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n engl j med 371;21 nejm.org November 20, 20142018 n engl j med 371;21 nejm.org November 20, 20142018

Pr esen tation of C a se

Dr. Nicholas A. Morris (Neurology): An 18-year-old woman was admitted to this hos-pital because of fever, pharyngitis, facial swelling, and diplopia.

The patient had been well until 2 weeks before the current admission, when a headache and sore throat developed, without a fever. On evaluation at her physi-cians office, a rapid test for streptococcal pharyngitis was negative, and she re-turned home. During the next 2 days, throat pain persisted and oral intake de-creased. She was admitted to the observation unit of another hospital because of dehydration, weakness, and fevers, with a temperature as high as 39.4C. A chest radiograph was normal.

The patient reportedly had a white-cell count of less than 2000 per cubic mil-limeter, positive tests for IgG and IgM antibodies to EpsteinBarr virus (EBV)spe-cific viral capsid antigen and antibodies to EBV nuclear antigen, and negative tests for heterophile antibodies, influenza A and B viruses, and IgM and IgG antibodies to cytomegalovirus (CMV). A pharyngeal culture grew group C streptococcus. Cultures of the blood and urine were sterile. A diagnosis of infectious mononucle-osis with possible bacterial superinfection was made. Intravenous fluids were ad-ministered, and her condition improved. On day 2, treatment with erythromycin was begun and she was discharged home.

Nine days before the current admission, trismus, pain on opening the mouth, and swelling on the right side of the face and jaw developed. The patient returned to the emergency department of the same hospital; parotitis was diagnosed, and ibuprofen was administered. Pain persisted on the right side of the jaw and was associated with temperatures as high as 38.3C and swelling and erythema of the right parotid gland and face.

Six days before the current admission, the patient was seen at a second hospital; prednisone and narcotic analgesic agents were administered, and massage of the parotid gland was performed. She returned home. Fevers persisted, and edema of the right lateral side of the face and neck worsened. Three days later, she was seen by her physician and was admitted to the second hospital. Computed tomography (CT) of the head and neck reportedly revealed no evidence of retropharyngeal or periton-

From the Departments of Medicine (K.R.O.), Pediatrics (K.R.O.), Radiology (J.M.J.), and Pathology (J.A.B.) and the Center for Global Health (K.R.O.), Massachusetts General Hospital; the Departments of Medicine (K.R.O.), Pediatrics (K.R.O.), Radiology (J.M.J.), and Pathology (J.A.B.), Harvard Medical School; and the Department of Ophthalmology (S.K.F.), Massachusetts Eye and Ear Infirmary all in Boston.

N Engl J Med 2014;371:2018-27.DOI: 10.1056/NEJMcpc1310001Copyright 2014 Massachusetts Medical Society.

Founded by Richard C. Cabot Eric S. Rosenberg, M.D., Editor Nancy Lee Harris, M.D., Editor JoAnne O. Shepard, M.D., Associate Editor Alice M. Cort, M.D., Associate Editor Sally H. Ebeling, Assistant Editor Emily K. McDonald, Assistant Editor

Case 36-2014: An 18-Year-Old Woman with Fever, Pharyngitis, and Double Vision

Kristian R. Olson, M.D., M.P.H., Suzanne K. Freitag, M.D., Jason M. Johnson, M.D., and John A. Branda, M.D.

Case Records of the Massachusetts General Hospital

The New England Journal of Medicine Downloaded from nejm.org on January 27, 2015. For personal use only. No other uses without permission.

Copyright 2014 Massachusetts Medical Society. All rights reserved.

n engl j med 371;21 nejm.org November 20, 2014 2019

Case Records of the Massachusetts Gener al Hospital

sillar abscesses. Trimethoprimsulfamethoxazole, clindamycin, and intravenous fluids were ad-ministered.

Two days before the current admission, swell-ing of the right eyelids and horizontal diplopia developed. On evaluation, there was decreased abduction of the right eye. Imaging studies were obtained.

Dr. Jason M. Johnson: Magnetic resonance imag-ing (MRI) of the head and neck, performed with and without the administration of contrast ma-terial, revealed a multiloculated, rim-enhancing fluid collection in the right parotid gland and inflammation of the masticator space. There was linear enhancement of the pachymeninges in the right temporal region, a finding that raised con-cern about meningitis. Diffusion-weighted im-ages obtained at the level of the parotid gland showed findings consistent with an abscess. There was an irregularity of the right cavernous sinus, without definite thrombosis. A subperios-teal abscess in the right orbit was also identified.

Dr. Morris: The patient was transferred to a third hospital. On examination, she was alert and communicative. The vital signs and oxygen satu-ration were normal. There was diffuse swelling of the right preauricular and periorbital areas, mild trismus, bilateral cervical submental and submandibular lymphadenopathy (greater on the right side than on the left), and preauricular and postauricular lymphadenopathy on the right side. White plaque was seen on the gingivobuccal sul-cus and anterior tongue, which was painful when scraped. The right Stensens duct was tender on firm compression, with no fluid discharge. On neurologic examination, the right eye had medial deviation, with an inability to abduct past the mid-line. The patient had mild difficulty with tan-dem walking. The general and neurologic ex-aminations were otherwise normal. The activated partial-thromboplastin time, red-cell indexes, and results of renal-function tests were normal, as were levels of electrolytes, magnesium, globulin, angiotensin-converting enzyme, and IgG, IgA, and IgM. Tests for heterophile antibodies, antibodies to human immunodeficiency virus (HIV) types 1 and 2, and HIV nucleic acid were negative; other test results are shown in Table 1. Urinalysis re-vealed trace protein, 3+ glucose, and 2+ urobi-linogen, along with squamous epithelial cells and bacteria, findings suggestive of contamination.

Dr. Johnson: MRI of the head, orbits, face, and

neck, performed with and without the adminis-tration of contrast material (Fig. 1), reportedly revealed changes consistent with multiple lobu-lated abscesses in the right parotid gland, with extensive inflammation surrounding the gland that involved the muscles of mastication, as well as a small subperiosteal abscess along the right lateral orbital wall, dural enhancement along the right temporal lobe, and enhancement along the cavernous sinus; these findings were again not thought to constitute definite evidence of throm-bosis. Changes consistent with extensive peri-odontal disease were also seen. Vancomycin, meropenem, and clindamycin were administered. Ultrasound-guided percutaneous fine-needle as-piration of fluid collected in the parotid gland was performed, and the aspirate was cultured. The following day, CT of the sinuses, performed with the administration of contrast material, re-portedly revealed preseptal swelling of the right eye extending to the temporal fossa, subperios-

VariableReference Range,

AdultsOn Admission to

Third Hospital

Hematocrit (%) 3648 28.0

Hemoglobin (g/dl) 11.516.4 9.8

Whitecell count (per mm3) 400010,000 8290

Differential count (%)

Neutrophils 4876 80.6

Lymphocytes 1841 11.3

Monocytes 4.011.0 7.7

Basophils 01.5 0.4

Platelet count (per mm3) 150,000450,000 119,000

Prothrombin time (sec) 12.214.6 15.8

Prothrombintime international normalized ratio

0.91.1 1.2

Glucose (mg/dl) 70100 173

Glycated hemoglobin (%) 4.25.8 5.9

Total protein (g/dl) 6.48.3 5.9

Albumin (g/dl) 3.55.2 2.3

Calcium (mg/dl) 8.810.7 7.9

Phosphorus (mg/dl) 2.44.3 3.3

* To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for calcium to millimoles per liter, multiply by 0.250. To convert the values for phosphorus to millimoles per liter, multiply by 0.3229.

Reference values are affected by many variables, including the patient population and the laboratory methods used. The reference ranges are those used at the third hospital.

Table 1. Laboratory Data.*



n engl j med 371;21 nejm.org November 20, 20142020

T h e n e w e ngl a nd j o u r na l o f m e dic i n e

teal enhancement adjacent to the right lateral rectus muscle, and heterogeneous enhancement and enlargement of the right parotid gland; there was no substantial improvement in the appear-ance of the orbital or parotid abnormalities as compared with the previous imaging studies.

Dr. Morris: The patient was transferred to Mas-sachusetts Eye and Ear Infirmary, which is af-filiated with this hospital. Medications on transfer included vancomycin, meropenem, clindamycin, trimethoprimsulfamethoxazole, and enoxaparin, as well as an albuterol inhaler, lorazepam, oxy-

codone, ibuprofen, and acetaminophen, as need-ed. She reported having fatigue and double vision, without headache, pain in her eye or throat, or pain with eye movements. She had a history of dysmenorrhea, for which she took norethindrone acetate and ethinyl estradiol oral contraceptives, and asthma. She was allergic to penicillins, which had caused urticaria, and was possibly allergic to cephalosporins. She lived with her family and attended high school. She did not smoke, drink alcohol, or use illicit drugs, and she had had no travel-related exposures.

Figure 1. MRI Scans of the Head and Neck.

T1weighted images of the head and neck were obtained after the administration of contrast material. A coronal image of the head shows temporal pachymeningeal enhancement and subtle leptomeningeal enhancement, findings suggestive of basilar and temporal meningitis (Panel A, arrows). A coronal fatsaturated image (Panel B) and an axial diffusionweighted image (Panel C) show changes consistent with abscess formation in the right parotid gland (arrows). Axial and coronal fatsaturated images (Panels D and E, respectively) show changes consistent with a subperiosteal abscess in the right orbit (arrows).

A B C

ED





On examination, the patient was somnolent but arousable. The vital signs were normal, as was the oxygen saturation while she was breath-ing ambient air. The right parotid gland, face, and neck were swollen, with marked periorbital edema of the right eyelid, minimal erythema and tenderness, and no palpable fluctuance; the right eye had 1+ lateral clear chemosis (Fig. 2). The right parotid gland was tender. There was a whitish plaque on the inner aspect of the right buccal mucosa, which was tender and had no obvious abscesses. The patient was able to swal-low oral secretions. A systolic murmur, grade 1 out of 6, was heard at the left lower sternal border. There was bilateral submandibular lymphade-nopathy, greater on the right side than on the left. On neurologic examination, visual acuity was 20/30 in the right eye and 20/20 in the left. In the right eye, supraduction was limited by 50%, abduction was slightly limited, and infraduction and adduction were normal; the left eye had normal motility, with splinting on upgaze. Other cranial-nerve functions (excluding smell, which was not tested) and the remainder of the general and neurologic examinations were normal.

Diagnostic procedures were performed, and the patient was admitted to this hospital.

Differ en ti a l Di agnosis

Dr. Kristian R. Olson: This patient is a previously healthy 18-year-old woman whose illness began with a sore throat and progressed to include fe-ver, facial swelling, and a deficit on abduction of the right eye. Fourteen days before this admis-sion, the patient had a sore throat and headache; at this time, her presentation was consistent with acute pharyngitis, a diagnosis that accounts for 6% of all outpatient visits in the United States.1

Pharyngitis

Over the ensuing 2 days, a high temperature de-veloped, throat pain persisted, and oral intake decreased, resulting in the patients first hospi-talization. My differential diagnosis at this point includes infectious pharyngitis, which can be caused by such viruses as rhinovirus, coxsackie-virus, and adenovirus. Mononucleosis-like illness-es, including EBV, CMV, and acute HIV infections, should be considered together, because it is not possible to distinguish among these infections clinically.2 Although testing for heterophile anti-

bodies was negative, only 25% of patients with EBV infection have detectable heterophile antibod-ies in the first week, and 10% never have these antibodies.3 This patients EBV-specific antibody profile provides evidence of recent EBV infection; however, the fulminant nature of her illness is not consistent with this diagnosis alone. Serologic testing for CMV was negative. Testing for HIV antibodies and HIV RNA (viral load) was negative, and there was no history of sexual activity or other risk factors that would raise concern about acute HIV infection.

An initial throat culture grew group C strep-tococcus; infection with this organism can be clinically indistinguishable from group A strep-tococcal infection.4 I suspect that this is un-

Figure 2. Photographs of the Patients Eye.

On presentation to the Massachusetts Eye and Ear Infirmary, the patient had periorbital erythema and edema surrounding the right eye (Panel A) and conjunctival injection and chemosis (Panel B). Photographs are courtesy of Dr. John B. Miller.

A

B





likely to be the sole cause of this patients ill-ness, because her condition worsened despite treatment with erythromycin. That she was suf-ficiently dehydrated to warrant admission may be an early indication that her condition is more serious than a typical pharyngitis.

Swelling of the Parotid Gland

During the 6-day period between the patients first and second hospital evaluations, swelling of her face and trismus developed, and the fevers persisted. She sought medical attention twice and was treated with ibuprofen, systemic gluco-corticoids, and narcotics before being again ad-mitted to the hospital. During this period, there were several potential clues; perhaps the most important was the development of swelling of the parotid gland. A number of noninfectious causes may result in enlargement of the parotid gland, including Sjgrens syndrome, which may be manifested unilaterally but is not usually as-sociated with pain or fevers. Heerfordts syn-drome is a variant of sarcoidosis that is mani-fested by fevers and occasionally by facial-nerve palsy; however, only a minority of patients pres-ent with painful swelling of the parotid gland, and it is usually bilateral. Mumps is a cause of infectious parotitis that has frequently been overlooked since the introduction of the vaccine in 1967. Mumps causes unilateral swelling of the parotid gland in 10% of cases and has resulted in several outbreaks in North America, including an outbreak involving teenagers who had re-ceived two doses of the vaccine.5 However, mumps typically resolves within 10 days in the absence of treatment, which is not consistent with the clinical deterioration seen in this case.

Does this patient have a peritonsillar or retro-pharyngeal abscess or Ludwigs angina? There are no typical findings, such as a change in vo-cal quality, difficulty swallowing, or persistent oropharyngeal pain, and CT did not reveal evi-dence of these conditions. Therefore, these are unlikely causes of the patients illness.

Given the patients pharyngitis, edema of the right side of the face, and persistent fevers, I must consider the diagnosis of Lemierres syndrome (i.e., the constellation of symptoms and signs that arise in the weeks following a painful throat infection). Diagnostic criteria include a history of anginal illness of the oropharynx within the preceding 4 weeks, evidence of metastatic le-

sions in the lungs or another remote site, and evidence of internal-jugular-vein thrombophlebi-tis or isolation of Fusobacterium necrophorum from the blood or another sterile site.6

Does this patients illness meet the criteria for Lemierres syndrome? A second MRI study shows inflammation of the muscles of mastica-tion and lobulated abscesses in the parotid gland, as well as a subperiostial abscess in the right orbit indicating metastatic infection. The facial swelling and chemosis could be caused by throm-bophlebitis in the carotid sheath and nearby vasculature. Inflammation in the periorbital struc-tures, parotid gland, and adjacent structures can result from extension of an infectious or inflam-matory process of the lateral pharyngeal space (Fig. 3). In addition, the patients age is consis-tent with this diagnosis, because the median age at onset is 19 years.6 Approximately 6% of patients have intracranial complications, which would also meet the definition of distant (metastatic) infection.

The administration of antibiotic agents may have decreased the likelihood of establishing a microbiologic diagnosis; however, negative cul-tures increase the likelihood of the presence of an organism such as fusobacterium, a fastidious anaerobe that may require an incubation period of 5 to 8 days before detection. Clindamycin and meropenem would both be expected to provide adequate antibacterial coverage, but it is impor-tant to recognize that the symptoms of Lemierres syndrome may progress despite adequate antibi-otic therapy.

Deficit on Abduction of the Right Eye

How does a deficit on ocular abduction help to explain the pathophysiology of the syndrome seen in this patient? To further define this pro-cess, it is important to understand ocular anat-omy, especially the structures along the pathway of the abducens nerve, which controls ocular abduction. The abducens nerve runs just lateral to the sphenoid, pierces the dura, and continues forward between the dura and the apex of the petrous bone.7 The nerve makes a sharp angle and enters the cavernous sinus before piercing the orbit and the deep surface of the lateral rectus muscle. In this case, there were no intraparen-chymal deficits involving the pons or abducens nucleus on imaging. However, there was dural enhancement, inflammation of the lateral rectus





Figure 3. Anatomical Features of Laterally Invasive Pharyngeal Infection.

The parapharyngeal space has an inverted triangular shape and is bound medially by the pharyngeal wall, superiorly by the base of the skull, laterally by the deep lobe of the parotid gland and mandibular ramus, and inferiorly by the hyoid bone. The thick arrow shows the likely route of infection from the site of initial invasion to the carotid sheath. The thin arrows show the interaction between lymphatic and vascular contents of the carotid sheath and those of the orbital and facial structures. Either hematogenous or lymphatic spread of fusobacterium is thought to result in metastatic infection. Septic lymph may cause perivascular inflammation and luminal thrombosis.

Parotid gland

Hyoid bone

Lymph node

Lateral rectus muscle

Abducens nerve

Base of skull (sphenoid bone)

Pharyngeal wall (route of initial invasion)

Mandibular ramus

Facial artery

Facial vein

Externaljugular vein

Posterior facial vein

Reflected sternocleidomastoid

muscle

Parapharyngeal space

Base of skull

Front view

Parotid gland

Mandible

Hyoid bone

Pharyngeal wall

Internaljugular vein

Vagus nerve

Internalcarotid artery

Deepcervical nodes

Commoncarotid artery

Carotid sheath





muscle, and possible cavernous-sinus involvement. Paralysis of the lateral rectal muscle due to or-bital impingement, inflammation of the muscle itself, or involvement of the peripheral abducens nerve may have resulted in the deficit.

Sarcoidosis, myasthenia gravis, or the Miller Fischer syndrome (a variant of the GuillainBarr syndrome) may cause a unilateral deficit on ocu-lar abduction. However, in this patient, the rap-idly progressive symptoms and associated fevers point toward infectious causes. Mycobacterium tu-berculosis may cause inflammation of the parotid gland, involvement of the basilar meninges, and isolated abducens-nerve palsies. However, it is highly unusual for M. tuberculosis infection to have such a fulminant course, and this patient had no known exposure history. Gradenigos syndrome, characterized by the triad of otorrhea, retro-or-bital pain, and palsy of the lateral rectus muscle, is caused by petrosal osteomyelitis associated with suppurative otitis media and mastoiditis. In this case, however, Gradenigos syndrome is an unlikely diagnosis, since the patient did not have a history of auricular pain consistent with chron-ic otitis media, and the imaging studies did not indicate mastoiditis or petrous osteomyelitis.

A diagnosis of EBV mononucleosis alone is not consistent with the fulminant and progres-sive disease course in this case; however, it is important to note that serologic testing did pro-vide evidence of recent primary EBV infection. The detection of IgM antibodies to EBV-specific viral capsid antigen is virtually diagnostic of primary infection,8 and the presence of IgG an-tibodies to EBV-specific viral capsid antigen and to EBV nuclear antigen indicates that the onset of infection occurred at least 3 weeks earlier. Although it is normal to find fusobacterium in the oral cavity, the bacteria may become patho-genic after an oropharyngeal infection.9 Approxi-mately 10% of cases of invasive fusobacterium infection are preceded by EBV infection.10

Finally, it is necessary to rule out the diagno-sis of bulimia nervosa in an 18-year-old woman with marked hypoalbuminemia, radiographic findings suggestive of poor dentition, and inflam-mation of the parotid gland. However, in patients with bulimia nervosa, swelling of the parotid gland is normally painless and bilateral, and den-tal findings usually include diffuse enamel loss and caries. Furthermore, the serum albumin level is usually normal in patients with eating disorders, even in those who are severely mal-

nourished.11 Hypoalbuminemia is frequently a marker of critical illness and has been described in patients with Lemierres syndrome.

My leading diagnosis in this case is Lemierres syndrome due to an invasive fusobacterium in-fection that developed shortly after primary EBV mononucleosis. The diagnosis of Lemierres syn-drome can be confirmed on the basis of either definitive evidence of thrombophlebitis or a cul-ture growing fusobacterium.

Dr. Eric S. Rosenberg (Pathology): Dr. Sen and Dr. Freitag, would you tell us your clinical impres-sions when you initially evaluated this patient?

Dr. Pritha Sen (Infectious Diseases): On the basis of the clinical history, physical examina-tion, and radiographic findings, our impression was that this patient had an acute pharyngitis that led to a suppurative infection of the parotid gland. Furthermore, we thought that this infec-tion extended along the vasculature originating in the parotid gland to the right inferotemporal dural space and to the subperiosteal space of the superior lateral orbit, causing abscess formation, and that an abscess in the subperiosteal space of the right lateral orbit caused the cranial-nerve deficit. Given the pharyngitis and evidence of infection involving the parotid gland, lateral or-bit, and dura, we were concerned about oral and odontogenic sources of infection of the head and deep neck. Consequently, we chose to administer vancomycin, meropenem, and clindamycin, anti-microbial agents directed against gram-positive, oral gram-negative, and anaerobic organisms that can penetrate the central nervous system. All cultures were sterile at the time of our initial evaluation and there was no clear evidence of thrombosis of the vasculature of the head and neck, but on the basis of the patients presenta-tion, we suspected Lemierres syndrome due to F. necrophorum. Our recommendations included expedited ophthalmologic evaluation for surgi-cal drainage of the right subperiosteal lateral orbital abscess and otolaryngologic evaluation of the abscesses in the parotid gland. Given our concern about Lemierres syndrome or a similar disorder, we also recommended additional im-aging studies of the head and neck to evaluate the patient for jugular-vein thrombosis and cav-ernous-sinus thrombosis.

Dr. Suzanne K. Freitag: On initial consultation with the ophthalmic plastic surgery service, we noted that the patients right eye had decreased visual acuity, a deficit on abduction, and perior-





bital edema, erythema, and tenderness. Given these findings, in conjunction with the findings on imaging studies and her worsening clinical course, we made the decision to proceed with urgent drainage of the orbital abscess. A supero-lateral orbitotomy was performed through a crease of the right upper eyelid. The subperios-teal dissection yielded a small amount of green purulent material, which was cultured.

Clinic a l Di agnosis

Lemierres syndrome, complicated by an orbital abscess.

Dr . K r is ti a n R . Ol sons Di agnosis

Lemierres syndrome due to Fusobacterium nec-rophorum.

Pathol o gic a l Discussion

Dr. John A. Branda: The diagnostic procedures in-cluded collection of specimens from several sites for routine aerobic and anaerobic bacterial culture. F. necrophorum, a highly pleomorphic gram-nega-tive rod, was isolated from the anaerobic compo-nent of two blood cultures (two of four bottles), an aspirate of the parotid-gland abscess, and a sample of the orbital fluid. Monomicrobial in-fection with F. necrophorum is frequently seen in patients with Lemierres syndrome.6

On the basis of the patients clinical presenta-tion and the usual pathogenesis of Lemierres syndrome,12 it is likely that the initial site of in-fection in this case was the pharynx. There is evi-dence that EBV mononucleosis and group C strep-tococcal pharyngitis are independent risk factors for the development of pharyngeal F. necrophorum infection.6,12,13 Both a recent EBV infection and a group C streptococcal infection were reported in this patient, and it is possible that these infec-tions predisposed her to the invasive F. necropho-rum infection that ultimately developed.

Hospi ta l Cour se

Dr. Emily B. Rubin (Pediatrics): After the patient un-derwent drainage of the subperiosteal abscess, she was admitted to the pediatrics department of this hospital. On the night of admission, she

had periorbital swelling of the left eye, increas-ing facial pain, and worsening right lateral gaze palsy. Because of the rapid development of these symptoms, we performed additional imaging studies.

Dr. Johnson: CT angiography and venography were performed, followed by MRI of the head, neck, and orbits, with and without the adminis-tration of contrast material (Fig. 4). These stud-ies revealed extensive thrombophlebitis of the right facial vein. There was also extensive bilat-eral arteritis of the intracranial internal carotid arteries, including a small mural thrombus in the right cavernous carotid artery. Postoperative changes in the right orbit and cavernous-sinus thrombophlebitis were also present. There was persistent basilar and temporal meningitis on the right side.

Dr. Rubin: Because of the severe narrowing of the carotid arteries that was seen on these imag-ing studies, the patient was transferred to the pediatric intensive care unit, where she received anticoagulant and antiplatelet therapy. She had a good response to the treatment. Repeat imaging of the head showed several small infarcts dis-tributed in the right middle cerebral artery, and it was unclear whether the cause of the infarcts was embolic or ischemic. Despite these findings, the patient had no neurologic deficits other than an inability to abduct her right eye. She was transferred back to the pediatrics inpatient ser-vice on day 9 and was discharged on day 15; medications at discharge included vancomycin (intravenous), meropenem, low-molecular-weight heparin (dalteparin sodium), and aspirin. Five days later, she was readmitted with fever and a rash, which were thought to be caused by the antibiotics, and she was transitioned to clindamy-cin. On discharge from the hospital, she was taking warfarin. Imaging of the head that was performed 3 months after her initial admission showed an expected evolution of the infarcts of the right middle cerebral artery and no sequelae of the carotid arteritis. The warfarin was discon-tinued after 4 months.

Dr. John B. Miller (Ophthalmology): After the patient was discharged, she was referred to the pediatric ophthalmology department for man-agement of her diplopia associated with persis-tent palsy of the right sixth cranial nerve. After 7 weeks and with minimal improvement, the decision was made to inject 5 units of botulinum





toxin in order to weaken the right medial rectus muscle.14 This immediately improved her ocular alignment in primary gaze. Four weeks later, she had full extraocular motility, and the diplopia had resolved.

Fina l Di agnosis

Lemierres syndrome caused by Fusobacterium necrophorum, with cavernous-sinus thrombophle-

bitis, carotid-artery thromboarteritis, and abscess-es of the parotid gland and subperiosteal orbit.

Presented at the Medical Case Conference.Dr. Olson reports receiving grant support through his institution

from Vodafone Foundation and the Omidyar Network. No other potential conflict of interest relevant to this article was reported.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank Dr. Michael H. Lev (Radiology, Massachusetts Gen-eral Hospital) and Dr. John B. Miller (Ophthalmology, Massa-chusetts Eye and Ear Infirmary) for their contributions to this article.

Figure 4. Additional Imaging Studies of the Head and Neck.

CT angiography and venography of the head and neck, as well as MRI of the head and neck (with and without the administration of contrast material), performed on the current admission, revealed findings suggestive of extensive thrombophlebitis of the right facial vein, cavernoussinus thrombophlebitis, and bilateral arteritis. A curved, multiplanar, reformatted image of the neck shows extensive thrombophlebitis of the right facial vein (Panel A, arrows). An axial T2weighted image shows hyperintense material in the orifices of the facial vein (Panel B, arrow), a finding consistent with thrombus. A coronal T1weighted, fatsaturated image (obtained after the administration of contrast material) shows bilateral cavernoussinus thrombophlebitis (Panel C, arrows) and findings suggestive of basilar and temporal meningitis. An axial T1weighted, fatsaturated image (obtained after the administration of contrast material) shows evidence of bilateral arteritis, including abnormal enhancement of the petrous internal carotid arteries (Panel D, arrow). An axial image obtained at the level of the right cavernous internal carotid artery shows evidence of arteritis, as well as a focus of thrombus along the vessel wall (Panel E, arrow). An axial image shows cavernoussinus thrombophlebitis, which is greater on the right side than on the left (Panel F, arrows).

A B C

E FD





References1. Alcaide ML, Bisno AL. Pharyngitis and epiglottitis. Infect Dis Clin North Am 2007; 21: 449-69.2. Hurt C, Tammaro D. Diagnostic eval-uation of mononucleosis-like illnesses. Am J Med 2007; 120(10): 911.e1-8.3. Hunt DP, Thabet A, Rosenberg ES. Case Records of the Massachusetts Gen-eral Hospital (Case 29-2010). N Engl J Med 2010; 363: 1266-74.4. Shah M, Centor RM, Jennings M. Se-vere acute pharyngitis caused by group C streptococcus. J Gen Intern Med 2007; 22: 272-4.5. Update: mumps outbreak New York and New Jersey, June 2009January 2010. MMWR Morb Mortal Wkly Rep 2010; 59: 125-9.6. Riordan T. Human infection with Fu-

sobacterium necrophorum (Necrobacillo-sis), with a focus on Lemierres syndrome. Clin Microbiol Rev 2007; 20: 622-59.7. Wilson-Pauwels L, Akesson EJ, Stew-ard PA. Cranial nerves: anatomy and clin-ical comments. Philadelphia: B.C. Decker, 1988.8. Luzuriaga K, Sullivan JL. Infectious mononucleosis. N Engl J Med 2010; 362: 1993-2000.9. Smith GR, Wallace LM, Noakes DE. Experimental observations on the patho-genesis of necrobacillosis. Epidemiol In-fect 1990; 104: 73-8.10. Ramirez S, Hild TG, Rudolph CN, et al. Increased diagnosis of Lemierre syn-drome and other Fusobacterium necroph-orum infections at a Childrens Hospital. Pediatrics 2003; 112(5): e380.

11. Winston AP. The clinical biochemis-try of anorexia nervosa. Ann Clin Bio-chem 2012; 49: 132-43.12. Kuppalli K, Livorsi D, Talati NJ, Os-born M. Lemierres syndrome due to Fu-sobacterium necrophorum. Lancet Infect Dis 2012; 12: 808-15.13. Jensen A, Hagelskjaer Kristensen L, Prag J. Detection of Fusobacterium nec-rophorum subsp. funduliforme in tonsil-litis in young adults by real-time PCR. Clin Microbiol Infect 2007; 13: 695-701.14. Scott AB. Botulinum toxin injection of eye muscles to correct strabismus. Trans Am Ophthalmol Soc 1981; 79: 734-70.Copyright 2014 Massachusetts Medical Society.

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