Journal of the Neurological Sciences 344 (2014) 219–220
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Unilateral mydriatic tonic pupil as an early isolated symptom of neurosyphilis Keywords: Neurosyphilis Unilateral tonic pupil Adie tonic pupil Oculomotor nerve Denervation supersensitivity
Dear Editors Pupillary abnormalities are observed in nearly half of patients with syphilis and are the most important early ocular sign [1]. The most common pupillary abnormality associated with neurosyphilis is Argyll Robertson pupils, which are small pupils, almost always bilateral, that constrict properly and apparently normally when focusing on a near object but that constrict poorly or not at all to direct light [2]. Meanwhile, it is estimated that 8–17% of tonic pupils showing dilation and diminished accommodative power are caused by infection with Treponema pallidum, such as tabes dorsalis, general paresis, syphilitic optic neuropathy, and latent syphilis [3]. It has also been reported that the isolated unilateral tonic pupil is rarely found at an earlier stage of neurosyphilis [1,4–6]. Therefore, efforts focused on the unilateral tonic pupil rather than bilateral tonic pupils may enable the early diagnosis of neurosyphilis and may improve the effects of therapy. We describe a young male patient with neurosyphilis presenting with isolated unilateral tonic pupil. Early penicillin therapy substantially improved both the pupillary abnormality and ocular symptoms caused by the tonic pupil. A 30-year-old man was admitted to our hospital in February 2013 for a left mydriasis of unknown etiology. One month earlier, he had experienced blurred vision and noticed the left mydriasis in the mirror. During a subsequent visit to a neurosurgical clinic, a neurosurgical examination ruled out a cerebral aneurysm. In a general physical examination during his initial visit with us, he showed no abnormal findings. He was alert and had a Mini-Mental State Examination (MMSE) score of 30/30. He revealed no abnormality except for the ophthalmic findings described below. His best-corrected decimal visual acuity tested by the Landolt ring chart was 1.5 bilaterally (approximately corresponding to 20/12.5 of fractional visual acuity). Under illumination, his right and left pupils were 3 and 7 mm in diameter, respectively (Fig. 1). Light reflex was observed in the right pupil but not in the left. The left pupil constricted tonically on near response. With the ophthalmic instillation of dilute pilocarpine (0.125%), the left pupil constricted to 4 mm but the right pupil remained unchanged (Fig. 1). Neither ptosis nor impaired ocular movement was observed. Laboratory test results were normal except for some abnormalities in the results of his serological tests for syphilis, as follows: there was an elevation of serum rapid plasma reaction (RPR) to 124 RU (normal range b 1 RU) and T. pallidum hemagglutination assay (TPHA) to 20,480 TU (normal range b 10 TU). A serum
http://dx.doi.org/10.1016/j.jns.2014.06.007 0022-510X/© 2014 Elsevier B.V. All rights reserved.
test for antibodies against human immunodeficiency virus type 1 (HIV1) was negative. Cerebrospinal fluid (CSF) examination showed elevated cell count (mononuclear cells 45/μl and polynuclear cells 1/μl) and protein (57 mg/dl) with positive findings of RPR (3.3RU) and TPHA (1:640 titer). He had visited commercial sex workers every few months 10 years earlier. His medical history was normal. Gadolinium-enhanced MRI of the brain showed no abnormalities. The patient was diagnosed as having neurosyphilis on the basis of positive RPR and TPHA as well as the elevated cell count and protein in the CSF. He received two courses of penicillin G (24 million units/day, 14 days) for 5 weeks. Six months later, his blurred vision disappeared. Under illumination, his right and left pupils were 4 and 5 mm in diameter, respectively. The bilateral pupils reacted promptly to light. The blunt response of the left pupil on near response showed a slight improvement. CSF examination showed improvements in cell count (3/μl) and RPR (0.5 U) but not in protein level (60 mg/dl). The left pupil in this patient showed mydriasis, no pupillary response to light, and slow pupillary constriction on near response. In addition, the left pupil following dilute pilocarpine instillation showed a marked constriction, suggesting cholinergic denervation supersensitivity of the iris sphincter due to damage to the ciliary ganglion or postganglionic short ciliary nerves. In conjunction with the CSF findings suggesting neurosyphilis, a diagnosis of tonic pupil due to neurosyphilis was made. While the representative clinical condition of unilateral tonic pupil is Adie tonic pupil, 45% of cases of bilateral tonic pupils are caused by syphilis [3]. Adie tonic pupil, however, often extends to the second eye with time and then eventually becomes small [2]. Similarly, unilateral tonic pupil due to neurosyphilis could extend to the other side in only 2 months [6]. Although recently acquired tonic pupils are usually large, they tend to become miotic over the course of several years and to mimic Argyll Robertson pupils [2,3]. The tendency toward bilaterality and progressive miosis might be attributable to the progressive
A
B
R
L
R
L
Fig. 1. (A) Under illumination, the pupil was dilated on the left side (7 mm in diameter) but not on the right (3 mm in diameter). (B) After instillation of dilute pilocarpine (0.125%), the left pupil showed marked constriction, suggesting cholinergic denervation supersensitivity (4 mm in diameter). R: right; and L: left.
220
Letter to the Editor
degeneration of the ciliary ganglion over the years [7]. Thus, we need to note that pupil findings such as laterality and size depend on the duration of illness. Unilateral mydriatic tonic pupil would certainly be observed in the very early stage of neurosyphilis. Intravenous penicillin administration has been used for the treatment of isolated tonic pupil due to neurosyphilis [1,4–6,8]. After penicillin therapy in patients with bilateral tonic pupils, syphilis was cured but pupillary abnormalities remained unchanged [3,8]. On the other hand, in patients with unilateral tonic pupil, including our patient, subjective symptoms or pupillary signs completely or partially disappeared after therapy [1,6]. These findings suggest that unilateral pupillary abnormalities in the very early stage are reversible, probably due to the surviving ciliary ganglion neurons. These findings warrant aggressive examination for syphilis in all patients presenting with unilateral mydriatic tonic pupil. References [1] Gu X, Guan Z, Chai Z, Zhou P. Unilateral mydriasis as the primary sign of neurosyphilis. Infection 2014;42:215–7. [2] Thompson HS, Kardon RH. The Argyll Robertson pupil. J Neuroophthalmol 2006;26:134–8. [3] Fletcher WA, Sharpe JA. Tonic pupils in neurosyphilis. Neurology 1986;36:188–92. [4] Zeligs MA, Joseph GF. Unilateral internal ophthalmoplegia; sole clinical sign in patient with syphilitic meningitis. Arch Neurol Psychiatry 1945;54:389. [5] Camoriano GD, Kassab J, Suchak A, Gimbel HV. Neurosyphilis masquerading as an acute Adie's tonic pupil: report of a case. Case Rep Ophthalmol 2011;2:205–10. [6] Jivraj I, Johnson M. A rare presentation of neurosyphilis mimicking a unilateral Adie's tonic pupil. Semin Ophthalmol 2014;29:189–91. [7] Thompson HS. Adie syndrome: some new observations. Trans Am Ophthalmol Soc 1977;75:587–626. [8] Sakai T, Shikishima K, Mizobuchi T, Yoshida M, Kitahara K. Bilateral tonic pupils associated with neurosyphilis. Jpn J Ophthalmol 2003;47:368–71.
Tadayuki Takata Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Kagawa, Japan Masaki Kamada Kazuyo Ikeda Department of Neurological Intractable Disease Research, Kagawa University Faculty of Medicine, Kagawa, Japan Kodai Kume Yohei Kokudo Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Kagawa, Japan Tetsuo Touge Department of Health Sciences, Kagawa University Faculty of Medicine, Kagawa, Japan Kazushi Deguchi⁎ Tsutomu Masaki Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Kagawa, Japan ⁎Corresponding author at: Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Tel.: +81 87 891 2156; fax: +81 87 891 2158. E-mail address: [email protected]. 17 March 2014
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Unilateral mydriatic tonic pupil as an early isolated symptom of neurosyphilis Keywords: Neurosyphilis Unilateral tonic pupil Adie tonic pupil Oculomotor nerve Denervation supersensitivity
Dear Editors Pupillary abnormalities are observed in nearly half of patients with syphilis and are the most important early ocular sign [1]. The most common pupillary abnormality associated with neurosyphilis is Argyll Robertson pupils, which are small pupils, almost always bilateral, that constrict properly and apparently normally when focusing on a near object but that constrict poorly or not at all to direct light [2]. Meanwhile, it is estimated that 8–17% of tonic pupils showing dilation and diminished accommodative power are caused by infection with Treponema pallidum, such as tabes dorsalis, general paresis, syphilitic optic neuropathy, and latent syphilis [3]. It has also been reported that the isolated unilateral tonic pupil is rarely found at an earlier stage of neurosyphilis [1,4–6]. Therefore, efforts focused on the unilateral tonic pupil rather than bilateral tonic pupils may enable the early diagnosis of neurosyphilis and may improve the effects of therapy. We describe a young male patient with neurosyphilis presenting with isolated unilateral tonic pupil. Early penicillin therapy substantially improved both the pupillary abnormality and ocular symptoms caused by the tonic pupil. A 30-year-old man was admitted to our hospital in February 2013 for a left mydriasis of unknown etiology. One month earlier, he had experienced blurred vision and noticed the left mydriasis in the mirror. During a subsequent visit to a neurosurgical clinic, a neurosurgical examination ruled out a cerebral aneurysm. In a general physical examination during his initial visit with us, he showed no abnormal findings. He was alert and had a Mini-Mental State Examination (MMSE) score of 30/30. He revealed no abnormality except for the ophthalmic findings described below. His best-corrected decimal visual acuity tested by the Landolt ring chart was 1.5 bilaterally (approximately corresponding to 20/12.5 of fractional visual acuity). Under illumination, his right and left pupils were 3 and 7 mm in diameter, respectively (Fig. 1). Light reflex was observed in the right pupil but not in the left. The left pupil constricted tonically on near response. With the ophthalmic instillation of dilute pilocarpine (0.125%), the left pupil constricted to 4 mm but the right pupil remained unchanged (Fig. 1). Neither ptosis nor impaired ocular movement was observed. Laboratory test results were normal except for some abnormalities in the results of his serological tests for syphilis, as follows: there was an elevation of serum rapid plasma reaction (RPR) to 124 RU (normal range b 1 RU) and T. pallidum hemagglutination assay (TPHA) to 20,480 TU (normal range b 10 TU). A serum
http://dx.doi.org/10.1016/j.jns.2014.06.007 0022-510X/© 2014 Elsevier B.V. All rights reserved.
test for antibodies against human immunodeficiency virus type 1 (HIV1) was negative. Cerebrospinal fluid (CSF) examination showed elevated cell count (mononuclear cells 45/μl and polynuclear cells 1/μl) and protein (57 mg/dl) with positive findings of RPR (3.3RU) and TPHA (1:640 titer). He had visited commercial sex workers every few months 10 years earlier. His medical history was normal. Gadolinium-enhanced MRI of the brain showed no abnormalities. The patient was diagnosed as having neurosyphilis on the basis of positive RPR and TPHA as well as the elevated cell count and protein in the CSF. He received two courses of penicillin G (24 million units/day, 14 days) for 5 weeks. Six months later, his blurred vision disappeared. Under illumination, his right and left pupils were 4 and 5 mm in diameter, respectively. The bilateral pupils reacted promptly to light. The blunt response of the left pupil on near response showed a slight improvement. CSF examination showed improvements in cell count (3/μl) and RPR (0.5 U) but not in protein level (60 mg/dl). The left pupil in this patient showed mydriasis, no pupillary response to light, and slow pupillary constriction on near response. In addition, the left pupil following dilute pilocarpine instillation showed a marked constriction, suggesting cholinergic denervation supersensitivity of the iris sphincter due to damage to the ciliary ganglion or postganglionic short ciliary nerves. In conjunction with the CSF findings suggesting neurosyphilis, a diagnosis of tonic pupil due to neurosyphilis was made. While the representative clinical condition of unilateral tonic pupil is Adie tonic pupil, 45% of cases of bilateral tonic pupils are caused by syphilis [3]. Adie tonic pupil, however, often extends to the second eye with time and then eventually becomes small [2]. Similarly, unilateral tonic pupil due to neurosyphilis could extend to the other side in only 2 months [6]. Although recently acquired tonic pupils are usually large, they tend to become miotic over the course of several years and to mimic Argyll Robertson pupils [2,3]. The tendency toward bilaterality and progressive miosis might be attributable to the progressive
A
B
R
L
R
L
Fig. 1. (A) Under illumination, the pupil was dilated on the left side (7 mm in diameter) but not on the right (3 mm in diameter). (B) After instillation of dilute pilocarpine (0.125%), the left pupil showed marked constriction, suggesting cholinergic denervation supersensitivity (4 mm in diameter). R: right; and L: left.
220
Letter to the Editor
degeneration of the ciliary ganglion over the years [7]. Thus, we need to note that pupil findings such as laterality and size depend on the duration of illness. Unilateral mydriatic tonic pupil would certainly be observed in the very early stage of neurosyphilis. Intravenous penicillin administration has been used for the treatment of isolated tonic pupil due to neurosyphilis [1,4–6,8]. After penicillin therapy in patients with bilateral tonic pupils, syphilis was cured but pupillary abnormalities remained unchanged [3,8]. On the other hand, in patients with unilateral tonic pupil, including our patient, subjective symptoms or pupillary signs completely or partially disappeared after therapy [1,6]. These findings suggest that unilateral pupillary abnormalities in the very early stage are reversible, probably due to the surviving ciliary ganglion neurons. These findings warrant aggressive examination for syphilis in all patients presenting with unilateral mydriatic tonic pupil. References [1] Gu X, Guan Z, Chai Z, Zhou P. Unilateral mydriasis as the primary sign of neurosyphilis. Infection 2014;42:215–7. [2] Thompson HS, Kardon RH. The Argyll Robertson pupil. J Neuroophthalmol 2006;26:134–8. [3] Fletcher WA, Sharpe JA. Tonic pupils in neurosyphilis. Neurology 1986;36:188–92. [4] Zeligs MA, Joseph GF. Unilateral internal ophthalmoplegia; sole clinical sign in patient with syphilitic meningitis. Arch Neurol Psychiatry 1945;54:389. [5] Camoriano GD, Kassab J, Suchak A, Gimbel HV. Neurosyphilis masquerading as an acute Adie's tonic pupil: report of a case. Case Rep Ophthalmol 2011;2:205–10. [6] Jivraj I, Johnson M. A rare presentation of neurosyphilis mimicking a unilateral Adie's tonic pupil. Semin Ophthalmol 2014;29:189–91. [7] Thompson HS. Adie syndrome: some new observations. Trans Am Ophthalmol Soc 1977;75:587–626. [8] Sakai T, Shikishima K, Mizobuchi T, Yoshida M, Kitahara K. Bilateral tonic pupils associated with neurosyphilis. Jpn J Ophthalmol 2003;47:368–71.
Tadayuki Takata Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Kagawa, Japan Masaki Kamada Kazuyo Ikeda Department of Neurological Intractable Disease Research, Kagawa University Faculty of Medicine, Kagawa, Japan Kodai Kume Yohei Kokudo Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Kagawa, Japan Tetsuo Touge Department of Health Sciences, Kagawa University Faculty of Medicine, Kagawa, Japan Kazushi Deguchi⁎ Tsutomu Masaki Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Kagawa, Japan ⁎Corresponding author at: Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Tel.: +81 87 891 2156; fax: +81 87 891 2158. E-mail address: [email protected]. 17 March 2014
