Acta Neurol Belg DOI 10.1007/s13760-015-0472-6
LETTER TO THE EDITOR
Balo´-like lesion associated with psoriasis and chronic autoimmune thyroiditis Corina Roman-Filip1 • Aurelian Ungureanu2 • Ileana Pra˘variu3
Received: 9 February 2015 / Accepted: 28 March 2015 Ó Belgian Neurological Society 2015
Keywords Balo´-type lesions Tumefactive lesions Psoriasis Autoimmune thyroiditis T helper 17 cells
The pathological mechanism behind it still remains a debate, although one can find similarities with multiple sclerosis (MS) and even overlapping lesions of these conditions.
Introduction Pathologist Jo´zsef Balo´ described a particular form of demyelinating disease, leukoencephalitis periaxialis concentrica, classically named Balo´’s concentric sclerosis (BCS). Nowadays, this is defined as a variant of multiple sclerosis. The intensive use of magnetic resonance showed an increasing number of different types of demyelinating lesions. Some of these are specific, but a large variety is under debate regarding the classification. Tumefactive demyelinating lesions (pseudotumoral) can sometimes present a degree of concentricity and can be easily mistaken for a genuine Balo´ lesion, or at least a Balo´-like demyelinating lesion. Historically, the variants of multiple sclerosis were regarded as serious disabling inflammatory damages of the central nervous system, but recent works have demonstrated that the course of the disease may be more variable, at least regarding BCS. Imagistic studies can lead to a better appreciation on the prognosis of BCS and its association with other types of demyelinating lesions [1].
& Aurelian Ungureanu [email protected] 1
Neurology Department, Academic Emergency Hospital, ‘‘Lucian Blaga’’ University Sibiu, 2-4 Pompeiu Onofreiu St., 550166 Sibiu, Romania
2
Neurology Department, Aria Clinic, 100 Alba Iulia St., 550052 Sibiu, Romania
3
Radiology Department, Polisano European Hospital, 1A Izvorului St., 550172 Sibiu, Romania
Case report We present the case of a 40-year-old woman admitted for mild incoordination of the left arm and speech impairment. The patient’s medical history is positive for psoriasis (since 2002) and autoimmune thyroiditis under treatment with levothyroxine 50 ug/day (since 2010). Magnetic resonance imaging (MRI) studies revealed FLAIR and T2-weighted inhomogeneous hyperintense lesions with concentric enhanced and non-enhanced lesions on T1 with gadolinium contrast (Fig. 1a, b). The lesion was characterized as atypical demyelinating with 22.5/21.6 mm in size, with late concentric enhancement and without mass effect. Additionally, two demyelinating periventricular enhancing lesions were found (Fig. 1d–f). A biochemistry panel, anti-nuclear antibodies, anti-ds DNA antibodies, ANCA antibodies, anti-Ro antibodies and anti-Borrelia antibodies were negative. Slight pleocytosis (16 cells/mm3 with 75 % monocytes) was detected in the cerebrospinal fluid together with present oligoclonal bands and normal proteins. Serum myelin oligodendrocyte glycoprotein antibodies, myelin basic protein antibodies, IgG anti-aquaporin 4 antibodies were negative. Moreover, a high serum titre of anti-thyroperoxidase antibodies (60.73 IU/mL–normal \5.6 IU/mL) was present with normal TSH, FT3 and FT4 under treatment with levothyroxine. The clinical and imagistic assessments suggested Balo´-like demyelinating lesion associated with psoriasis vulgaris and autoimmune endocrinopathy. After 5 days of intravenous methylprednisolone, one gramme per day, we
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Acta Neurol Belg
Fig. 1 a T1 gadolinium sequence showing a frontal demyelinating lesion with concentric enhancing rings (arrow); b T2-weighted image with concentric rings of demyelination and partially myelinated regions (arrow); c DWI sequence with diffusion restriction in the
active lesion; d T2 hyperintense periventricular lesion (arrowhead); e enhancing periventricular lesion in the occipital lobe (arrowhead); f coronal T2 image showing a small demyelinating lesion (arrowhead) with enhancement on T1 (not shown)
observed significant improvement. A differential diagnosis with MS, acute disseminated encephalomyelitis, lymphoma and central nervous system tumour was made, but all were ruled out by the clinical and imagistic studies. Tumefactive lesion is still a very highly probable radiologic diagnosis. The dimensions must be larger than 2 cm in diameter, with mass effect and open-ring contrast enhancement, with serious disability, which was excluded. Six months later, MRI was significantly improved (Fig. 2) with sustained clinical remission and radiologic improvement. The biochemistry reassessment found high liver enzymes and the patient was evaluated for viral and autoimmune hepatitis (negative antimitochondrial antibodies, anti-LKM1 and anti-smooth muscle fibre antibodies, negative virology). One year later, the patient presents no neurological impairment without any
other immunomodulation or immunosuppressive treatment assigned.
123
Discussion The association of the pathologies described may seem incidental. However, strong research evidence shows the implication of T helper 17 cells (Th17) and Interleukin 17 (Il17) in the autoimmune pathways of MS, autoimmune endocrinopathy and psoriasis [2, 3]. BCS type lesions and MS lesions may both be present simultaneously in the same patient, and Balo´-like lesions may change over time into the classic appearance of MS lesions [4]. The lesions are characteristic, with rings of demyelination, surrounded by
Acta Neurol Belg
Fig. 2 a T1 gadolinium sequence showing a significant improvement 6 months later (arrow); b T2-weighted image showing the demyelinating lesion markedly decreased (arrow); c DWI; d–f improvement of demyelinating lesions
partial demyelinated regions, reflecting the concentricity within the lesion. The lesion type is classified as MS pattern III with oligodendrocyte loss, microglial activation and loss of myelin-associated glycoprotein [4]. Studies of 7 Tesla MRI support the microvascular pathology associated to inflammation, which seems to be consistent with pattern III lesions [5]. These studies are sustained by identifying Notch 3 mutation in a patient with BCS phenotype and a family history of Notch 3 mutation carriers and CADASIL. Mitochondrial respiratory chain disturbance and the expression of some molecules probably tend to precondition hypoxic tissue to inflammation, such as mitochondrial heat shock protein 70 [6]. Furthermore, new cellular biology studies of cancer found that hsp70 can mediate the Th17 differentiation [1]. We consider that the simultaneity with the autoimmune endocrinopathy and psoriasis may be more than incidental and raises the hypothesis of probable linkage of the proinflammatory and autoimmune role of Th17 cells lineage with mitochondrial oxidative stress.
Conflict of interest of interest.
The authors declare that they have no conflict
Ethical approval This chapter does not contain any studies with human participants or animals performed by any of the authors. Informed consent Informed consent was obtained from all individual participants included in the study.
References 1. Hardy TA, Miller DH (2014) Balo´’s concentric sclerosis. Lancet Neurol 13(7):740–746. doi:10.1016/S1474-4422(14)70052-3 2. Kottke T, Sanchez-Perez L, Diaz RM, Thompson J, Chong H, Harrington K, Calderwood SK, Pulido J, Georgopoulos N, Selby P, Melcher A, Vile R (2007) Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer. Cancer Res 67(24):11970–11979 3. Bossowski A, Moniuszko M, Dabrowska M, Rusak M, Jeznach M, Bodzenta-Łukaszyk A, Bossowska A (2013) Role of Th17 cells and IL-17, IL-23 cytokines in pathogenesis of autoimmune thyroid disease in children. Thyroid Res 6(Suppl 2):A8. doi:10.1186/17566614-6-S2-A8
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Acta Neurol Belg 4. Stadelmann C, Ludwin S, Tabira T, Guseo A, Lucchinetti CF, Leel-Ossy L, Ordinario AT, Bru¨ck W, Lassmann H (2005) Tissue preconditioning may explain concentric lesions in Balo´’s type of multiple sclerosis. Brain 128(Pt 5):979–987. doi:10.1093/brain/ awh457 5. Berghoff M, Schlamann MU, Maderwald S, Grams AE, Kaps M, Ladd ME, Gizewski ER (2013) 7 Tesla MRI demonstrates vascular
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pathology in Balo’s concentric sclerosis. Mult Scler 19(1):120–122. doi:10.1177/1352458512445302 6. Chitnis T, Hollmann TJ (2012) CADASIL mutation and Balo concentric sclerosis: a link between demyelination and ischemia? Neurology 78(3):221–223. doi:10.1212/WNL.0b013e31823fcd3c
LETTER TO THE EDITOR
Balo´-like lesion associated with psoriasis and chronic autoimmune thyroiditis Corina Roman-Filip1 • Aurelian Ungureanu2 • Ileana Pra˘variu3
Received: 9 February 2015 / Accepted: 28 March 2015 Ó Belgian Neurological Society 2015
Keywords Balo´-type lesions Tumefactive lesions Psoriasis Autoimmune thyroiditis T helper 17 cells
The pathological mechanism behind it still remains a debate, although one can find similarities with multiple sclerosis (MS) and even overlapping lesions of these conditions.
Introduction Pathologist Jo´zsef Balo´ described a particular form of demyelinating disease, leukoencephalitis periaxialis concentrica, classically named Balo´’s concentric sclerosis (BCS). Nowadays, this is defined as a variant of multiple sclerosis. The intensive use of magnetic resonance showed an increasing number of different types of demyelinating lesions. Some of these are specific, but a large variety is under debate regarding the classification. Tumefactive demyelinating lesions (pseudotumoral) can sometimes present a degree of concentricity and can be easily mistaken for a genuine Balo´ lesion, or at least a Balo´-like demyelinating lesion. Historically, the variants of multiple sclerosis were regarded as serious disabling inflammatory damages of the central nervous system, but recent works have demonstrated that the course of the disease may be more variable, at least regarding BCS. Imagistic studies can lead to a better appreciation on the prognosis of BCS and its association with other types of demyelinating lesions [1].
& Aurelian Ungureanu [email protected] 1
Neurology Department, Academic Emergency Hospital, ‘‘Lucian Blaga’’ University Sibiu, 2-4 Pompeiu Onofreiu St., 550166 Sibiu, Romania
2
Neurology Department, Aria Clinic, 100 Alba Iulia St., 550052 Sibiu, Romania
3
Radiology Department, Polisano European Hospital, 1A Izvorului St., 550172 Sibiu, Romania
Case report We present the case of a 40-year-old woman admitted for mild incoordination of the left arm and speech impairment. The patient’s medical history is positive for psoriasis (since 2002) and autoimmune thyroiditis under treatment with levothyroxine 50 ug/day (since 2010). Magnetic resonance imaging (MRI) studies revealed FLAIR and T2-weighted inhomogeneous hyperintense lesions with concentric enhanced and non-enhanced lesions on T1 with gadolinium contrast (Fig. 1a, b). The lesion was characterized as atypical demyelinating with 22.5/21.6 mm in size, with late concentric enhancement and without mass effect. Additionally, two demyelinating periventricular enhancing lesions were found (Fig. 1d–f). A biochemistry panel, anti-nuclear antibodies, anti-ds DNA antibodies, ANCA antibodies, anti-Ro antibodies and anti-Borrelia antibodies were negative. Slight pleocytosis (16 cells/mm3 with 75 % monocytes) was detected in the cerebrospinal fluid together with present oligoclonal bands and normal proteins. Serum myelin oligodendrocyte glycoprotein antibodies, myelin basic protein antibodies, IgG anti-aquaporin 4 antibodies were negative. Moreover, a high serum titre of anti-thyroperoxidase antibodies (60.73 IU/mL–normal \5.6 IU/mL) was present with normal TSH, FT3 and FT4 under treatment with levothyroxine. The clinical and imagistic assessments suggested Balo´-like demyelinating lesion associated with psoriasis vulgaris and autoimmune endocrinopathy. After 5 days of intravenous methylprednisolone, one gramme per day, we
123
Acta Neurol Belg
Fig. 1 a T1 gadolinium sequence showing a frontal demyelinating lesion with concentric enhancing rings (arrow); b T2-weighted image with concentric rings of demyelination and partially myelinated regions (arrow); c DWI sequence with diffusion restriction in the
active lesion; d T2 hyperintense periventricular lesion (arrowhead); e enhancing periventricular lesion in the occipital lobe (arrowhead); f coronal T2 image showing a small demyelinating lesion (arrowhead) with enhancement on T1 (not shown)
observed significant improvement. A differential diagnosis with MS, acute disseminated encephalomyelitis, lymphoma and central nervous system tumour was made, but all were ruled out by the clinical and imagistic studies. Tumefactive lesion is still a very highly probable radiologic diagnosis. The dimensions must be larger than 2 cm in diameter, with mass effect and open-ring contrast enhancement, with serious disability, which was excluded. Six months later, MRI was significantly improved (Fig. 2) with sustained clinical remission and radiologic improvement. The biochemistry reassessment found high liver enzymes and the patient was evaluated for viral and autoimmune hepatitis (negative antimitochondrial antibodies, anti-LKM1 and anti-smooth muscle fibre antibodies, negative virology). One year later, the patient presents no neurological impairment without any
other immunomodulation or immunosuppressive treatment assigned.
123
Discussion The association of the pathologies described may seem incidental. However, strong research evidence shows the implication of T helper 17 cells (Th17) and Interleukin 17 (Il17) in the autoimmune pathways of MS, autoimmune endocrinopathy and psoriasis [2, 3]. BCS type lesions and MS lesions may both be present simultaneously in the same patient, and Balo´-like lesions may change over time into the classic appearance of MS lesions [4]. The lesions are characteristic, with rings of demyelination, surrounded by
Acta Neurol Belg
Fig. 2 a T1 gadolinium sequence showing a significant improvement 6 months later (arrow); b T2-weighted image showing the demyelinating lesion markedly decreased (arrow); c DWI; d–f improvement of demyelinating lesions
partial demyelinated regions, reflecting the concentricity within the lesion. The lesion type is classified as MS pattern III with oligodendrocyte loss, microglial activation and loss of myelin-associated glycoprotein [4]. Studies of 7 Tesla MRI support the microvascular pathology associated to inflammation, which seems to be consistent with pattern III lesions [5]. These studies are sustained by identifying Notch 3 mutation in a patient with BCS phenotype and a family history of Notch 3 mutation carriers and CADASIL. Mitochondrial respiratory chain disturbance and the expression of some molecules probably tend to precondition hypoxic tissue to inflammation, such as mitochondrial heat shock protein 70 [6]. Furthermore, new cellular biology studies of cancer found that hsp70 can mediate the Th17 differentiation [1]. We consider that the simultaneity with the autoimmune endocrinopathy and psoriasis may be more than incidental and raises the hypothesis of probable linkage of the proinflammatory and autoimmune role of Th17 cells lineage with mitochondrial oxidative stress.
Conflict of interest of interest.
The authors declare that they have no conflict
Ethical approval This chapter does not contain any studies with human participants or animals performed by any of the authors. Informed consent Informed consent was obtained from all individual participants included in the study.
References 1. Hardy TA, Miller DH (2014) Balo´’s concentric sclerosis. Lancet Neurol 13(7):740–746. doi:10.1016/S1474-4422(14)70052-3 2. Kottke T, Sanchez-Perez L, Diaz RM, Thompson J, Chong H, Harrington K, Calderwood SK, Pulido J, Georgopoulos N, Selby P, Melcher A, Vile R (2007) Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer. Cancer Res 67(24):11970–11979 3. Bossowski A, Moniuszko M, Dabrowska M, Rusak M, Jeznach M, Bodzenta-Łukaszyk A, Bossowska A (2013) Role of Th17 cells and IL-17, IL-23 cytokines in pathogenesis of autoimmune thyroid disease in children. Thyroid Res 6(Suppl 2):A8. doi:10.1186/17566614-6-S2-A8
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Acta Neurol Belg 4. Stadelmann C, Ludwin S, Tabira T, Guseo A, Lucchinetti CF, Leel-Ossy L, Ordinario AT, Bru¨ck W, Lassmann H (2005) Tissue preconditioning may explain concentric lesions in Balo´’s type of multiple sclerosis. Brain 128(Pt 5):979–987. doi:10.1093/brain/ awh457 5. Berghoff M, Schlamann MU, Maderwald S, Grams AE, Kaps M, Ladd ME, Gizewski ER (2013) 7 Tesla MRI demonstrates vascular
123
pathology in Balo’s concentric sclerosis. Mult Scler 19(1):120–122. doi:10.1177/1352458512445302 6. Chitnis T, Hollmann TJ (2012) CADASIL mutation and Balo concentric sclerosis: a link between demyelination and ischemia? Neurology 78(3):221–223. doi:10.1212/WNL.0b013e31823fcd3c
