Clinical Characteristics Of Patients With Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy

BackgroundThe Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy（GFAP-A）is the autoimmune disease which responds well to steroid.Its main clinical phenotype is meningoencephalomyelitis.The specific biomarker is GFAP antibody.The main clinical manifestations are fever,headache,encephalopathy,movement disorders,autonomic nervous dysfunction,myelopathy,abnormal vision and so on.Cerebrospinal fluid showed inflammatory changes,including increased white blood cell count and protein content,some of which were accompanied by low sugar and low chlorine in cerebrospinal fluid,and some were difficult to distinguish from infectious diseases of the central nervous system,which was often misdiagnosed as tuberculous meningitis.The patient’s brain lesions are variable,and the MRI enhancement sequence typically shows radial vascular enhancement perpendicular to the lateral ventricle.Patients with GFAP-A respond well to first-line immunotherapy such as corticosteroids,but some patients require long-term immunosuppressive therapy.There are no guidelines or expert consensus of the diagnosis and treatment of GFAP-A.ObjectivesThe demographic characteristics,clinical manifestations,cerebrospinal fluid,electrophysiology and magnetic resonance imaging characteristics of patients with GFAP-A from two clinical centers（the Second Affiliated Hospital of Guangzhou Medical University and Guangdong 999 Hospital）were analyzed,so as to provide reference for diagnosis and treatment of GFAP-A.MethodsPatients with GFAP-A admitted to the Second Affiliated Hospital of Guangzhou Medical University and Guangdong 999 Brain Hospital from April 2015 to March2023 were retrospectively included.Demographic characteristics,clinical manifestati--ons,cerebrospinal fluid,magnetic resonance imaging,electrophysiological examina--tion,acute treatment and outcome of the patients were collected,and the data was summarized.Results（1）Demographic characteristics:A total of 118 patients with GFAP-A were enrolled in this study,including 71 from the Second Affiliated Hospital of Guangzhou Medical University and 47 from Guangdong 999 Brain Hospital.Among the 118patients included,74（62.7%）patients were males and 44（37.3%）patients were females,with a male-to-female ratio of 1.7:1.The median age of onset was 49.0（36.0-62.0）years old.（2）Clinical manifestations:118 of GFAP-A were mainly acute or subacute.25patients（25/118,21.2%）had a history of preinfection,including 22 patients（22/25,88.0%）with respiratory tract infection,2 patients（2/25,8%）with urinary tract infection,and 1 patient（1/25,4.0%）with digestive system infection.The main clinical manifestations of GFAP-A are:fever（60/118,50.8%）,fatigue（58/118,49.2%）,headache（54/118,45.8%）,dizziness（33/118,28.0%）,abnormal mental behavior（27/118,22.9%）,urinary disorders（25/118,21.2%）,disturbance of consciousness（21/118,17.8%）,and numbness of limbs（21/118,17.8%）,defecation disorder（17/118,14.4%）,abnormal vision（16/118,13.6%）,epilepsy（15/118,12.7%）,nausea and vomiting（15/118,12.7%）,dysarthria（10/118,8.5%）,cognitive impairments（9/118,7.6%）,drinking cough（8/118,6.8%）,ataxia（8/118,6.8%）,double vision（7/118,5.9%）,involuntary movement（5/118,4.2%）,hiccups（4/118,3.4%）,visual field defect（2/118,1.7%）.MRS of 53.4%（63/118）of patients was more than 3 at admission and MRS of 32.2%（38/118）of patients was more than 3 at discharge.（3）Cerebrospinal fluid:There were 27 patients（27/118,22.9%）whose pressure of lumbar puncture was more than 200 mm H₂O.Cerebrospinal fluid test showed leukocytosis with a median of 30.0×10⁶/L and increased protein with a median of759.5 mg/L.The glucose of 25 patients（25/118,21.2%）was less than 2.5 mmol/L in Cerebrospinal fluid.（4）Imaging:54 patients（54/107,50.5%）had abnormal T2/FLAIR sequence in brain MRI.The lesion site is variable,It mainly included brain stem（21/107,19.6%）,brain lobe（20/107,18.7%）,basal ganglia region（19/107,17.8%）,white matter（15/107,14.1%）,thalamus（10/107,9.3%）,cerebellum（8/107,7.5%）,corpus callosum（7/107,6.5%）,corona radiata（5/107,4.7%）and hemioval center（5/107,4.7%）,hippocampus（4/107,3.7%）,internal capsule（1/107,0.9%）and skull（1/107,0.9%）.61 patients（61/91,67.0%）had abnormal enhancement of brain MRI enhanced sequences.Linear enhancement of vertical lateral ventricle was found in 29 patients（29/91,31.9%）.The spinal lesion mainly involved the thoracic spinal cord and meningeal,and a total of 26 patients（26/69,37.7%）had longitudinal extensive long segment lesions（≥3 segments）.（5）Electrophysiology:Electroencephalogram examination showed that 51patients（51/71,71.8%）had abnormalities electroencephalogram,mainly slow wave,some patients could have epilepsy wave.Electromyography suggested that GFAP-A could involve peripheral nerves.18 patients（18/42,42.9%）of patients had abnormal electromyography.Among them,13 patients（13/18,72.2%）involved peripheral motor nerves,6 patients（6/18,33.3%）involved peripheral sensory nerves,4 patients（4/18,22.2%）involved peripheral motor and sensory nerves,11 patients（11/18,61.1%）involved multiple peripheral neuropathy,12 patients（12/18,66.7%）involved peripheral nerve roots.Abnormal sympathetic skin reaction in 10 patients（10/34,29.4%）.（6）Treatment and outcome:In the acute phase,104 patients（104/118,88.1%）were treated with corticosteroid.64 patients（64/118,54.2%）were treated with gamma globulin.Immunosorption was performed in 7 patients（7/118,5.9%）and plasma exchange in 5 patients（5/118,4.2%）,17 patients（17/118,14.4%）took immunosuppressant orally.The treatment of only corticosteroid pulse showed the most obvious improvement.After treatment,there were 79 patients（79/118,67.0%）with m RS improved,34 patients（34/118,28.8%）with m RS no changed,and 5patients（5/118,4.2%）with m RS aggravated,of which 2 patients（2/118,1.7%）died in hospital.Conclusion（1）The onset age of patients with GFAP-A is mainly in middle age,and most of them are male.（2）There may be pre-infection symptoms before the onset of GFAP-A.The main clinical manifestations are fever,weakness,headache,dizziness,abnormal mental behavior,urination and defecation disorders,consciousness disorders,numbness,abnormal vision and so on.（3）The Cerebrospinal fluid of patients with GFAP-A showed inflammatory changes,which needed to be distinguished from infectious diseases of the central nervous system.（4）The lesions of patients with GFAP-A are variable,mainly involving brainstem, cerebral lobe,basal ganglia region,white matter,thalamus,and meninges.The spinal cord was mainly involved in the thoracic spinal cord.（5）The patients of GFAP-A have good response to corticosteroid,and a few had a poor response.