Clinical Neurology and Neurosurgery 127 (2014) 42–43
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case Report
Vogt–Koyanagi–Harada disease with meningitis-retention syndrome and increased CSF adenosine deaminase levels Akiyuki Hiraga a,∗ , Yoko Takatsuna b , Ryuji Sakakibara c , Ikuo Kamitsukasa a , Masahiro Minamide d , Satoshi Kuwabara e a
Department of Neurology, Chiba Rosai Hospital, Chiba, Japan Department of Ophthalmology, Chiba Rosai Hospital, Chiba, Japan c Department of Neurology, Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan d Department of Urology, Chiba Rosai Hospital, Chiba, Japan e Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan b
a r t i c l e
i n f o
Article history: Received 15 December 2013 Received in revised form 19 August 2014 Accepted 24 September 2014 Available online 5 October 2014 Keywords: Vogt–Koyanagi–Harada disease Urinary retention Meningitis Adenosine deaminase
1. Introduction Vogt–Koyanagi–Harada (VKH) disease is a multisystem inflammatory disease affecting the eye, ear, skin and meninges [1,2]. The diagnosis of VKH disease could be confusing before the appearance of typical ophthalmological symptoms. Focal neurological signs are rare in VKH disease [1,2], and urological symptoms have not yet been described. We report a patient with VKH disease who presented a rare syndrome, such as meningitis-retention syndrome. Furthermore, we discuss the difficulty in diagnosing this disease due to increased adenosine deaminase (ADA) levels in the cerebrospinal fluid (CSF). 2. Case report In December 2012, a 67-year-old man developed severe headache 14 days before his admission, followed by appetite loss and fever. Four days before admission, he developed urinary voiding difficulty and urinary retention on the following
∗ Corresponding author at: Department of Neurology, Chiba Rosai Hospital, 2-16 Tatsumidai-Higashi, Ichihara-shi, Chiba 290-0003, Japan. Tel.: +81 436 74 1111; fax: +81 436 74 1151. E-mail address: [email protected] (A. Hiraga). http://dx.doi.org/10.1016/j.clineuro.2014.09.021 0303-8467/© 2014 Elsevier B.V. All rights reserved.
day and was therefore referred to the emergency room in our hospital. A Foley’s catheter was placed into his bladder. He was then admitted in the urology department. On admission, his body temperature was 37.6 ◦ C. Peripheral white blood cell count and haemoglobin 8200/L and 17.1 g/dL, respectively. Blood chemistry results revealed 25 IU/L of aspartate aminotransferase, 24 IU/L of alanine aminotransferase and 0.1 mg/dL of serum C-reactive protein. Although urinalysis showed no pathogen or white blood cells, urinary retention and fever seemed to be caused by urinary tract infection. An intravenous antibiotic therapy was initiated, but his symptoms did not ameliorate. Therefore, he was referred to the neurology department seven days after admission. During the initial neurological examination, he was alert and co-operative with no neck stiffness or Kernig’s sign. His pupils were equal with no limitation in the eye movements. Moreover, he had no facial-nerve palsy. His speech, muscle strength in the extremities, co-ordination, and sensory system were normal. CSF analysis revealed 75 white blood cells/mm3 (6% neutrophils and 94% lymphocytes), a glucose level of 77 mg/dL (simultaneous blood sugar 178 mg/dL) and a protein level of 81 mg/dL. Polymerase chain reaction analysis of CSF was negative for tuberculosis. CSF cultures and cytological CSF examination showed no pathogens and negativity for the CSF cryptococcal antigen. We subsequently found that the CSF ADA levels increased to 12.9 U/L, and CSF viral titres were negative. Cranial computed tomography showed no intracranial abnormality.
A. Hiraga et al. / Clinical Neurology and Neurosurgery 127 (2014) 42–43
Fig. 1. Fluorescein angiography of the right eye analysed 36 days after the onset of neurological symptoms. It reveals disclosed and multiple choroidal leakage and mild disc hyperfluorescence.
His clinical history, physical examination and elevated CSF lymphocytes were consistent with the diagnosis of aseptic meningitis (meningitis-retention syndrome). However, conservative therapy did not improve his symptoms. On the 16th day after admission, the pleocytosis was practically unchanged (85/mm3 ) in the second CSF samples, and the glucose levels decreased to 58 mg/dL (blood sugar 159 mg/dL), which was incompatible with the aseptic meningitis. We suspected tuberculous meningitis, and oral isoniazid, rifampicin and pyrazinamide were initially administered 16 days after admission. However, his symptoms did not ameliorate, and the patient noticed a perception of floaters in the left eye 20 days after admission. Ophthalmological examination on 23 days after admission showed that the visual acuity was 1.0 in the right eye and 0.7 in the left eye. Fundus examination revealed optic disc hyperaemia in both eyes. In a slit-lamp examination, no anterior chamber cells were observed, but keratic precipitates were found. Fluorescein angiography revealed optic nerve staining and multiple choroidal leakages in both eyes (Fig. 1). VKH disease was diagnosed, and methylprednisolone (1 g per day for 3 days) was intravenously administered from the 23rd day after admission. Marked clinical improvements were observed within a day after the initiation of corticosteroid therapy, which dramatically resolved headache, appetite loss and visual symptoms. CSF pleocytosis and ADA levels recovered in parallel with his clinical symptoms. The patient was discharged 2 months after admission.
43
phase, the acute ocular or uveitic phase begins [1,2]. However, the patient showed uveitic phase 34 days after the onset of headache, making the early diagnosis of VKH disease difficult. Elderly patients (65 years and over) with VKH disease have become more frequent in recent years [3]. Therefore, neurologists should include VKH disease in the differential diagnosis for etiologically undiagnosed meningitis in elderly patients. No case of VKH disease with meningitis-retention syndrome has been previously reported. However, combination of acute urinary retention and aseptic meningitis was reported as a case of meningitis-retention syndrome [4]. Typical symptoms of meningitis-retention syndrome are fever, headache and stiff neck with/without minor pyramidal signs together with acute urinary retention. Because meningitis-retention syndrome has a benign and self-remitting course [4], we preliminarily selected conservative therapies during the initial neurological examination. Meningitis-retention syndrome seemed to be an extremely mild form of acute disseminated encephalomyelopathy, and the lesion site of meningitis-retention syndrome has been suggested to be at the spinal cord. Because the patient had no other neurological symptoms suggesting spinal cord involvement and urodynamic studies were not performed, the underlying mechanism of meningitis-retention syndrome in VKH disease was unclear. However, our case suggests that VKH disease can present urinary retention presumably due to the spinal cord involvement. Another major concern was the increased CSF ADA levels. The CSF ADA estimation seemed to be useful in the diagnosis of tuberculous meningitis. Although non-tuberculous infectious meningitis, such as pyogenic meningitis, could elevate the CSF ADA levels, noninfectious neurologic diseases commonly could not elevate it [5]. However, clinical features of CSF in our patient did not show any evidence which indicates infectious meningitis. In conclusion, VKH disease should be listed in the differential diagnosis of meningitis-retention syndrome, which may precede uveitis in this inflammatory disorder. Moreover, it may present as an acute or subacute lymphocytic meningitis with increased CSF ADA and glucose consumption in CSF. Although these results indicate that the CSF ADA levels are not helpful to differentiate VKH disease from tuberculous meningitis, the differential diagnosis was extremely important because therapeutic strategies of VKH disease differ from aseptic or tuberculous meningitis. Conflict of interest We have no conflicts of interest. References
3. Discussion Our patient was diagnosed with VKH disease because of the combination of uveitis (appeared later) and meningitis. Furthermore, the patient was unique due to meningitis-retention syndrome and increased CSF ADA levels, both of which completely disappeared after corticosteroid therapy. Uveitis appeared 34 days after the onset of neurological symptoms. In general, VKH disease evolves in four phases: (1) prodromal, (2) uveitic, (3) convalescent and (4) chronic/recurrent. In the prodromal phase, patients develop headache and fever. From 3 days to 2 weeks after the prodromal
[1] Andreoli CM, Foster CS. Vogt–Koyanagi–Harada disease. Int Ophthalmol Clin 2006;46:111–22. [2] Pan D, Hirose T. Vogt–Koyanagi–Harada syndrome: review of clinical features. Semin Ophthalmol 2011;26:312–5. [3] Kiyomoto C, Imaizumi M, Kimoto K, Abe H, Nakano S, Nakatsuka K. Vogt–Koyanagi–Harada disease in elderly Japanese patients. Int Ophthalmol 2007;27:149–53. [4] Sakakibara R, Kishi M, Tsuyusaki Y, Tateno A, Tateno F, Uchiyama T, et al. “Meningitis-retention syndrome”: a review. Neurourol Urodyn 2013;32: 19–23. [5] Sun Q, Sha W, Xiao HP, Tian Q, Zhu H. Evaluation of cerebrospinal fluid adenosine deaminase activity for the differential diagnosis of tuberculous and nontuberculous meningitis. Am J Med Sci 2012;344:116–21.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case Report
Vogt–Koyanagi–Harada disease with meningitis-retention syndrome and increased CSF adenosine deaminase levels Akiyuki Hiraga a,∗ , Yoko Takatsuna b , Ryuji Sakakibara c , Ikuo Kamitsukasa a , Masahiro Minamide d , Satoshi Kuwabara e a
Department of Neurology, Chiba Rosai Hospital, Chiba, Japan Department of Ophthalmology, Chiba Rosai Hospital, Chiba, Japan c Department of Neurology, Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan d Department of Urology, Chiba Rosai Hospital, Chiba, Japan e Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan b
a r t i c l e
i n f o
Article history: Received 15 December 2013 Received in revised form 19 August 2014 Accepted 24 September 2014 Available online 5 October 2014 Keywords: Vogt–Koyanagi–Harada disease Urinary retention Meningitis Adenosine deaminase
1. Introduction Vogt–Koyanagi–Harada (VKH) disease is a multisystem inflammatory disease affecting the eye, ear, skin and meninges [1,2]. The diagnosis of VKH disease could be confusing before the appearance of typical ophthalmological symptoms. Focal neurological signs are rare in VKH disease [1,2], and urological symptoms have not yet been described. We report a patient with VKH disease who presented a rare syndrome, such as meningitis-retention syndrome. Furthermore, we discuss the difficulty in diagnosing this disease due to increased adenosine deaminase (ADA) levels in the cerebrospinal fluid (CSF). 2. Case report In December 2012, a 67-year-old man developed severe headache 14 days before his admission, followed by appetite loss and fever. Four days before admission, he developed urinary voiding difficulty and urinary retention on the following
∗ Corresponding author at: Department of Neurology, Chiba Rosai Hospital, 2-16 Tatsumidai-Higashi, Ichihara-shi, Chiba 290-0003, Japan. Tel.: +81 436 74 1111; fax: +81 436 74 1151. E-mail address: [email protected] (A. Hiraga). http://dx.doi.org/10.1016/j.clineuro.2014.09.021 0303-8467/© 2014 Elsevier B.V. All rights reserved.
day and was therefore referred to the emergency room in our hospital. A Foley’s catheter was placed into his bladder. He was then admitted in the urology department. On admission, his body temperature was 37.6 ◦ C. Peripheral white blood cell count and haemoglobin 8200/L and 17.1 g/dL, respectively. Blood chemistry results revealed 25 IU/L of aspartate aminotransferase, 24 IU/L of alanine aminotransferase and 0.1 mg/dL of serum C-reactive protein. Although urinalysis showed no pathogen or white blood cells, urinary retention and fever seemed to be caused by urinary tract infection. An intravenous antibiotic therapy was initiated, but his symptoms did not ameliorate. Therefore, he was referred to the neurology department seven days after admission. During the initial neurological examination, he was alert and co-operative with no neck stiffness or Kernig’s sign. His pupils were equal with no limitation in the eye movements. Moreover, he had no facial-nerve palsy. His speech, muscle strength in the extremities, co-ordination, and sensory system were normal. CSF analysis revealed 75 white blood cells/mm3 (6% neutrophils and 94% lymphocytes), a glucose level of 77 mg/dL (simultaneous blood sugar 178 mg/dL) and a protein level of 81 mg/dL. Polymerase chain reaction analysis of CSF was negative for tuberculosis. CSF cultures and cytological CSF examination showed no pathogens and negativity for the CSF cryptococcal antigen. We subsequently found that the CSF ADA levels increased to 12.9 U/L, and CSF viral titres were negative. Cranial computed tomography showed no intracranial abnormality.
A. Hiraga et al. / Clinical Neurology and Neurosurgery 127 (2014) 42–43
Fig. 1. Fluorescein angiography of the right eye analysed 36 days after the onset of neurological symptoms. It reveals disclosed and multiple choroidal leakage and mild disc hyperfluorescence.
His clinical history, physical examination and elevated CSF lymphocytes were consistent with the diagnosis of aseptic meningitis (meningitis-retention syndrome). However, conservative therapy did not improve his symptoms. On the 16th day after admission, the pleocytosis was practically unchanged (85/mm3 ) in the second CSF samples, and the glucose levels decreased to 58 mg/dL (blood sugar 159 mg/dL), which was incompatible with the aseptic meningitis. We suspected tuberculous meningitis, and oral isoniazid, rifampicin and pyrazinamide were initially administered 16 days after admission. However, his symptoms did not ameliorate, and the patient noticed a perception of floaters in the left eye 20 days after admission. Ophthalmological examination on 23 days after admission showed that the visual acuity was 1.0 in the right eye and 0.7 in the left eye. Fundus examination revealed optic disc hyperaemia in both eyes. In a slit-lamp examination, no anterior chamber cells were observed, but keratic precipitates were found. Fluorescein angiography revealed optic nerve staining and multiple choroidal leakages in both eyes (Fig. 1). VKH disease was diagnosed, and methylprednisolone (1 g per day for 3 days) was intravenously administered from the 23rd day after admission. Marked clinical improvements were observed within a day after the initiation of corticosteroid therapy, which dramatically resolved headache, appetite loss and visual symptoms. CSF pleocytosis and ADA levels recovered in parallel with his clinical symptoms. The patient was discharged 2 months after admission.
43
phase, the acute ocular or uveitic phase begins [1,2]. However, the patient showed uveitic phase 34 days after the onset of headache, making the early diagnosis of VKH disease difficult. Elderly patients (65 years and over) with VKH disease have become more frequent in recent years [3]. Therefore, neurologists should include VKH disease in the differential diagnosis for etiologically undiagnosed meningitis in elderly patients. No case of VKH disease with meningitis-retention syndrome has been previously reported. However, combination of acute urinary retention and aseptic meningitis was reported as a case of meningitis-retention syndrome [4]. Typical symptoms of meningitis-retention syndrome are fever, headache and stiff neck with/without minor pyramidal signs together with acute urinary retention. Because meningitis-retention syndrome has a benign and self-remitting course [4], we preliminarily selected conservative therapies during the initial neurological examination. Meningitis-retention syndrome seemed to be an extremely mild form of acute disseminated encephalomyelopathy, and the lesion site of meningitis-retention syndrome has been suggested to be at the spinal cord. Because the patient had no other neurological symptoms suggesting spinal cord involvement and urodynamic studies were not performed, the underlying mechanism of meningitis-retention syndrome in VKH disease was unclear. However, our case suggests that VKH disease can present urinary retention presumably due to the spinal cord involvement. Another major concern was the increased CSF ADA levels. The CSF ADA estimation seemed to be useful in the diagnosis of tuberculous meningitis. Although non-tuberculous infectious meningitis, such as pyogenic meningitis, could elevate the CSF ADA levels, noninfectious neurologic diseases commonly could not elevate it [5]. However, clinical features of CSF in our patient did not show any evidence which indicates infectious meningitis. In conclusion, VKH disease should be listed in the differential diagnosis of meningitis-retention syndrome, which may precede uveitis in this inflammatory disorder. Moreover, it may present as an acute or subacute lymphocytic meningitis with increased CSF ADA and glucose consumption in CSF. Although these results indicate that the CSF ADA levels are not helpful to differentiate VKH disease from tuberculous meningitis, the differential diagnosis was extremely important because therapeutic strategies of VKH disease differ from aseptic or tuberculous meningitis. Conflict of interest We have no conflicts of interest. References
3. Discussion Our patient was diagnosed with VKH disease because of the combination of uveitis (appeared later) and meningitis. Furthermore, the patient was unique due to meningitis-retention syndrome and increased CSF ADA levels, both of which completely disappeared after corticosteroid therapy. Uveitis appeared 34 days after the onset of neurological symptoms. In general, VKH disease evolves in four phases: (1) prodromal, (2) uveitic, (3) convalescent and (4) chronic/recurrent. In the prodromal phase, patients develop headache and fever. From 3 days to 2 weeks after the prodromal
[1] Andreoli CM, Foster CS. Vogt–Koyanagi–Harada disease. Int Ophthalmol Clin 2006;46:111–22. [2] Pan D, Hirose T. Vogt–Koyanagi–Harada syndrome: review of clinical features. Semin Ophthalmol 2011;26:312–5. [3] Kiyomoto C, Imaizumi M, Kimoto K, Abe H, Nakano S, Nakatsuka K. Vogt–Koyanagi–Harada disease in elderly Japanese patients. Int Ophthalmol 2007;27:149–53. [4] Sakakibara R, Kishi M, Tsuyusaki Y, Tateno A, Tateno F, Uchiyama T, et al. “Meningitis-retention syndrome”: a review. Neurourol Urodyn 2013;32: 19–23. [5] Sun Q, Sha W, Xiao HP, Tian Q, Zhu H. Evaluation of cerebrospinal fluid adenosine deaminase activity for the differential diagnosis of tuberculous and nontuberculous meningitis. Am J Med Sci 2012;344:116–21.
