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Ocular flutter and ataxia without cognitive impairment associated with steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT)
Journal of the Neurological Sciences 359 (2015) 86–87
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Ocular flutter and ataxia without cognitive impairment associated with steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) Keywords: Antithyroid antibody Autoimmune encephalopathy Steroid-responsive encephalopathy associated with autoimmune thyroiditis Hashimoto encephalopathy Ocular flutter Ataxia
Dear sir, Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), often called Hashimoto's encephalopathy, is a disorder that comprises a heterogeneous group of neurological symptoms that manifests in patients with high titers of antithyroid antibodies [1]. The most common symptoms are cognitive impairment and seizure, followed by behavioral disorder, myoclonus, gait ataxia, dysphasia/aphasia, confusion, tremor, psychosis, headache, sleep disorders, motor deficit, hyperreflexia, depression, wordfinding difficulty, and visual changes [2]. Opsoclonus with encephalopathy was rarely found in those patients [3,4], however, ocular flutter has not been reported. A previously healthy 30-year-old man was admitted with ataxia in all four limbs and gait disturbance that had deteriorated over the previous four days. His orientation, memory and language were intact. He was suffering intermittent bursts of horizontal ocular flutter, which was usually induced by a gaze shift (Video 1). Opsoclonus was not observed during the illness. Mild dysarthria, ataxia and occasional myoclonus in his trunk and limbs, and truncal titubation were noted. Magnetic resonance imaging of the brain, routine cerebrospinal fluid (CSF) analysis, electroencephalography, electromyography, nerve conduction studies, and somatosensory evoked potentials were all unremarkable. Serologic tests, cultures, and polymerase chain reactions performed on blood and CSF were negative for viral, bacterial, and fungal infections. Serological tests were also negative for rheumatoid factor, anti-nuclear antibody (Ab), anti-dsDNA, anti-Sjögren's syndrome A/B, anti-neutrophil cytoplasmic Ab, anti-phospholipid Ab, anti-cardiolipin Ab, anti-Hu, anti-Yo, anti-Ri, anti-Ma2, collapsin response mediator protein 4/5, amphiphysin, recoverin, sex determining region Y-box 1, titin, N-methyl-D-aspartate receptor, alpha-amino-3hydroxy-5-methylisoxazole-4-propionic acid 1/2, leucine-rich gliomainactivated 1, contactin-associated protein 2, γ-Aminobutyric acid-B receptor, anti-ganglioside (anti-GM1, GD1b, myelin associated glycoprotein) Ab, and the IgG and IgM Abs against GQ1b.
http://dx.doi.org/10.1016/j.jns.2015.10.037 0022-510X/© 2015 Elsevier B.V. All rights reserved.
The concentration of anti-thyroglobulin Ab was markedly increased (398 U/mL, normal range b 115 U/mL) with a euthyroid state. Levels of anti-microsomal Ab and anti-thyroid peroxidase Ab were within the normal range. Treatment with intravenous methylprednisolone (1 g/day) was performed for five days, followed by oral prednisolone, which resulted in a marked improvement of his symptoms. The dose of oral prednisolone was started at 60 mg/day and gradually reduced to 20 mg/day for the following 20 days and maintained for one month, and at 10 mg/day for the following nine months. One month after starting the treatment with steroid, the patient was only suffering mild ocular flutter, and the serum level of anti-thyroglobulin Ab had reduced to a normal range (108 U/mL). Three months later, all his symptoms had resolved completely. Our case was not typical for SREAT because the patient did not show any cognitive impairment; however, his condition fulfilled the remaining criteria previously used [5]. Considering the incidence of increased anti-thyroglobulin Ab is more than 10% in general population [6], it could be a coincidence of anti-thyroglobulin Ab increment and a steroid-responsive central nervous system (CNS)-involving disorder which we cannot identify yet. However, we performed all available tests to rule out other possible causes, which were negative. For now, it could be more appropriate to consider that the symptoms were the manifestations of the condition associated with increased antithyroglobulin Ab. Furthermore, Whipple's disease with CNS involvement cannot be completely ruled out; however, to the best of our knowledge, it has not been reported in Korea. In addition, the patient did not show other symptoms suggesting the disease and recovered without treatment with antibiotics. The etiology of SREAT remains unknown, although possible pathogenic mechanisms include autoimmune reaction to antigens shared by the thyroid gland and central nervous system, autoimmune vasculitis, and toxic effects of thyrotropin-releasing hormone [1]. Ocular flutter is defined by intermittent bursts of involuntary conjugate eye oscillations with a strict preponderance for the horizontal plane and without an intersaccadic interval [7]. It is associated with a wide variety of conditions, including infections, medications and paraneoplastic syndromes [8]. Recently, a patient presenting ocular flutter with increased anti-thyroglobulin Ab and anti-thyroid peroxidase Ab was reported in Korea, however, antibodies for autoimmune encephalitis or paraneoplastic disease were not assessed [9]. The pathophysiology of ocular flutter is thought to arise from dysfunction of the brainstem and/or cerebellum [9]. It is assumed that abnormal Purkinje cell activity in the cerebellum leads to reduced inhibition on the fastigial nucleus, which results in a loss of omnipause neuron inhibition on burst neurons within the paramedian pontine reticular formation [7]. Generalized myoclonus observed in our patient most likely resulted from a dysfunction within the Guillain–Mollaret triangle between the nucleus ruber, the inferior olive, and the dentate nucleus of the cerebellum [10]. In conclusion, we have presented a patient with ocular flutter and ataxia, without cognitive impairment, as the presenting feature associated with elevated anti-thyroglobulin Ab in serum, who showed good
Letter to the Editor
response to steroid. Although it is rare, a patient who presents with ocular flutter with or without active thyroid disease, after excluding the main causes, should be tested for anti-thyroid antibodies, especially when accompanied by an atypical presentation. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.jns.2015.10.037. Disclosure statement
87
[6] J.G. Hollowell, N.W. Staehling, W.D. Flanders, et al., Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III), J. Clin. Endocrinol. Metab. 8 (2002) 489–499. [7] B. Gaymard, C. Pierrot, Neurology of saccades and smooth pursuit, Curr. Opin. Neurol. 12 (1999) 13–19. [8] L.J. Leigh, D.S. Zee, The neurology of eye movements, 3rd edn. Oxford University Press, New York, 1999 133–144. [9] H.C. Kim, S.E. Kim, J. Lee, et al., Hashimoto's encephalopathy presenting with ocular flutter, J. Korean Neurol. Assoc. 33 (2015) 100–102. [10] J. Lemos, E. Eggenberger, Saccadic intrusions: review and update, Curr. Opin. Neurol. 26 (2013) 59–66.
The authors have no conflicts of interest to disclose. Ethical standard All human study must state that have been approved by the appropriate ethics committee and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. References [1] N. Schiess, C.A. Pardo, Hashimoto's encephalopathy, Ann. N. Y. Acad. Sci. 1142 (2008) 254–265. [2] N.C. de Holanda, D.D. de Lima, T.B. Cavalcanti, C.S. Lucena, F. Bandeira, Hashimoto's encephalopathy: systematic review of the literature and an additional case, J. Neuropsychiatry Clin. Neurosci. 23 (2011) 384–390. [3] R. Salazar, C. Mehta, N. Zaher, D. Miller, Opsoclonus as a manifestation of Hashimoto's encephalopathy, J. Clin. Neurosci. 19 (2012) 1465–1466. [4] E.L.E. Hernández, A. Saiz, F. Graus, et al., Detection of 14–3-3 protein in the CSF of a patient with Hashimoto's encephalopathy, Neurology 54 (2000) 1539–1540. [5] P. Castillo, B. Woodruff, R. Caselli, et al., Steroid-responsive encephalopathy associated with autoimmune thyroiditis, Arch. Neurol. 63 (2006) 197–202.
Hyun Jo Lee Kipyoung Jeon Jong Yoon Lee Jee Eun Lee Dae Woong Bae Yoon Sang Oh A-Hyun Cho Woojun Kim⁎ Department of Neurology, The Catholic University of Korea, College of Medicine, Seoul, South Korea ⁎Corresponding author at: Department of Neurology, The Catholic University of Korea, College of Medicine, 222 Banpodae-ro, Seocho-gu, Seoul, South Korea E-mail address: [email protected]. 21 August 2015
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Ocular flutter and ataxia without cognitive impairment associated with steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) Keywords: Antithyroid antibody Autoimmune encephalopathy Steroid-responsive encephalopathy associated with autoimmune thyroiditis Hashimoto encephalopathy Ocular flutter Ataxia
Dear sir, Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), often called Hashimoto's encephalopathy, is a disorder that comprises a heterogeneous group of neurological symptoms that manifests in patients with high titers of antithyroid antibodies [1]. The most common symptoms are cognitive impairment and seizure, followed by behavioral disorder, myoclonus, gait ataxia, dysphasia/aphasia, confusion, tremor, psychosis, headache, sleep disorders, motor deficit, hyperreflexia, depression, wordfinding difficulty, and visual changes [2]. Opsoclonus with encephalopathy was rarely found in those patients [3,4], however, ocular flutter has not been reported. A previously healthy 30-year-old man was admitted with ataxia in all four limbs and gait disturbance that had deteriorated over the previous four days. His orientation, memory and language were intact. He was suffering intermittent bursts of horizontal ocular flutter, which was usually induced by a gaze shift (Video 1). Opsoclonus was not observed during the illness. Mild dysarthria, ataxia and occasional myoclonus in his trunk and limbs, and truncal titubation were noted. Magnetic resonance imaging of the brain, routine cerebrospinal fluid (CSF) analysis, electroencephalography, electromyography, nerve conduction studies, and somatosensory evoked potentials were all unremarkable. Serologic tests, cultures, and polymerase chain reactions performed on blood and CSF were negative for viral, bacterial, and fungal infections. Serological tests were also negative for rheumatoid factor, anti-nuclear antibody (Ab), anti-dsDNA, anti-Sjögren's syndrome A/B, anti-neutrophil cytoplasmic Ab, anti-phospholipid Ab, anti-cardiolipin Ab, anti-Hu, anti-Yo, anti-Ri, anti-Ma2, collapsin response mediator protein 4/5, amphiphysin, recoverin, sex determining region Y-box 1, titin, N-methyl-D-aspartate receptor, alpha-amino-3hydroxy-5-methylisoxazole-4-propionic acid 1/2, leucine-rich gliomainactivated 1, contactin-associated protein 2, γ-Aminobutyric acid-B receptor, anti-ganglioside (anti-GM1, GD1b, myelin associated glycoprotein) Ab, and the IgG and IgM Abs against GQ1b.
http://dx.doi.org/10.1016/j.jns.2015.10.037 0022-510X/© 2015 Elsevier B.V. All rights reserved.
The concentration of anti-thyroglobulin Ab was markedly increased (398 U/mL, normal range b 115 U/mL) with a euthyroid state. Levels of anti-microsomal Ab and anti-thyroid peroxidase Ab were within the normal range. Treatment with intravenous methylprednisolone (1 g/day) was performed for five days, followed by oral prednisolone, which resulted in a marked improvement of his symptoms. The dose of oral prednisolone was started at 60 mg/day and gradually reduced to 20 mg/day for the following 20 days and maintained for one month, and at 10 mg/day for the following nine months. One month after starting the treatment with steroid, the patient was only suffering mild ocular flutter, and the serum level of anti-thyroglobulin Ab had reduced to a normal range (108 U/mL). Three months later, all his symptoms had resolved completely. Our case was not typical for SREAT because the patient did not show any cognitive impairment; however, his condition fulfilled the remaining criteria previously used [5]. Considering the incidence of increased anti-thyroglobulin Ab is more than 10% in general population [6], it could be a coincidence of anti-thyroglobulin Ab increment and a steroid-responsive central nervous system (CNS)-involving disorder which we cannot identify yet. However, we performed all available tests to rule out other possible causes, which were negative. For now, it could be more appropriate to consider that the symptoms were the manifestations of the condition associated with increased antithyroglobulin Ab. Furthermore, Whipple's disease with CNS involvement cannot be completely ruled out; however, to the best of our knowledge, it has not been reported in Korea. In addition, the patient did not show other symptoms suggesting the disease and recovered without treatment with antibiotics. The etiology of SREAT remains unknown, although possible pathogenic mechanisms include autoimmune reaction to antigens shared by the thyroid gland and central nervous system, autoimmune vasculitis, and toxic effects of thyrotropin-releasing hormone [1]. Ocular flutter is defined by intermittent bursts of involuntary conjugate eye oscillations with a strict preponderance for the horizontal plane and without an intersaccadic interval [7]. It is associated with a wide variety of conditions, including infections, medications and paraneoplastic syndromes [8]. Recently, a patient presenting ocular flutter with increased anti-thyroglobulin Ab and anti-thyroid peroxidase Ab was reported in Korea, however, antibodies for autoimmune encephalitis or paraneoplastic disease were not assessed [9]. The pathophysiology of ocular flutter is thought to arise from dysfunction of the brainstem and/or cerebellum [9]. It is assumed that abnormal Purkinje cell activity in the cerebellum leads to reduced inhibition on the fastigial nucleus, which results in a loss of omnipause neuron inhibition on burst neurons within the paramedian pontine reticular formation [7]. Generalized myoclonus observed in our patient most likely resulted from a dysfunction within the Guillain–Mollaret triangle between the nucleus ruber, the inferior olive, and the dentate nucleus of the cerebellum [10]. In conclusion, we have presented a patient with ocular flutter and ataxia, without cognitive impairment, as the presenting feature associated with elevated anti-thyroglobulin Ab in serum, who showed good
Letter to the Editor
response to steroid. Although it is rare, a patient who presents with ocular flutter with or without active thyroid disease, after excluding the main causes, should be tested for anti-thyroid antibodies, especially when accompanied by an atypical presentation. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.jns.2015.10.037. Disclosure statement
87
[6] J.G. Hollowell, N.W. Staehling, W.D. Flanders, et al., Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III), J. Clin. Endocrinol. Metab. 8 (2002) 489–499. [7] B. Gaymard, C. Pierrot, Neurology of saccades and smooth pursuit, Curr. Opin. Neurol. 12 (1999) 13–19. [8] L.J. Leigh, D.S. Zee, The neurology of eye movements, 3rd edn. Oxford University Press, New York, 1999 133–144. [9] H.C. Kim, S.E. Kim, J. Lee, et al., Hashimoto's encephalopathy presenting with ocular flutter, J. Korean Neurol. Assoc. 33 (2015) 100–102. [10] J. Lemos, E. Eggenberger, Saccadic intrusions: review and update, Curr. Opin. Neurol. 26 (2013) 59–66.
The authors have no conflicts of interest to disclose. Ethical standard All human study must state that have been approved by the appropriate ethics committee and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. References [1] N. Schiess, C.A. Pardo, Hashimoto's encephalopathy, Ann. N. Y. Acad. Sci. 1142 (2008) 254–265. [2] N.C. de Holanda, D.D. de Lima, T.B. Cavalcanti, C.S. Lucena, F. Bandeira, Hashimoto's encephalopathy: systematic review of the literature and an additional case, J. Neuropsychiatry Clin. Neurosci. 23 (2011) 384–390. [3] R. Salazar, C. Mehta, N. Zaher, D. Miller, Opsoclonus as a manifestation of Hashimoto's encephalopathy, J. Clin. Neurosci. 19 (2012) 1465–1466. [4] E.L.E. Hernández, A. Saiz, F. Graus, et al., Detection of 14–3-3 protein in the CSF of a patient with Hashimoto's encephalopathy, Neurology 54 (2000) 1539–1540. [5] P. Castillo, B. Woodruff, R. Caselli, et al., Steroid-responsive encephalopathy associated with autoimmune thyroiditis, Arch. Neurol. 63 (2006) 197–202.
Hyun Jo Lee Kipyoung Jeon Jong Yoon Lee Jee Eun Lee Dae Woong Bae Yoon Sang Oh A-Hyun Cho Woojun Kim⁎ Department of Neurology, The Catholic University of Korea, College of Medicine, Seoul, South Korea ⁎Corresponding author at: Department of Neurology, The Catholic University of Korea, College of Medicine, 222 Banpodae-ro, Seocho-gu, Seoul, South Korea E-mail address: [email protected]. 21 August 2015