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Elevated titers of anti-thyroperoxidase antibodies in patients with multiple system atrophy: A pilot study
Clinical Neurology and Neurosurgery 115 (2013) 2348–2350
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Elevated titers of anti-thyroperoxidase antibodies in patients with multiple system atrophy: A pilot study Boris Shihman a , Nir Giladi b , Margalit Bleiberg c , Alina Rosenberg d , Amos D. Korczyn b , Tanya Gurevich b,∗ a
Department of Neurology, Rabin Medical Center, Petah-Tiqva, Israel Parkinson’s Disease and Neuroautonomic Service, Movement Disorders Unit, Department of Neurology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel c Clinical Immunology Laboratory, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel d School of Health Professions, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel b
a r t i c l e
i n f o
Article history: Received 5 February 2012 Received in revised form 28 July 2013 Accepted 12 August 2013 Available online 21 September 2013 Keywords: Multiple system atrophy Autoimmune mechanisms Antithyroperoxidase antibodies Parkinson’s disease Cerebellar syndrome
a b s t r a c t Objectives: Multiple system atrophy (MSA) is a neurodegenerative disease characterized by progressive neuronal loss and alpha-synuclein deposition in oligodendroglial cells in the central nervous system. The cause of MSA remains essentially unknown. A cerebellar syndrome was associated with autoimmune thyroid disease in some cases, apparently not related to MSA and was partially responsive to immunomodulatory therapy. Patients and methods: 28 euthyroid patients who fulfilled the diagnostic criteria for probable MSA, 11 with MSA-cerebellar type (MSA-C), 17 with MSA-parkinsonian type (MSA-P), 28 patients with Parkinson’s disease (PD) and 26 normal euthyroid controls were tested the for serum levels of anti-thyroperoxidase antibodies (anti-TPO) and anti-thyroglobulin (Anti-TG) antibodies (Ab). Results: The laboratory results were statistically similar in all three groups, but 3 MSA-C patients had highly elevated anti-TPO Ab titers. Conclusion: We identified the presence of elevated anti-TPO levels in a small subgroup of MSA-C patients but neither in MSA-P or PD patients nor in healthy controls. These findings may suggest an autoimmune etiology in some cases of MSA-C. © 2013 Elsevier B.V. All rights reserved.
1. Introduction Multiple system atrophy (MSA) is a rare adult-onset neurodegenerative disease characterized by progressive neuronal loss and alpha-synuclein deposition in oligodendroglial cells in numerous sites in the central nervous system [1,2]. The incidence of the disease is estimated to be 0.6 cases per 100.000 person-years, while the prevalence is between 1.9–4.9 cases per 100.000 population [3]. Clinically, the cardinal features include autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. According to consensus criteria, patients with MSA are clinically classified according to the predominant motor presentation into cerebellar (MSA-C) and parkinsonian (MSA-P) subtypes. No evidence for a genetic etiology has been found and the cause of MSA remains essentially unknown. No currently available therapy can reverse or halt progression of the disease. Autoimmune mechanisms and toxic agents have been suggested as potential causes of MSA, but evidence for these etiologies is weak [4,5]. A
∗ Corresponding author. Tel.: +972 3 6974912; fax: +972 3 6974911. E-mail address: [email protected] (T. Gurevich). 0303-8467/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2013.08.013
higher prevalence of Hashimoto’s thyroiditis has been found in female patients with multiple sclerosis, a neurodegenerative disease with suspected autoimmune mechanisms, which also affect oligodendrocytes [6]. A cerebellar syndrome was associated with autoimmune thyroid disease in some cases, and was partially responsive to immunomodulatory therapy [7,8]. Blanchin et al. [9] demonstrated that anti-thyroid antibodies from patients with Hashimoto’s encephalopathy may bind to cerebellar astrocytes in monkeys. In the general population the prevalence of positive antithyroperoxidase antibodies (anti-TPO) reached about 12% according to a recent Chinese study [10]. In the present pilot study, we evaluated the possibility of thyroid autoimmunity as a contributor to MSA. 2. Methods 2.1. Subjects Serum levels of anti-thyroperoxidase (anti-TPO) anti-TPO Ab and anti-thyroglobulin (Anti-TG) antibodies (Ab) were measured in 28 consecutive patients over 40 years of age who fulfilled the
B. Shihman et al. / Clinical Neurology and Neurosurgery 115 (2013) 2348–2350
2349
Table 1 Clinical characteristics of patients with probable Multiple System Atrophy (MSA), patients with Parkinson’s Disease (PD) and controls.
Females/males Age (years) Age at onset (years) Disease duration (years)
All MSA patients (n = 28)
MSA-P (n = 17)
MSA-C (n = 11)
MSA-C with normal Anti-TPO Ab levels (n = 8)
MSA-C with high Anti-TPO Ab levels (n = 3)
PD patients (n = 28)
Control s* (n = 26)
6/12 59.9 ± 10.6 54.0 ± 11.5 5.6 ± 3.3
10/7 62.3 ± 11.2 55.7 ± 12.9 6.4 ± 3.6
6/5 54.0 ± 5.9 50.1 ± 6.4 3.9 ± 1.8
4/4 60.5 (range 51–71) 56.4 (range 50–68) 4.4 ± 2.4 (2–9)
2/1 53.3 (range 48–55) 57.0 (range 46–53) 2.7 (range 2–4)
9/19 67.1 ± 10.3 60.7 ± 13.9 9.4 ± 7.4
16/10 62.5 ± 13
* Normal euthyroid individuals. MSA-P: the MSA with the predominant motor presentation is parkinsonism; MSA-C: the MSA with the predominant motor presentation is cerebellar; Anti-TPO Ab: Antithyroperoxidase antibodies; Anti-TG Ab: Anti-thyroglobulin antibodies.
diagnostic criteria for probable MSA [1] (17 patients with MSAP and 11 with MSA-C, mean age 59.9 ± 10.6 years), 28 age- and gender-matched patients diagnosed as having Parkinson’s disease (PD) and 26 normal euthyroid controls. None of the participants had a history of thyroid disease. The clinical characteristics of the patients are presented in Table 1.
4. Results
Blood samples were assessed for anti-TPO Ab and anti-TG Ab levels by human anti-TPO and anti-TG enzyme immunoassay in the Clinical Immunology Laboratory of the Tel Aviv Medical Center. The normal values are <50 IU/ML for anti-TPO Ab and <100 IU/ML for anti-TG. The study was approved by the institutional review board. All patients signed informed consent forms.
All patients had normal thyroid function tests and did not take medications affecting the function of the thyroid gland. Anti-TPO Ab levels were remarkably elevated in three of the 11 MSA-C patients (27.3%) whose test values were 352.6 U/ml, 713.6 U/ml and 884.6 U/ml, respectively. After excluding these three cases, the mean value for the remaining 8 MSA-C patients was within overall normal ranges. Anti-TPO Ab were also high in one PD patient (247.6 U/ml) and in one control subject (227.4 U/ml), with an average value within normal range for these groups (Table 1 and Fig. 1). Disease duration until the test in 3 MSA-C patients with high titers of anti-TPO Ab had tendency to be shorter than in the other groups. Besides that, their clinical manifestations, age and age of the disease onset did not differ from the other patients (Table 2).
3. Statistical analysis
5. Discussion
Descriptive statistics for all measured variables include summary measures (means, standard deviations (SD), medians, percentiles and ranges of descriptive variables were generated as appropriate), and box plots in excel 2007. The Kruskal–Wallis test was used to examine overall differences between the groups. For pairwise comparisons the Mann–Whitney test was used. All statistical analyses were performed using SPSS 21.
Steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT), previously called Hashimoto encephalopathy is a term used to describe a type of encephalopathy of presumed autoimmune origin characterized by high titers of antiTPO Ab [11]. Moreover, in immunofluorescence assays on monkey brain cerebellum sections, both the sera and anti-TPO monoclonal antibodies of a patient with SREAT were able to bind to cerebellar cells expressing glial fibrillary acid protein [11]. Schott and Warren
2.2. Protocol
900 800 700
500
MSA-C
400
cont
300
MSA-P
An-TPO Ab, IU/ml
600
PD
200 100
50 0
PD
MSA-P
MSA-C
cont
MSA-P, the MSA with the predominant motor presentation is parkinsonism; MSA-C, the MSA with the predominant motor presentation is cerebellar; cont, controls; Anti-TPO Ab, Anti-thyroperoxidase antibodies levels, IU/ml; Fig. 1. Antibody levels in the patients and controls. MSA-P: the MSA with the predominant motor presentation is parkinsonism; MSA-C: the MSA with the predominant motor presentation is cerebellar; cont: controls; Anti-TPO Ab: Anti-thyroperoxidase antibodies levels, IU/ml.
2350
B. Shihman et al. / Clinical Neurology and Neurosurgery 115 (2013) 2348–2350
Table 2 Antibody levels in the study patients and controls. MSA-P patients
MSA-C all patients
MSA-C with normal Anti-TPO Ab levels
MSA-C with high Anti-TPO Ab levels
PD patients
Controls*
No. of patients Anti-TPO Ab levels, IU/ml median (IQR)
17 6.4 ± 1.4
11 21.9 ± 6.4
8 13.5 ± 11.6
28 13.0 ± 9. 3
26 11.5 ± 9. 2
Anti-TG Ab levels, IU/ml median (IQR)
7.8 ± 1, 8
47.1 ± 15.3
41.1 ± 42.4
3 Parameters: 352.6 IU/ml 713.6 IU/ml 884.6 IU/ml Parameters: 75.6 IU/ml 139.8 IU/ml 60.7 IU/ml
38.5 ± 29. 7
38.5 ± 23. 9
IQR – interquartile range.
[12] suggested that SREAT should be viewed as a syndrome, but not as a diagnosis. Lee et al. [13] observed higher titers of anti-TG and anti-TPO Ab in their patients with MSA, compared with PD patients. Although ataxia correlated with anti-TG and anti-TPO antibodies, there was no significant difference in the frequency of abnormal titer between MSA-P and MSA-C groups in their study [13]. We identified the presence of elevated anti-TPO levels in our group of MSA-C patients but not in MSA-P or PD patients or in healthy controls. These findings may suggest an autoimmune component in some cases of MSA-C, that is different from the parkinsonian type of MSA, and associated with cerebellar damage. Similar findings were reported in other forms of cerebellar ataxia [14]. Since autopsy data are not available for any of our patients, it is unknown whether the pathology of the MSA-C cases with high anti TPO antibodies is identical to the remainder and contains the same oligodendrocyte changes. Elevated antithyroid antibodies are not rare in apparently normal aging, and a chance occurrence cannot be excluded. Therefore, study of additional MSA patients is required. This report describes a small number of cases. Furthermore, the lack of cerebrospinal fluid examinatioms, and the fact that immunomodulatory drugs have not been administered, limit any attempt to generalize. However, if confirmed, these observations may be significant. In conclusion, anti-TG Ab levels were within the normal range in all MSA patients. The demonstration of highly elevated titers of anti-TPO Ab in some MSA-C patients may support an autoimmune contribution to the pathogenesis of the syndrome. If confirmed, these novel data may have interesting clinical and therapeutic implications [15,16]. Acknowledgment Esther Eshkol is thanked for editorial assistance.
References [1] Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008;71(9):670–6. [2] Trojanowski J. Proposed neuropathological criteria for the postmortem diagnosis of multiple system atrophy. Neuropathol Appl Neurobiol 2007;33:615–20. [3] Vanacore N. Epidemiological evidence on multiple system atrophy. J Neural Transm 2005;112(12):1605–12. [4] Ozawa T. Pathology and genetics of multiple system atrophy: an approach to determining genetic susceptibility spectrum. Acta Neuropathol 2006;112(5):531–8. [5] Manto MU. Hashimoto’s associated ataxia. J Neurol Neurosurg Psychiatry 2002;72(2):277–8. [6] Karni A, Abramsky O. Association of MS with thyroid disorders. Neurology 1999 Sep. [7] Selim M, Drachman DA. Ataxia associated with Hashimoto’s disease: progressive non-familial adult onset cerebellar degeneration with autoimmune thyroiditis. J Neurol Neurosurg Psychiatry 2001;71(1):81–7. [8] Passarella B, Negro C, Nozzoli C, De Marco V, Rini A. Cerebellar subacute syndrome due to corticosteroid-responsive encephalopathy associated with autoimmune thyroiditis (also called “Hashimoto’s encephalopathy”). Clin Ter 2005;156(1–2):13–7. [9] Blanchin S, Coffin C, Viader F, Ruf J, Carayon P, Potier F, et al. Antithyroperoxidase antibodies from patients with Hashimoto’s encephalopathy bind to cerebellar astrocytes. J Neuroimmunol 2007;192(1–2):13–20. [10] Li Y, Teng D, Shan Z, Teng X, Guan H, Yu X, et al. Antithyroperoxidase and.antibodies in a five-year follow-up survey of populations with different iodine intakes. J Clin Endocrinol Metab 2008;93(5):1751–7. [11] Mocellin R, Walerfang M, Velakoulis D. Hashimoto’s encephalopathy: epidemiology, pathogenesis and management. CNS Drugs 2007;21(10):799–811. [12] Schott JM, Warren JD. Steroid responsive encephalopathy with positive thyroid antibodies. A syndrome, not a diagnosis? J Neurol 2007;254(4):542. [13] Lee-WE, Lee TJ, Oh SM, Yoon WT, Cho J, Ahn J, et al. Analysis of serum antithyroid antibodies titers in Parkinson’s Disease and multiple system atrophy. Parkinsonism Relat Disord 2009;15S2:S57. [14] Hadjivassiliou M, Boscolo S, Tongiorgi E, Grünewald RA, Sharrack B, Sanders DS, et al. Cerebellar ataxia as a possible organ-specific autoimmune disease. Mov Disor 2008;23(10):1370–7. [15] Nanri K, Okita M, Takeguchi M, Taguchi T, Ishoko T, Saito H, et al. Intravenous immunoglobulin therapy for autoantibody-positive cerebellar ataxia. Intern Med 2009;48(10):783–90. [16] Novak P, Williams A, Ravin P, Zurkiya O, Abduljalil A, Novak V. Treatment of multiple system atrophy using intravenous immunoglobulin. BMC Neurol 2012;12:131.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Elevated titers of anti-thyroperoxidase antibodies in patients with multiple system atrophy: A pilot study Boris Shihman a , Nir Giladi b , Margalit Bleiberg c , Alina Rosenberg d , Amos D. Korczyn b , Tanya Gurevich b,∗ a
Department of Neurology, Rabin Medical Center, Petah-Tiqva, Israel Parkinson’s Disease and Neuroautonomic Service, Movement Disorders Unit, Department of Neurology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel c Clinical Immunology Laboratory, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel d School of Health Professions, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel b
a r t i c l e
i n f o
Article history: Received 5 February 2012 Received in revised form 28 July 2013 Accepted 12 August 2013 Available online 21 September 2013 Keywords: Multiple system atrophy Autoimmune mechanisms Antithyroperoxidase antibodies Parkinson’s disease Cerebellar syndrome
a b s t r a c t Objectives: Multiple system atrophy (MSA) is a neurodegenerative disease characterized by progressive neuronal loss and alpha-synuclein deposition in oligodendroglial cells in the central nervous system. The cause of MSA remains essentially unknown. A cerebellar syndrome was associated with autoimmune thyroid disease in some cases, apparently not related to MSA and was partially responsive to immunomodulatory therapy. Patients and methods: 28 euthyroid patients who fulfilled the diagnostic criteria for probable MSA, 11 with MSA-cerebellar type (MSA-C), 17 with MSA-parkinsonian type (MSA-P), 28 patients with Parkinson’s disease (PD) and 26 normal euthyroid controls were tested the for serum levels of anti-thyroperoxidase antibodies (anti-TPO) and anti-thyroglobulin (Anti-TG) antibodies (Ab). Results: The laboratory results were statistically similar in all three groups, but 3 MSA-C patients had highly elevated anti-TPO Ab titers. Conclusion: We identified the presence of elevated anti-TPO levels in a small subgroup of MSA-C patients but neither in MSA-P or PD patients nor in healthy controls. These findings may suggest an autoimmune etiology in some cases of MSA-C. © 2013 Elsevier B.V. All rights reserved.
1. Introduction Multiple system atrophy (MSA) is a rare adult-onset neurodegenerative disease characterized by progressive neuronal loss and alpha-synuclein deposition in oligodendroglial cells in numerous sites in the central nervous system [1,2]. The incidence of the disease is estimated to be 0.6 cases per 100.000 person-years, while the prevalence is between 1.9–4.9 cases per 100.000 population [3]. Clinically, the cardinal features include autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. According to consensus criteria, patients with MSA are clinically classified according to the predominant motor presentation into cerebellar (MSA-C) and parkinsonian (MSA-P) subtypes. No evidence for a genetic etiology has been found and the cause of MSA remains essentially unknown. No currently available therapy can reverse or halt progression of the disease. Autoimmune mechanisms and toxic agents have been suggested as potential causes of MSA, but evidence for these etiologies is weak [4,5]. A
∗ Corresponding author. Tel.: +972 3 6974912; fax: +972 3 6974911. E-mail address: [email protected] (T. Gurevich). 0303-8467/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2013.08.013
higher prevalence of Hashimoto’s thyroiditis has been found in female patients with multiple sclerosis, a neurodegenerative disease with suspected autoimmune mechanisms, which also affect oligodendrocytes [6]. A cerebellar syndrome was associated with autoimmune thyroid disease in some cases, and was partially responsive to immunomodulatory therapy [7,8]. Blanchin et al. [9] demonstrated that anti-thyroid antibodies from patients with Hashimoto’s encephalopathy may bind to cerebellar astrocytes in monkeys. In the general population the prevalence of positive antithyroperoxidase antibodies (anti-TPO) reached about 12% according to a recent Chinese study [10]. In the present pilot study, we evaluated the possibility of thyroid autoimmunity as a contributor to MSA. 2. Methods 2.1. Subjects Serum levels of anti-thyroperoxidase (anti-TPO) anti-TPO Ab and anti-thyroglobulin (Anti-TG) antibodies (Ab) were measured in 28 consecutive patients over 40 years of age who fulfilled the
B. Shihman et al. / Clinical Neurology and Neurosurgery 115 (2013) 2348–2350
2349
Table 1 Clinical characteristics of patients with probable Multiple System Atrophy (MSA), patients with Parkinson’s Disease (PD) and controls.
Females/males Age (years) Age at onset (years) Disease duration (years)
All MSA patients (n = 28)
MSA-P (n = 17)
MSA-C (n = 11)
MSA-C with normal Anti-TPO Ab levels (n = 8)
MSA-C with high Anti-TPO Ab levels (n = 3)
PD patients (n = 28)
Control s* (n = 26)
6/12 59.9 ± 10.6 54.0 ± 11.5 5.6 ± 3.3
10/7 62.3 ± 11.2 55.7 ± 12.9 6.4 ± 3.6
6/5 54.0 ± 5.9 50.1 ± 6.4 3.9 ± 1.8
4/4 60.5 (range 51–71) 56.4 (range 50–68) 4.4 ± 2.4 (2–9)
2/1 53.3 (range 48–55) 57.0 (range 46–53) 2.7 (range 2–4)
9/19 67.1 ± 10.3 60.7 ± 13.9 9.4 ± 7.4
16/10 62.5 ± 13
* Normal euthyroid individuals. MSA-P: the MSA with the predominant motor presentation is parkinsonism; MSA-C: the MSA with the predominant motor presentation is cerebellar; Anti-TPO Ab: Antithyroperoxidase antibodies; Anti-TG Ab: Anti-thyroglobulin antibodies.
diagnostic criteria for probable MSA [1] (17 patients with MSAP and 11 with MSA-C, mean age 59.9 ± 10.6 years), 28 age- and gender-matched patients diagnosed as having Parkinson’s disease (PD) and 26 normal euthyroid controls. None of the participants had a history of thyroid disease. The clinical characteristics of the patients are presented in Table 1.
4. Results
Blood samples were assessed for anti-TPO Ab and anti-TG Ab levels by human anti-TPO and anti-TG enzyme immunoassay in the Clinical Immunology Laboratory of the Tel Aviv Medical Center. The normal values are <50 IU/ML for anti-TPO Ab and <100 IU/ML for anti-TG. The study was approved by the institutional review board. All patients signed informed consent forms.
All patients had normal thyroid function tests and did not take medications affecting the function of the thyroid gland. Anti-TPO Ab levels were remarkably elevated in three of the 11 MSA-C patients (27.3%) whose test values were 352.6 U/ml, 713.6 U/ml and 884.6 U/ml, respectively. After excluding these three cases, the mean value for the remaining 8 MSA-C patients was within overall normal ranges. Anti-TPO Ab were also high in one PD patient (247.6 U/ml) and in one control subject (227.4 U/ml), with an average value within normal range for these groups (Table 1 and Fig. 1). Disease duration until the test in 3 MSA-C patients with high titers of anti-TPO Ab had tendency to be shorter than in the other groups. Besides that, their clinical manifestations, age and age of the disease onset did not differ from the other patients (Table 2).
3. Statistical analysis
5. Discussion
Descriptive statistics for all measured variables include summary measures (means, standard deviations (SD), medians, percentiles and ranges of descriptive variables were generated as appropriate), and box plots in excel 2007. The Kruskal–Wallis test was used to examine overall differences between the groups. For pairwise comparisons the Mann–Whitney test was used. All statistical analyses were performed using SPSS 21.
Steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT), previously called Hashimoto encephalopathy is a term used to describe a type of encephalopathy of presumed autoimmune origin characterized by high titers of antiTPO Ab [11]. Moreover, in immunofluorescence assays on monkey brain cerebellum sections, both the sera and anti-TPO monoclonal antibodies of a patient with SREAT were able to bind to cerebellar cells expressing glial fibrillary acid protein [11]. Schott and Warren
2.2. Protocol
900 800 700
500
MSA-C
400
cont
300
MSA-P
An-TPO Ab, IU/ml
600
PD
200 100
50 0
PD
MSA-P
MSA-C
cont
MSA-P, the MSA with the predominant motor presentation is parkinsonism; MSA-C, the MSA with the predominant motor presentation is cerebellar; cont, controls; Anti-TPO Ab, Anti-thyroperoxidase antibodies levels, IU/ml; Fig. 1. Antibody levels in the patients and controls. MSA-P: the MSA with the predominant motor presentation is parkinsonism; MSA-C: the MSA with the predominant motor presentation is cerebellar; cont: controls; Anti-TPO Ab: Anti-thyroperoxidase antibodies levels, IU/ml.
2350
B. Shihman et al. / Clinical Neurology and Neurosurgery 115 (2013) 2348–2350
Table 2 Antibody levels in the study patients and controls. MSA-P patients
MSA-C all patients
MSA-C with normal Anti-TPO Ab levels
MSA-C with high Anti-TPO Ab levels
PD patients
Controls*
No. of patients Anti-TPO Ab levels, IU/ml median (IQR)
17 6.4 ± 1.4
11 21.9 ± 6.4
8 13.5 ± 11.6
28 13.0 ± 9. 3
26 11.5 ± 9. 2
Anti-TG Ab levels, IU/ml median (IQR)
7.8 ± 1, 8
47.1 ± 15.3
41.1 ± 42.4
3 Parameters: 352.6 IU/ml 713.6 IU/ml 884.6 IU/ml Parameters: 75.6 IU/ml 139.8 IU/ml 60.7 IU/ml
38.5 ± 29. 7
38.5 ± 23. 9
IQR – interquartile range.
[12] suggested that SREAT should be viewed as a syndrome, but not as a diagnosis. Lee et al. [13] observed higher titers of anti-TG and anti-TPO Ab in their patients with MSA, compared with PD patients. Although ataxia correlated with anti-TG and anti-TPO antibodies, there was no significant difference in the frequency of abnormal titer between MSA-P and MSA-C groups in their study [13]. We identified the presence of elevated anti-TPO levels in our group of MSA-C patients but not in MSA-P or PD patients or in healthy controls. These findings may suggest an autoimmune component in some cases of MSA-C, that is different from the parkinsonian type of MSA, and associated with cerebellar damage. Similar findings were reported in other forms of cerebellar ataxia [14]. Since autopsy data are not available for any of our patients, it is unknown whether the pathology of the MSA-C cases with high anti TPO antibodies is identical to the remainder and contains the same oligodendrocyte changes. Elevated antithyroid antibodies are not rare in apparently normal aging, and a chance occurrence cannot be excluded. Therefore, study of additional MSA patients is required. This report describes a small number of cases. Furthermore, the lack of cerebrospinal fluid examinatioms, and the fact that immunomodulatory drugs have not been administered, limit any attempt to generalize. However, if confirmed, these observations may be significant. In conclusion, anti-TG Ab levels were within the normal range in all MSA patients. The demonstration of highly elevated titers of anti-TPO Ab in some MSA-C patients may support an autoimmune contribution to the pathogenesis of the syndrome. If confirmed, these novel data may have interesting clinical and therapeutic implications [15,16]. Acknowledgment Esther Eshkol is thanked for editorial assistance.
References [1] Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008;71(9):670–6. [2] Trojanowski J. Proposed neuropathological criteria for the postmortem diagnosis of multiple system atrophy. Neuropathol Appl Neurobiol 2007;33:615–20. [3] Vanacore N. Epidemiological evidence on multiple system atrophy. J Neural Transm 2005;112(12):1605–12. [4] Ozawa T. Pathology and genetics of multiple system atrophy: an approach to determining genetic susceptibility spectrum. Acta Neuropathol 2006;112(5):531–8. [5] Manto MU. Hashimoto’s associated ataxia. J Neurol Neurosurg Psychiatry 2002;72(2):277–8. [6] Karni A, Abramsky O. Association of MS with thyroid disorders. Neurology 1999 Sep. [7] Selim M, Drachman DA. Ataxia associated with Hashimoto’s disease: progressive non-familial adult onset cerebellar degeneration with autoimmune thyroiditis. J Neurol Neurosurg Psychiatry 2001;71(1):81–7. [8] Passarella B, Negro C, Nozzoli C, De Marco V, Rini A. Cerebellar subacute syndrome due to corticosteroid-responsive encephalopathy associated with autoimmune thyroiditis (also called “Hashimoto’s encephalopathy”). Clin Ter 2005;156(1–2):13–7. [9] Blanchin S, Coffin C, Viader F, Ruf J, Carayon P, Potier F, et al. Antithyroperoxidase antibodies from patients with Hashimoto’s encephalopathy bind to cerebellar astrocytes. J Neuroimmunol 2007;192(1–2):13–20. [10] Li Y, Teng D, Shan Z, Teng X, Guan H, Yu X, et al. Antithyroperoxidase and.antibodies in a five-year follow-up survey of populations with different iodine intakes. J Clin Endocrinol Metab 2008;93(5):1751–7. [11] Mocellin R, Walerfang M, Velakoulis D. Hashimoto’s encephalopathy: epidemiology, pathogenesis and management. CNS Drugs 2007;21(10):799–811. [12] Schott JM, Warren JD. Steroid responsive encephalopathy with positive thyroid antibodies. A syndrome, not a diagnosis? J Neurol 2007;254(4):542. [13] Lee-WE, Lee TJ, Oh SM, Yoon WT, Cho J, Ahn J, et al. Analysis of serum antithyroid antibodies titers in Parkinson’s Disease and multiple system atrophy. Parkinsonism Relat Disord 2009;15S2:S57. [14] Hadjivassiliou M, Boscolo S, Tongiorgi E, Grünewald RA, Sharrack B, Sanders DS, et al. Cerebellar ataxia as a possible organ-specific autoimmune disease. Mov Disor 2008;23(10):1370–7. [15] Nanri K, Okita M, Takeguchi M, Taguchi T, Ishoko T, Saito H, et al. Intravenous immunoglobulin therapy for autoantibody-positive cerebellar ataxia. Intern Med 2009;48(10):783–90. [16] Novak P, Williams A, Ravin P, Zurkiya O, Abduljalil A, Novak V. Treatment of multiple system atrophy using intravenous immunoglobulin. BMC Neurol 2012;12:131.