- Email: [email protected]
A case of GFAP-astroglial autoimmunity presenting with reversible parkinsonism
Multiple Sclerosis and Related Disorders 39 (2020) 101900
Contents lists available at ScienceDirect
Multiple Sclerosis and Related Disorders journal homepage: www.elsevier.com/locate/msard
Case report
A case of GFAP-astroglial autoimmunity presenting with reversible parkinsonism
T
Anna Tomczaka, Elaine Sua, Madina Tugizovaa, Aaron M. Carlsonb, Lucas B. Kippa,c, ⁎ Haojun Fenga, May H. Hana,c, a
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, United States Department of Neurology, University of Florida, Gainesville, FL 32610, United States c Multiple Sclerosis Center, Neuroimmunology Division, Stanford University, Stanford, CA 94305, United States b
A R T I C LE I N FO
A B S T R A C T
Keywords: Astroglial autoimmunity Dementia GFAP Immune modulation Parkinsonism
Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a newly recognized autoimmune central nervous system (CNS) inflammatory disorder, presenting with an array of neurological symptoms in association with autoantibodies against GFAP, a hallmark protein expressed on astrocytes. Limited knowledge is available on the disease pathogenesis and clinical outcome. Here, we report a case of autoimmune GFAP astrocytopathy presenting with encephalomyelitis and parkinsonism. Our patient was a 66-year old male who experienced progressive somnolence, apathy, anxiety, right arm tremor, urinary retention, progressive weakness, and falls over the course of three months, followed by acute delusional psychosis. His neurologic exam on hospital admission was notable for cognitive impairment, myoclonus, rigidity, right hand action tremor, bradykinesia, shuffling gait, and dysmetria. Cerebrospinal fluid examination showed elevated protein, lymphocytic pleocytosis, and one unique oligoclonal band. Magnetic resonance imaging (MRI) revealed non-specific T2/FLAIR hyperintensities in the brain and longitudinally extensive transverse myelitis in the cervical spine. FDG-PET showed a pattern of brain uptake suspicious for limbic encephalitis. Serum and CSF paraneoplastic panel showed presence of GFAP immunoglobulin G (IgG). Treatment with corticosteroids resulted in clinical and radiographic improvement. However, the patient was treated with anti-CD20 immunotherapy due to steroid-dependence. This case exemplifies the recently described neurologic syndrome of autoimmune GFAP astrocytopathy presenting with encephalomyelitis and parkinsonism, reversed by B lymphocyte depletion.
1. Introduction
2. Case report
Glial fibrillary acidic protein (GFAP) autoimmunity is a novel astroglial autoimmune disorder characterized by central nervous system (CNS) inflammation in the presence of autoantibodies against GFAP, a component of astrocyte intermediate filament. GFAP IgG has been associated with diverse neurologic presentations, coexisting autoimmune disorders (such as neuromyelitis optica (NMO), diabetes type 1, rheumatoid arthritis), and malignancies (including teratomas and brain tumors) (Flanagan et al., 2017; Fang et al., 2016). The pathogenesis of GFAP autoimmunity is still largely unknown, and few studies have been done in mouse models and patient samples (Long et al., 2018). Here, we report a case of a 66-year-old man with anti-GFAP antibodies, presenting with longitudinally extensive transverse myelitis, psychosis, and reversible parkinsonism.
A 66-year-old man was admitted to the hospital with new onset acute psychosis following two weeks of mood changes and cognitive slowing. The patient reported that three months prior, he had experienced progressive weakness, episodic right arm tremor, multiple falls, difficulty voiding urine, and a 40-pound weight loss. Family history included Parkinson's disease, Alzheimer's dementia, lymphoma, Sjögren's syndrome, and ulcerative colitis. Pertinent positive findings on physical examination at hospital admission included a Montreal Cognitive Assessment (MoCA) score of 22/ 30, hypomimia, saccadic intrusions of smooth pursuit, myoclonus, bradykinesia, right hand action tremor, rigidity, stooped posture, and a shuffling gait. His cranial nerves, strength, and sensory examination were normal.
⁎
Corresponding author at: 1201 Welch Road, Stanford, CA 94305-5489, United States. E-mail addresses: [email protected] (A. Tomczak), [email protected] (E. Su), [email protected] (M. Tugizova), [email protected]fl.edu (A.M. Carlson), [email protected] (L.B. Kipp), [email protected] (M.H. Han). https://doi.org/10.1016/j.msard.2019.101900 Received 7 November 2019; Received in revised form 11 December 2019; Accepted 18 December 2019 2211-0348/ © 2019 Elsevier B.V. All rights reserved.
Multiple Sclerosis and Related Disorders 39 (2020) 101900
A. Tomczak, et al.
Fig. 1. PATIENT'S BRAIN MRI AND IMMUNOHISTOCHEMISTRY STAINING. Initial (A) susceptibility-weighted images of the brain. Arrows indicate bilateral attenuation of nigrosome-1. Comparison of the staining pattern between commercial anti-GFAP and patient's purified serum as shown by immunohistochemistry of control (healthy) brain tissue. Immunohistochemistry with (B) commercial anti-GFAP, (C) patient's purified serum (collected prior to treatment with anti-CD20). Arrows indicate astrocytes (black) and neurons (red). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
recognized in 2016, in patients with meningoencephalomyelitis, most commonly presenting with cognitive impairment (memory loss, confusion), psychiatric symptoms, headaches, vision changes, myelitis, nausea, and ataxia (Flanagan et al., 2017; Fang et al., 2016; Long et al., 2018; Li et al., 2018; Yang et al., 2017). Patients also presented with coexisting autoimmune disorders (diabetes type 1, rheumatoid arthritis, Sjögren's syndrome, NMO), autoantibodies (Flanagan et al., 2017; Fang et al., 2016; Long et al., 2018; Li et al., 2018; Yang et al., 2017), paraneoplastic syndromes (Flanagan et al., 2017; Fang et al., 2016), and infectious diseases (Li et al., 2018; Yang et al., 2017). Our patient was not found to have any other autoimmune disorders, autoantibodies, malignancies, or infections. Unlike in other cases, our patient's white matter was largely within normal limits on brain MRI. Interestingly, our patient presented with subacute onset of parkinsonism, and was noted to have attenuated signal in bilateral nigrosome-1, the posterior aspects of the substantia nigra which are typically affected in Parkinson's disease. GFAP autoimmunity is largely understood to be an astrocytopathy, with demonstrated astrocyte-restricted staining patterns (Flanagan et al., 2017). However, immunohistochemistry with our patient's serum resulted in primarily neuronal staining, with some staining of astrocytes (Fig. 1). We were unable to compare these results with staining using the patient's CSF, though there have been reports of correlations between GFAP levels in CSF and serum, in which CSF GFAP are more strongly correlated with disease duration (Abdelhak et al., 2019; Watanabe et al., 2019). GFAP neuronal expression has been reported in the human hippocampus, and its expression has been associated with Alzheimer pathology (Hol et al., 2003). Although there may be other uncharacterized anti-neuronal antibodies in the patient's serum, it is possible that anti-GFAP mediates cross-reactivity to neurons, explaining phenomena such as cognitive and behavioral impairments, as well as attenuation of nigrosome-1 on SWI. GFAP astrocytopathy may also have contributed to our patient's parkinsonism. The degeneration of dopaminergic neurons in the substantia nigra pars compacta is thought to be a neuroinflammatory process in which reactive astrocytes play a key role, and multiple genes implicated in Parkinson disease are important for astrocyte activation (Booth et al., 2017). Disruption of normal inflammatory signaling pathways, which may be initiated by anti-GFAP antibodies, may alter astrocyte functions critical for maintaining neuronal health, leading to the degeneration of dopaminergic neurons. Here we present a patient with GFAP autoimmune disease, presenting with reversible encephalomyelitis and parkinsonism. Though GFAP autoimmunity had previously been understood as an astrocytopathy, our case suggests that neuronal effects may also play a role in the
The differential diagnosis included autoimmune etiology, both primary (e.g., GAD65 spectrum disorders, neuromyelitis optica spectrum disorder (NMOSD), sarcoidosis) and paraneoplastic autoimmunity. Extensive evaluation for inflammatory, infectious, and autoimmune conditions was unrevealing. These included tests for ANA, Anti-TPO, autoimmune encephalitis, anti-Ma, anti-GAD, NMO, MOG, DPPX, GlyR and ANCA. Autonomic testing was unremarkable. Neuropsychological testing showed evidence of cognitive slowing involving executive functioning, phonemic word generation, design generation, as well as difficulty on the Wisconsin Card Sorting Test. Cerebrospinal fluid showed lymphocytic pleocytosis (89% lymphocytes, WBC of 54), elevated protein of 97 mg/dL (normal range 15–60 mg/dL), and a unique oligoclonal band. Magnetic resonant imaging (MRI) of the brain and spine showed nonspecific white matter changes, attenuated nigrosomes on susceptibility-weighted images (SWI), and a non-enhancing T2 signal abnormality spanning from C2-T1, respectively. FDG-PET scan was negative for malignancy, however, there was enhanced uptake in the mesial temporal lobes and the posterior aspect of the cingulate gyrus of the brain was noted. Paraneoplastic panel returned positive for anti-GFAP antibody in both serum and CSF by immunofluorescent assay. Neither ropinirole nor carbidopa/levodopa improved the patient's parkinsonian symptoms. However, three days of high dose intravenous methylprednisolone, followed by oral prednisone taper, fully resolved patient's bradykinesia, tremor, rigidity, posture, and gait. Follow-up MRI a month later showed residual T2 signal abnormality in C3-C7 in the spinal MRI. Brain MRI showed normal normalization white matter T2 signal abnormalities. SWI sequences were not included, so we were unable to reassess the nigrosomes visualized in the initial scan. The patient was then treated with anti-CD20 monoclonal antibody, rituximab, due to recurrent symptoms when tapering prednisone below 40 mg daily. Mycophenolate mofetil was later added to the regimen as he was unable to wean off prednisone despite further improvement of function, an improved MoCA score of 28/30, a CD19 count of zero, and undetectable serum anti-GFAP titers. 3. Discussion Movement disorders in patients with GFAP autoimmunity have previously been reported (Long et al., 2018; Kimura et al., 2019), but to the best of our knowledge, our case describes the first case of GFAPastroglial autoimmunity associated with parkinsonism. Our patient's parkinsonism, though responsive to steroids, required maintenance immune suppression for sustained remission, suggesting chronicity of his anti-GFAP autoimmunity. CNS autoimmunity with antibodies against GFAP was first 2
Multiple Sclerosis and Related Disorders 39 (2020) 101900
A. Tomczak, et al.
diverse clinical presentations of this novel entity.
References
4. Financial disclosures
Flanagan, E.P., Hinson, S.R., Lennon, V.A., et al., 2017. Glial fibrillary acidic protein immunoglobulin g as biomarker of autoimmune astrocytopathy: analysis of 102 patients. Ann. Neurol. 81 (2), 298–309. https://doi.org/10.1002/ana.24881. Fang, B., McKeon, A., Hinson, S.R., et al., 2016. Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol. 73 (11), 1297–1307. https://doi.org/10.1001/jamaneurol.2016.2549. Long, Y., Liang, J., Xu, H., et al., 2018. Autoimmune glial fibrillary acidic protein astrocytopathy in Chinese patients: a retrospective study. Eur. J. Neurol. 25 (3), 477–483. https://doi.org/10.1111/ene.13531. Kimura, A., Takekoshi, A., Yoshikura, N., Hayashi, Y., Shimohata, T, 2019. Clinical characteristics of autoimmune GFAP astrocytopathy. J. Neuroimmunol. 332 (March), 91–98. https://doi.org/10.1016/j.jneuroim.2019.04.004. Li, J., Xu, Y., Ren, H., Zhu, Y., Peng, B., Cui, L., 2018. Autoimmune GFAP astrocytopathy after viral encephalitis: a case report. Mult. Scler. Relat. Disord. 21, 84–87. https:// doi.org/10.1016/j.msard.2018.02.020. Yang, X., Liang, J., Huang, Q., et al., 2017. Treatment of autoimmune glial fibrillary acidic protein astrocytopathy: follow-up in 7 cases. Neuroimmunomodulation 24 (2), 113–119. https://doi.org/10.1159/000479948. Abdelhak, A., Hottenrott, T., Morenas-Rodríguez, E., et al., 2019. Glial activation markers in CSF and serum from patients with primary progressive multiple sclerosis: potential of serum GFAP as disease severity marker. Front. Neurol. 10 (March), 1–9. https:// doi.org/10.3389/fneur.2019.00280. Watanabe, M., Nakamura, Y., Michalak, Z., et al., 2019. Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD. Neurology 93 (13), e1299–e1311. https://doi.org/10.1212/WNL.0000000000008160. Hol, E.M., Roelofs, R.F., Moraal, E., et al., 2003. Neuronal expression of GFAP in patients with Alzheimer pathology and identification of novel GFAP splice forms. Mol. Psychiatry 8 (9), 786–796. https://doi.org/10.1038/sj.mp.4001379. Booth, H.D.E., Hirst, W.D., Wade-Martins, R, 2017. The role of astrocyte dysfunction in Parkinson's disease pathogenesis. Trends Neurosci. 40 (6), 358–370. https://doi.org/ 10.1016/j.tins.2017.04.001.
None Study funded by This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. CRediT authorship contribution statement Anna Tomczak: Investigation, Writing - original draft. Elaine Su: Writing - review & editing. Madina Tugizova: Writing - review & editing. Aaron M. Carlson: Writing - review & editing. Lucas B. Kipp: Writing - review & editing. Haojun Feng: Writing - review & editing. May H. Han: Supervision, Writing - review & editing. Declaration of Competing Interest None. Acknowledgments None.
3
Contents lists available at ScienceDirect
Multiple Sclerosis and Related Disorders journal homepage: www.elsevier.com/locate/msard
Case report
A case of GFAP-astroglial autoimmunity presenting with reversible parkinsonism
T
Anna Tomczaka, Elaine Sua, Madina Tugizovaa, Aaron M. Carlsonb, Lucas B. Kippa,c, ⁎ Haojun Fenga, May H. Hana,c, a
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, United States Department of Neurology, University of Florida, Gainesville, FL 32610, United States c Multiple Sclerosis Center, Neuroimmunology Division, Stanford University, Stanford, CA 94305, United States b
A R T I C LE I N FO
A B S T R A C T
Keywords: Astroglial autoimmunity Dementia GFAP Immune modulation Parkinsonism
Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a newly recognized autoimmune central nervous system (CNS) inflammatory disorder, presenting with an array of neurological symptoms in association with autoantibodies against GFAP, a hallmark protein expressed on astrocytes. Limited knowledge is available on the disease pathogenesis and clinical outcome. Here, we report a case of autoimmune GFAP astrocytopathy presenting with encephalomyelitis and parkinsonism. Our patient was a 66-year old male who experienced progressive somnolence, apathy, anxiety, right arm tremor, urinary retention, progressive weakness, and falls over the course of three months, followed by acute delusional psychosis. His neurologic exam on hospital admission was notable for cognitive impairment, myoclonus, rigidity, right hand action tremor, bradykinesia, shuffling gait, and dysmetria. Cerebrospinal fluid examination showed elevated protein, lymphocytic pleocytosis, and one unique oligoclonal band. Magnetic resonance imaging (MRI) revealed non-specific T2/FLAIR hyperintensities in the brain and longitudinally extensive transverse myelitis in the cervical spine. FDG-PET showed a pattern of brain uptake suspicious for limbic encephalitis. Serum and CSF paraneoplastic panel showed presence of GFAP immunoglobulin G (IgG). Treatment with corticosteroids resulted in clinical and radiographic improvement. However, the patient was treated with anti-CD20 immunotherapy due to steroid-dependence. This case exemplifies the recently described neurologic syndrome of autoimmune GFAP astrocytopathy presenting with encephalomyelitis and parkinsonism, reversed by B lymphocyte depletion.
1. Introduction
2. Case report
Glial fibrillary acidic protein (GFAP) autoimmunity is a novel astroglial autoimmune disorder characterized by central nervous system (CNS) inflammation in the presence of autoantibodies against GFAP, a component of astrocyte intermediate filament. GFAP IgG has been associated with diverse neurologic presentations, coexisting autoimmune disorders (such as neuromyelitis optica (NMO), diabetes type 1, rheumatoid arthritis), and malignancies (including teratomas and brain tumors) (Flanagan et al., 2017; Fang et al., 2016). The pathogenesis of GFAP autoimmunity is still largely unknown, and few studies have been done in mouse models and patient samples (Long et al., 2018). Here, we report a case of a 66-year-old man with anti-GFAP antibodies, presenting with longitudinally extensive transverse myelitis, psychosis, and reversible parkinsonism.
A 66-year-old man was admitted to the hospital with new onset acute psychosis following two weeks of mood changes and cognitive slowing. The patient reported that three months prior, he had experienced progressive weakness, episodic right arm tremor, multiple falls, difficulty voiding urine, and a 40-pound weight loss. Family history included Parkinson's disease, Alzheimer's dementia, lymphoma, Sjögren's syndrome, and ulcerative colitis. Pertinent positive findings on physical examination at hospital admission included a Montreal Cognitive Assessment (MoCA) score of 22/ 30, hypomimia, saccadic intrusions of smooth pursuit, myoclonus, bradykinesia, right hand action tremor, rigidity, stooped posture, and a shuffling gait. His cranial nerves, strength, and sensory examination were normal.
⁎
Corresponding author at: 1201 Welch Road, Stanford, CA 94305-5489, United States. E-mail addresses: [email protected] (A. Tomczak), [email protected] (E. Su), [email protected] (M. Tugizova), [email protected]fl.edu (A.M. Carlson), [email protected] (L.B. Kipp), [email protected] (M.H. Han). https://doi.org/10.1016/j.msard.2019.101900 Received 7 November 2019; Received in revised form 11 December 2019; Accepted 18 December 2019 2211-0348/ © 2019 Elsevier B.V. All rights reserved.
Multiple Sclerosis and Related Disorders 39 (2020) 101900
A. Tomczak, et al.
Fig. 1. PATIENT'S BRAIN MRI AND IMMUNOHISTOCHEMISTRY STAINING. Initial (A) susceptibility-weighted images of the brain. Arrows indicate bilateral attenuation of nigrosome-1. Comparison of the staining pattern between commercial anti-GFAP and patient's purified serum as shown by immunohistochemistry of control (healthy) brain tissue. Immunohistochemistry with (B) commercial anti-GFAP, (C) patient's purified serum (collected prior to treatment with anti-CD20). Arrows indicate astrocytes (black) and neurons (red). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
recognized in 2016, in patients with meningoencephalomyelitis, most commonly presenting with cognitive impairment (memory loss, confusion), psychiatric symptoms, headaches, vision changes, myelitis, nausea, and ataxia (Flanagan et al., 2017; Fang et al., 2016; Long et al., 2018; Li et al., 2018; Yang et al., 2017). Patients also presented with coexisting autoimmune disorders (diabetes type 1, rheumatoid arthritis, Sjögren's syndrome, NMO), autoantibodies (Flanagan et al., 2017; Fang et al., 2016; Long et al., 2018; Li et al., 2018; Yang et al., 2017), paraneoplastic syndromes (Flanagan et al., 2017; Fang et al., 2016), and infectious diseases (Li et al., 2018; Yang et al., 2017). Our patient was not found to have any other autoimmune disorders, autoantibodies, malignancies, or infections. Unlike in other cases, our patient's white matter was largely within normal limits on brain MRI. Interestingly, our patient presented with subacute onset of parkinsonism, and was noted to have attenuated signal in bilateral nigrosome-1, the posterior aspects of the substantia nigra which are typically affected in Parkinson's disease. GFAP autoimmunity is largely understood to be an astrocytopathy, with demonstrated astrocyte-restricted staining patterns (Flanagan et al., 2017). However, immunohistochemistry with our patient's serum resulted in primarily neuronal staining, with some staining of astrocytes (Fig. 1). We were unable to compare these results with staining using the patient's CSF, though there have been reports of correlations between GFAP levels in CSF and serum, in which CSF GFAP are more strongly correlated with disease duration (Abdelhak et al., 2019; Watanabe et al., 2019). GFAP neuronal expression has been reported in the human hippocampus, and its expression has been associated with Alzheimer pathology (Hol et al., 2003). Although there may be other uncharacterized anti-neuronal antibodies in the patient's serum, it is possible that anti-GFAP mediates cross-reactivity to neurons, explaining phenomena such as cognitive and behavioral impairments, as well as attenuation of nigrosome-1 on SWI. GFAP astrocytopathy may also have contributed to our patient's parkinsonism. The degeneration of dopaminergic neurons in the substantia nigra pars compacta is thought to be a neuroinflammatory process in which reactive astrocytes play a key role, and multiple genes implicated in Parkinson disease are important for astrocyte activation (Booth et al., 2017). Disruption of normal inflammatory signaling pathways, which may be initiated by anti-GFAP antibodies, may alter astrocyte functions critical for maintaining neuronal health, leading to the degeneration of dopaminergic neurons. Here we present a patient with GFAP autoimmune disease, presenting with reversible encephalomyelitis and parkinsonism. Though GFAP autoimmunity had previously been understood as an astrocytopathy, our case suggests that neuronal effects may also play a role in the
The differential diagnosis included autoimmune etiology, both primary (e.g., GAD65 spectrum disorders, neuromyelitis optica spectrum disorder (NMOSD), sarcoidosis) and paraneoplastic autoimmunity. Extensive evaluation for inflammatory, infectious, and autoimmune conditions was unrevealing. These included tests for ANA, Anti-TPO, autoimmune encephalitis, anti-Ma, anti-GAD, NMO, MOG, DPPX, GlyR and ANCA. Autonomic testing was unremarkable. Neuropsychological testing showed evidence of cognitive slowing involving executive functioning, phonemic word generation, design generation, as well as difficulty on the Wisconsin Card Sorting Test. Cerebrospinal fluid showed lymphocytic pleocytosis (89% lymphocytes, WBC of 54), elevated protein of 97 mg/dL (normal range 15–60 mg/dL), and a unique oligoclonal band. Magnetic resonant imaging (MRI) of the brain and spine showed nonspecific white matter changes, attenuated nigrosomes on susceptibility-weighted images (SWI), and a non-enhancing T2 signal abnormality spanning from C2-T1, respectively. FDG-PET scan was negative for malignancy, however, there was enhanced uptake in the mesial temporal lobes and the posterior aspect of the cingulate gyrus of the brain was noted. Paraneoplastic panel returned positive for anti-GFAP antibody in both serum and CSF by immunofluorescent assay. Neither ropinirole nor carbidopa/levodopa improved the patient's parkinsonian symptoms. However, three days of high dose intravenous methylprednisolone, followed by oral prednisone taper, fully resolved patient's bradykinesia, tremor, rigidity, posture, and gait. Follow-up MRI a month later showed residual T2 signal abnormality in C3-C7 in the spinal MRI. Brain MRI showed normal normalization white matter T2 signal abnormalities. SWI sequences were not included, so we were unable to reassess the nigrosomes visualized in the initial scan. The patient was then treated with anti-CD20 monoclonal antibody, rituximab, due to recurrent symptoms when tapering prednisone below 40 mg daily. Mycophenolate mofetil was later added to the regimen as he was unable to wean off prednisone despite further improvement of function, an improved MoCA score of 28/30, a CD19 count of zero, and undetectable serum anti-GFAP titers. 3. Discussion Movement disorders in patients with GFAP autoimmunity have previously been reported (Long et al., 2018; Kimura et al., 2019), but to the best of our knowledge, our case describes the first case of GFAPastroglial autoimmunity associated with parkinsonism. Our patient's parkinsonism, though responsive to steroids, required maintenance immune suppression for sustained remission, suggesting chronicity of his anti-GFAP autoimmunity. CNS autoimmunity with antibodies against GFAP was first 2
Multiple Sclerosis and Related Disorders 39 (2020) 101900
A. Tomczak, et al.
diverse clinical presentations of this novel entity.
References
4. Financial disclosures
Flanagan, E.P., Hinson, S.R., Lennon, V.A., et al., 2017. Glial fibrillary acidic protein immunoglobulin g as biomarker of autoimmune astrocytopathy: analysis of 102 patients. Ann. Neurol. 81 (2), 298–309. https://doi.org/10.1002/ana.24881. Fang, B., McKeon, A., Hinson, S.R., et al., 2016. Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol. 73 (11), 1297–1307. https://doi.org/10.1001/jamaneurol.2016.2549. Long, Y., Liang, J., Xu, H., et al., 2018. Autoimmune glial fibrillary acidic protein astrocytopathy in Chinese patients: a retrospective study. Eur. J. Neurol. 25 (3), 477–483. https://doi.org/10.1111/ene.13531. Kimura, A., Takekoshi, A., Yoshikura, N., Hayashi, Y., Shimohata, T, 2019. Clinical characteristics of autoimmune GFAP astrocytopathy. J. Neuroimmunol. 332 (March), 91–98. https://doi.org/10.1016/j.jneuroim.2019.04.004. Li, J., Xu, Y., Ren, H., Zhu, Y., Peng, B., Cui, L., 2018. Autoimmune GFAP astrocytopathy after viral encephalitis: a case report. Mult. Scler. Relat. Disord. 21, 84–87. https:// doi.org/10.1016/j.msard.2018.02.020. Yang, X., Liang, J., Huang, Q., et al., 2017. Treatment of autoimmune glial fibrillary acidic protein astrocytopathy: follow-up in 7 cases. Neuroimmunomodulation 24 (2), 113–119. https://doi.org/10.1159/000479948. Abdelhak, A., Hottenrott, T., Morenas-Rodríguez, E., et al., 2019. Glial activation markers in CSF and serum from patients with primary progressive multiple sclerosis: potential of serum GFAP as disease severity marker. Front. Neurol. 10 (March), 1–9. https:// doi.org/10.3389/fneur.2019.00280. Watanabe, M., Nakamura, Y., Michalak, Z., et al., 2019. Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD. Neurology 93 (13), e1299–e1311. https://doi.org/10.1212/WNL.0000000000008160. Hol, E.M., Roelofs, R.F., Moraal, E., et al., 2003. Neuronal expression of GFAP in patients with Alzheimer pathology and identification of novel GFAP splice forms. Mol. Psychiatry 8 (9), 786–796. https://doi.org/10.1038/sj.mp.4001379. Booth, H.D.E., Hirst, W.D., Wade-Martins, R, 2017. The role of astrocyte dysfunction in Parkinson's disease pathogenesis. Trends Neurosci. 40 (6), 358–370. https://doi.org/ 10.1016/j.tins.2017.04.001.
None Study funded by This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. CRediT authorship contribution statement Anna Tomczak: Investigation, Writing - original draft. Elaine Su: Writing - review & editing. Madina Tugizova: Writing - review & editing. Aaron M. Carlson: Writing - review & editing. Lucas B. Kipp: Writing - review & editing. Haojun Feng: Writing - review & editing. May H. Han: Supervision, Writing - review & editing. Declaration of Competing Interest None. Acknowledgments None.
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