction of prominent hypointense cortical venous signals in the right occipital lobe, suggesting improvement of venous congestion (Fig. 3B). Her consciousness returned to normal, and the exophthalmos and conjunctival injection resolved completely. No hemorrhagic complications occurred during anticoagulation therapy. Blood cultures ultimately yielded S. intermedius, and antimicrobial therapy was de-escalated to sulbactam/ampicillin (6 g daily) on hospital day 14. Oral warfarin was initiated on hospital day 15, and intravenous heparin was discontinued on hospital day 21. Intravenous antimicrobial therapy was completed on hospital day 30. The patient was transferred to a rehabilitation hospital on hospital day 41 with a modified Rankin Scale score of 1. The clinical course during hospitalization is summarized in Fig. 4. Follow-up MRV obtained 18 months after treatment demonstrated sustained venous patency without recurrent thrombosis.

FIG. 3.

Follow-up MR image and venogram obtained after treatment. A:MR venogram showing recanalization of the left TS-SS-IJV pathway and improvement of cerebral venous outflow (arrows). B: Axial susceptibility-weighted image showing reduction of prominent hypointense cortical venous signals in the right occipital lobe, suggesting improvement of venous congestion (arrowhead).

FIG. 4.

Clinical course during hospitalization showing serial changes in inflammatory and coagulation markers together with antimicrobial therapy, anticoagulation therapy, and adjunctive AT supplementation. ABPC/SBT = ampicillin/sulbactam; CRP = C-reactive protein; MEPM = meropenem; VCM = vancomycin.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

The present case illustrates an atypical Lemierre-like syndrome caused by S. intermedius, presenting with extensive intracranial and central venous thrombosis without PE. Despite only mild tonsillar inflammation without abscess formation, the patient developed widespread thrombosis involving the bilateral TSs, SSs, CSs, SOVs, IJVs, and SVC, resulting in severe intracranial outflow impairment, orbital venous congestion, and cerebral venous infarction. Aggressive medical management including antimicrobial therapy, systemic anticoagulation, and adjunctive AT supplementation led to progressive recanalization and favorable neurological recovery without EVT.

Unlike classical Lemierre syndrome, which is most commonly caused by F. necrophorum and characterized by septic PE, ­Lemierre-like syndrome appears to encompass a broader and more heterogeneous clinicoradiological spectrum.^8,9 Reported causative organisms include various streptococcal species, Staphylococcus aureus, and other aerobic bacteria, often accompanied by atypical thrombotic distributions and metastatic infectious complications.^10,11 Although PE remains the most common manifestation, intracranial complications such as cerebral venous sinus thrombosis (CVST), orbital venous congestion, and cerebral venous infarction have also been reported.^7,10 These observations suggest that Lemierre-like syndrome may represent a heterogeneous septic thrombotic disorder with variable routes of venous propagation and organ involvement rather than a single uniform disease entity. The present case was considered Lemierre-like syndrome rather than sepsis-associated CVST because characteristic clinicoradiological features were present, including antecedent oropharyngeal infection, contiguous IJV thrombosis, S. ­intermedius bacteremia, and extensive cervicocranial venous propagation.

PE is one of the hallmark manifestations of classical Lemierre syndrome and is reported in the majority of cases.¹ In addition to PE, septic embolic dissemination to the joints, liver, bone, and soft tissues has also been described, reflecting the systemic metastatic nature of Lemierre syndrome.^2,3 In the typical disease course, septic thrombophlebitis originating in the IJV propagates through the systemic venous circulation and results in embolic dissemination to the pulmonary vasculature.³ In the present case, chest CT demonstrated no evidence of PE or septic pulmonary lesions despite the extensive thrombotic burden. Instead, thrombosis predominantly involved the CSs, TSs, SSs, SOVs, and central venous system, resulting in severe intracranial outflow impairment. Such extensive intracranial venous involvement with orbital venous congestion may mimic other neurovascular emergencies, particularly carotid-cavernous fistula, and should therefore be recognized in the differential diagnosis of unusual CVST presentations. The radiographic distribution of thrombosis in the present case suggests retrograde contiguous propagation through the cervicocranial venous network rather than isolated thrombosis originating solely within the IJV. The close anatomical relationship between the inflamed tonsillar region and adjacent IJV thrombosis suggested that septic thrombosis may have initially developed in peripharyngeal venous tributaries surrounding the infectious focus.^12,13 Extensive septic thrombosis associated with elevated venous pressure may have facilitated retrograde contiguous propagation through the cervicocranial venous system despite the presence of IJV valves.

Although anticoagulation for Lemierre and Lemierre-like syndrome remains controversial because of the lack of high-level evidence, systemic anticoagulation is frequently considered in patients with extensive thrombosis, cerebral venous sinus involvement, or thrombotic progression despite antimicrobial therapy.^14,15 Similarly, the role of AT supplementation in Lemierre-like syndrome has not been established. International sepsis guidelines do not recommend routine AT administration because of insufficient evidence for survival benefit in sepsis-associated coagulopathy.¹⁶ However, marked reductions in endogenous AT activity have been associated with severe septic coagulopathy with extensive thrombosis.^17,18 In the present case, AT activity progressively decreased despite anticoagulation, whereas overt DIC criteria were not fulfilled. Therefore, AT supplementation was used as adjunctive therapy in the setting of evolving sepsis-associated coagulopathy rather than established DIC. Because anticoagulation, antimicrobial therapy, and AT supplementation were initiated during the same treatment period, a causal relationship between AT supplementation and recanalization cannot be established.

EVT for CVST is generally reserved for patients with neurological deterioration, impending herniation, or failure of medical management.¹⁹ In the present case, aggressive systemic anticoagulation was initiated because of extensive intracranial venous thrombosis associated with cerebral venous infarction and severe intracranial outflow impairment. However, EVT was deferred because the patient exhibited no progressive focal neurological deficits, visual deterioration, papilledema, or clinical evidence of malignant intracranial venous hypertension, and serial imaging demonstrated early recanalization following medical therapy.

Lemierre-like syndrome with predominant intracranial involvement should be recognized as a multidisciplinary disease involving otolaryngology, neurology, neurosurgery, emergency medicine, and infectious diseases.⁵ Extensive intracranial venous thrombosis and orbital venous congestion may develop even in the absence of severe pharyngeal findings or PE.^1–3,7 Early multidisciplinary collaboration is important for accurate diagnosis, timely neurovascular evaluation, and individualized management before irreversible cerebral venous infarction or malignant intracranial venous hypertension develops.

Lessons

Lemierre-like syndrome with predominant intracranial involvement may occur even in the absence of PE or severe pharyngeal infection. Extensive septic thrombosis can propagate retrogradely through the cervicocranial venous system and result in severe neurovascular complications. Early recognition and multidisciplinary management are important for favorable outcomes.

Acknowledgments

Funding is acknowledged from the Sanikai Foundation (to H.N.).

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Nakajima. Acquisition of data: Nakajima. Analysis and interpretation of data: Nakajima, Suzuki. Drafting the article: Nakajima, Yago. Critically revising the article: Nakajima, Tsuda, Suzuki. Reviewed submitted version of manuscript: Nakajima, Tsuda, Suzuki. Approved the final version of the manuscript on behalf of all authors: Nakajima. Administrative/technical/material support: Sato. Study supervision: Suzuki.

Correspondence

Hideki Nakajima: Matsusaka Chuo General Hospital, Matsusaka, Mie, Japan. zima0131@gmail.com.