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Letters to the Editor

References 1 Restellim S, Kherad O, Jairath V, Martel M, Barkun AN. Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding. Aliment Pharmacol Ther 2013; 37: 316–22. 2 Taha AS, McCloskey C, Craigen T, Angerson W, Shah AA, Morran CG. Mortality following blood transfusion for non-variceal upper gastrointestinal

bleeding. Frontline Gastroenterol 2011; 2: 218–25. 3 Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368: 11–21. 4 Hearnshaw SA, Logan RFA, Palmer KA, Card TA, Travers SPL, Murphy MF. Outcomes following early red blood cell transfusion in acute upper gastrointestinal bleeding. Aliment Pharmacol Ther 2012; 32: 215–24.

5 Anonymous. Patient Blood Management Guidelines: Module 3. Medical. Canberra: National Blood Authority; 2012. 6 Isbister JP, Shander A, Spahn DR, Erhard J, Farmer SL, Hofmann A. Adverse blood transfusion outcomes: establishing causation. Transfus Med 2011; 25: 89–101. 7 Bradford Hill A. The environment and disease: association or causation. Proc R Soc Med 1965; 58: 295–300.

General correspondence Cavernous sinus syndrome: a rare complication of neurosyphilis Saunderson and Chan have provided interesting data in their recent article.1 Another rare and severe complication of neurosyphilis is cavernous sinus syndrome. Syphilitic cavernous sinus syndrome may occur at any age. For instance, Noel et al. have reported it in individuals as old as 62 years of age.2 The right and left cavernous sinuses are equally affected. Interestingly, males are almost twice as likely to develop neurosyphilis when compared with females. For instance, Clark and Danbolt in the recent ‘Oslo study’ reported that the incidence rate in males was 9.4% compared with 5% in females.3 The past few years have seen the appearance of neurosyphilis in several atypical forms. For instance, Mitsonis et al. in a recent retrospective review reported that 68.6% of cases of neurosyphilis presented in typical forms from 1965 to 1984, while 85.7% of cases presented in atypical forms during the 10-year duration preceding 2005.4 Multiple cranial nerve palsies may be seen as a result of syphilitic cavernous sinus syndrome. In particular, the most susceptible nerves are the III, IV, V and VI cranial nerves.5 At least two or more nerves should be involved, or only one nerve may be involved (with computed tomography- or magnetic resonance imaging (MRI)-confirmed lesion of the cavernous sinus), for making a formal diagnosis of cavernous sinus syndrome.6 Patients may complain of diplopia as well as ptosis. Nadgir et al. have reported complete ophthalmoplegia in a 50-year-old patient secondary to syphilitic cavernous sinus syndrome.7 In addition, most patients report a headache localised to the frontal area. V cranial nerve involvement may result in facial numbness.8 Simultaneous cardiovascular involvement in the form of aortitis may be 428

seen in some cases of syphilitic cavernous sinus syndrome. It should be noted that in general most cases of cavernous sinus syndrome are non-infectious. For instance, Keane in a recent study reported that nearly 30% of cases were secondary to intracranial tumours, while only 23% were secondary to intracranial infection.9 Fernández et al. in another recent study have reported that involvement of the V2 branch, as well as male sex, is more suggestive of underlying tumour aetiology.10 MRI of the brain usually reveals a mass or gumma (hyperintensity lesion on T-2 imaging) within the cavernous sinus.6 Syphilitic gumma may easily be mistaken for intracranial tumours. Serum as well as CSF VDRL may be positive. Interestingly, Fargen et al. have recently reported that only 64% of patients with neurosyphilis have a positive CSF syphilis test.11 Confirmatory ‘fluorescent treponemal antibody’ tests should be done. In addition, CSF evaluation usually reveals normal glucose as well as protein levels. Accompanying CSF neutrophil pleocytosis may be seen. HIV testing should be done in all patients with syphilitic cavernous sinus syndrome. In fact, Schofer et al. in a recent study reported neurosyphilis in 16% of patients with HIV and concurrent active syphilis.12 Administration of aqueous crystalline penicillin G may result in complete resolution of the symptoms. The recommended dose is 4 × 106 units every 4 h. Standard duration of treatment is 14 days.4 This may be followed by 2.4 million units of penicillin administered weekly for the next 3 weeks. Post-treatment MRI usually shows complete resolution of the thrombus. Symptomatic relief may be seen as soon as within 4 days of initiating antibiotic therapy. Fleet et al. have also reported success with steroid therapy in resolving syphilitic intracranial mass-like lesions.3,13 © 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians

Letters to the Editor

As is obvious from the above discussion, cavernous sinus syndrome is a rare presentation of tertiary syphilis. It should be considered in the differential in patients with neurosyphilis presenting with cranial nerve palsies.

References 1 Saunderson R, Chan R. Mesiotemporal changes on magnetic resonance imaging in neurosyphilis. Intern Med J 2012; 42: 1057–63. 2 Noel CB, Moeketsi K, Kies B. Cavernous sinus syndrome, an atypical presentation of tertiary syphilis: case report and review of the literature. Clin Neurol Neurosurg 2011; 113: 65–7. 3 Clark EG, Danbolt N. The Oslo study of the natural history of untreated syphilis; an epidemiologic investigation based on a restudy of the BoeckBruusgaard material; a review and appraisal. J Chronic Dis 1955; 2: 311–44. 4 Mitsonis CH, Kararizou E, Dimopoulos N, Triantafyllou N, Kapaki E, Mitropoulos P et al. Incidence and clinical presentation of neurosyphilis: a retrospective study of 81 cases. Int J

Received 2 December 2013; accepted 12 December 2013. doi:10.1111/imj.12356

S. Kapoor Private Practice, Mechanicsville, Virginia, USA

Neurosci 2008; 118: 1251–7. 5 Boonyawiroj S, Phanthumchinda K. Extensive anterior cranial fossa idiopathic hypertrophic pachymeningitis: a case report and review of the literature. J Med Assoc Thai 2005; 88: 1934–40. 6 Shigemi J, Sato S, Hasegawa S, Shibayama H, Maki H, Ouchi T. A case of meningo-vascular type neurosyphilis presenting oculomotor nerve paralysis with interesting MRI findings. Nihon Naika Gakkai Zasshi 1995; 84: 1163–5. 7 Nadgir D, Ramdas R, Kulkarni R, Oak P, Shah A. Cavernous sinus syndrome due to syphilitic pachymeningitis. Neurol India 2003; 51: 289–90. 8 Lapresle J, Desi M. Painful ophthalmoplegia (author’s translation). Acta Neurol Belg 1977; 77: 331–50. 9 Keane JR. Cavernous sinus syndrome:

Author reply At the turn of the 20th century, Sir William Osler said, ‘He who knows syphilis, knows medicine’. Whilst generations of medical students have been taught the protean manifestations of syphilis, until recently, the modern physician was less well acquainted with the myriad of ways it can present. However, the past decade has seen an increase in the rates of syphilis, renewing interest and consideration of syphilis as a differential diagnosis in varied presentations. Recently, Kapoor1 reported a case of neurosyphilis complicated by cavernous sinus syndrome and highlighted the need to consider this as a differential in patients with neurosyphilis presenting with cranial nerve palsies. However, patients with the cranial nerve palsies typically seen in the cavernous sinus syndrome are likely to

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analysis of 151 cases. Arch Neurol 1996; 53: 967. Fernández S, Godino O, MartínezYélamos S, Mesa E, Arruga J, Ramón JM et al. Cavernous sinus syndrome: a series of 126 patients. Medicine 2007; 86: 278–81. Fargen KM, Alvernia JE, Lin CS, Melgar M. Cerebral syphilitic gummata: a case presentation and analysis of 156 reported cases. Neurosurgery 2009; 64: 568–76. Schöfer H, Imhof M, Thoma-Greber E, Brockmeyer NH, Hartmann M, Gerken G et al. Active syphilis in HIV infection: a multicentre retrospective survey. The German AIDS Study Group (GASG). Genitourin Med 1996; 72: 176–81. Fleet WS, Watson RT, Ballinger WE. Resolution of a gumma with steroid therapy. Neurology 1986; 36: 1104–7.

have undergone brain imaging during their diagnostic work-up; is it not more likely that patients are diagnosed with cavernous sinus syndrome before the diagnosis of neurosyphilis, and therefore, syphilis needs to be considered as a differential in patients with cavernous sinus syndrome? Importantly, the diagnosis of syphilitic cavernous sinus syndrome will be difficult from syphilis serology testing alone, given that syphilitic seropositivity is more common than cavernous sinus syndrome. Received 31 January 2014; accepted 11 February 2014. doi:10.1111/imj.12388

R. B. Saunderson and R. C. Chan Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, NSW, Australia

Reference 1 Kapoor S. Cavernous sinus syndrome: a rare complication of neurosyphilis. Intern Med J 2014; 44: 428–9.

© 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians

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Cavernous sinus syndrome: a rare complication of neurosyphilis.

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