Anti-glial Fibrillary Acidic Protein Research Articles

Assessment of glial fibrillary acidic protein and anti-glial fibrillary acidic protein autoantibody concentrations and necrotising meningoencephalitis risk genotype in dogs with pug dog myelopathy.

Pugs commonly present with thoracolumbar myelopathy, also known as pug dog myelopathy (PDM), which is clinically characterised by progressive signs involving the pelvic limbs, no apparent signs of pain and, often, incontinence. In addition to meningeal fibrosis and focal spinal cord destruction, histopathology has confirmed lymphohistiocytic infiltrates in the central nervous system (CNS) in a considerable number of pugs with PDM. Lymphohistiocytic CNS inflammation also characterises necrotising meningoencephalitis (NME) in pugs. This study aimed to investigate the potential contribution of an immunological aetiology to the development of PDM. The concentrations of glial fibrillary acidic protein (GFAP) in serum and CSF and of anti-GFAP autoantibodies in CSF were measured with an ELISA. In addition, a commercial test was used for genetic characterisation of the dog leukocyte antigen class II haplotype, which is associated with NME susceptibility. This study included 87 dogs: 52 PDM pugs, 14 control pugs, four NME pugs and 17 dogs of breeds other than pugs that were investigated for neurological disease (neuro controls). Anti-GFAP autoantibodies were present in 15 of 19 (79%) of the PDM pugs tested versus six of 16 (38%) of the neuro controls tested (p = 0.018). All 18 PDM pugs evaluated had detectable CSF GFAP. Serum GFAP was detected in two of three (67%) of the NME pugs and in two of 11 (18%) of the control pugs but not in any of the 40 tested PDM pugs. Male pugs heterozygous for the NME risk haplotype had an earlier onset of clinical signs (70 months) compared to male pugs without the risk haplotype (78 months) (p = 0.036). The study was limited bythe lack of healthy dogs of breeds other than pugs and the small numbers of control pugs and pugs with NME. The high proportion of PDM pugs with anti-GFAP autoantibodies and high CSF GFAP concentrations provide support for a potential immunological contribution to the development of PDM.

A Case of Anti-Glial Fibrillary Acidic Protein (GFAP) Antibody-associated Arachnoiditis Presenting as Cauda Equina Syndrome (P5-14.008)

A Case of Anti-Glial Fibrillary Acidic Protein (GFAP) Antibody-associated Arachnoiditis Presenting as Cauda Equina Syndrome (P5-14.008)

New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis.

Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8+/perforin+/granzyme A/B+ cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions.Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies.

Peripheral neuropathy associated with severe glial fibrillary acidic protein (GFAP) astrocytopathy: a case report

A 44-year-old man was admitted due to a fever. He developed unconsciousness and respiratory failure, necessitating mechanical ventilation. After the administration of methylprednisolone and intravenous immunoglobulin for suspected autoimmune encephalitis, his consciousness and respiratory state improved. However, he exhibited pronounced tetraparalysis and impaired sensation below the neck. A spinal MRI revealed swelling of the entire spinal cord, indicating myelitis. Deep tendon reflexes were diminished in all extremities, and a nerve conduction study confirmed motor-dominant axonal polyneuropathy. Subsequently, he developed a fever and headache. Brain MRI demonstrated FLAIR hyperintensities in the basal ganglia and brain stem. CSF analysis for anti-glial fibrillary acidic protein (GFAP) antibody turned out positive, leading to the diagnosis of GFAP astrocytopathy. Although the steroid re-administration improved muscle strength in his upper limbs and reduced the range of diminished sensation, severe hemiparalysis remained. Severe GFAP astrocytopathy can be involved with polyneuropathy. Early detection and therapeutic intervention for this condition may lead to a better prognosis.

CdTe quantum dots as fluorescent nanotools for in vivo glioblastoma imaging

Glioblastoma (GBM) is the most aggressive and infiltrating primary tumor of the central nervous system (CNS), showing a variety of mutations and a high degree of vascularity, cell polymorphism, and nuclear atypia. GBM treatment often recurs to surgical resection, but such protocol lacks efficacy since complete tumor removal is not entirely successful due to invasive cells that cannot be detected at the moment of the surgery. Here, we describe a new in vivo targeting and imaging method for GBM detection in an orthotropic mouse model using fluorescent CdTe quantum dots (CdTe QDs) conjugated to anti-glial fibrillary acidic protein (anti-GFAP). We conjugated and optimized red-emitting CdTe QDs to anti-GFAP to label GBM (U87 cell line) in vivo. The in vivo tumor growth was visualized by the hematoxylin and eosin staining and showed the successful delivery of GBM cells into the mouse brain parenchyma. CdTe/anti-GFAP QDs were injected into the tumor region, and their uptake by tumor cells was visualized by fluorescence microscopy, showing a specific dual labeling with vimentin-immunoreactive GBM. The results reported here provide new perspectives for using CdTe QDs in GBM detection, suggesting their potential application in imaging-guided surgery and a potential fluorescent tool to be applied in the monitoring of 3D tumor glial cultures.

Magnetic Resonance Imaging Combined with Histological Techniques for Dynamic Assessment of Cytotoxic Edema after Cerebral Ischemia-Reperfusion Injury.

Reperfusion therapy after ischemic cerebral stroke may cause cerebral ischemia-reperfusion injury (CIRI), and cerebral edema is an important factor that may aggravate CIRI. Our study aimed to dynamically monitor the development of early cytotoxic edema after CIRI by magnetic resonance imaging (MRI) and to validate it using multiple histological imaging methods. Male Sprague Dawley rats were divided into sham and CIRI groups. T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)-MRI scans were performed in the sham and CIRI groups after reperfusion. Relative apparent diffusion coefficient (rADC) values were calculated and the midline shift (MLS) was measured. A series of histological detection techniques were performed to observe changes in the cerebral cortex and striatum of CIRI rats. Correlation analysis of rADC values with aquaporin-4 (AQP4) and sodium-potassium-chloride cotransport protein 1 (Na+-K+-2Cl-- cotransporter 1; NKCC1) was performed. rADC values began to increase and reached a relatively low value in the cerebral cortex and striatum at 24 h after reperfusion, and the MLS reached relatively high values at 24 h after reperfusion (all p < 0.05). Hematoxylin-eosin (HE) staining showed that the nerve cells in the cortex and striatum of the sham group were regular in morphology and neatly arranged, and in the CIRI-24 h group were irregular, disorganized, and loosely structured. Using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, the number of TUNEL+ cells in the ischemic cortex and striatum in CIRI-24 h group was shown to increase significantly compared with the sham group (p < 0.05). Transmission electron microscopy showed that the perivascular astrocytic foot processes were swollen in the cortex and striatum of the CIRI-24 h group. Pearson correlation analysis demonstrated that rADC values were negatively correlated with the number of anti-glial fibrillary acidic protein (GFAP)+AQP4+ and GFAP+NKCC1+ cells of the CIRI rats. MRI combined with histological techniques can dynamically assess cytotoxic edema after CIRI, in a manner that is clear and intuitive for scientific researchers and clinicians, and provides a scientific basis for the application of MRI techniques for monitoring the dynamic progress of CIRI.

Exploring Immunohistochemistry in Fish: Assessment of Antibody Reactivity by Western Immunoblotting.

In recent years, research on fish has seen remarkable advancements, especially in aquaculture, ornamental fish industry, and biomedical studies. Immunohistochemistry has become crucial in fish research, aiding in physiological and pathological investigations. However, the use of antibodies originally developed for mammals has raised concerns about their cross-reactivity and specificity in fish. This study systematically evaluated the reactivity of commonly used antibodies for diagnostic purposes, especially in fish pathology, including pan-cytokeratin, vimentin, S-100, glial fibrillary acidic protein, and desmin in the tissue of Sparus aurata, Dicentrarchus labrax, Oncorhynchus mykiss, and Carassius auratus. Western immunoblotting was employed to assess antibody specificity. The results revealed that the pan-cytokeratin and glial fibrillary acidic protein antibodies cross-react with all tested fish species, while S-100 demonstrated specific staining in sea bream, goldfish, and rainbow trout tissues. Conversely, vimentin and desmin antibodies displayed no reactivity. In conclusion, the anti-cytokeratin clone AE1/AE3 and the polyclonal rabbit anti-glial fibrillary acidic protein antibody, which are extensively used in mammals, were validated for fish immunohistochemical studies. Regrettably, D33 anti-desmin and V9 anti-vimentin clones are unsuitable for immunohistochemistry in the tested fish. These findings underscore the need for species-specific antibodies and proper validation for accurate immunohistochemistry analyses in fish research.

Peripheral nervous system involvement accompanies central nervous system involvement in anti-glial fibrillary acidic protein (GFAP) antibody-related disease.

Glial fibrillary acidic protein (GFAP) is expressed by astrocytes in the central nervous system (CNS), but also by immature and regenerative Schwann cells in the peripheral nervous system (PNS). GFAP antibodies (GFAP-Abs) in cerebrospinal fluid (CSF) have been mainly described in patients with meningoencephalomyelitis. We aimed to study PNS symptoms in patients with CSF GFAP-Abs. We retrospectively included all patients tested positive for GFAP-Abs in the CSF by immunohistochemistry and confirmed by cell-based assay expressing human GFAPα since 2017, from two French reference centers. In a cohort of 103 CSF GFAP-Abs patients, 25 (24%) presented with PNS involvement. Among them, the median age at onset was 48years and 14/25 (56%) were female. Abnormal electroneuromyography was observed in 11/25 patients (44%), including eight isolated radiculopathies, one radiculopathy associated with polyneuropathy, one radiculopathy associated with sensory neuronopathy, and one demyelinating polyradiculoneuropathy. Cranial nerve involvement was observed in 18/25 patients (72%). All patients except one had an associated CNS involvement. The first manifestation of the disease concerned the PNS in three patients. First-line immunotherapy was administered to 18/24 patients (75%). The last follow-up modified Rankin Scale was ≤ 2 in 19/23 patients (83%). Patients with PNS involvement had significantly more bladder dysfunction than patients with isolated CNS involvement (68 vs 40.3%, p = 0.031). PNS involvement in GFAP-Abs autoimmunity is heterogeneous but not rare and is mostly represented by acute or subacute cranial nerve injury and/or lower limb radiculopathy. Rarely, PNS involvement can be the first manifestation revealing the disease.

The interaction of Schistosoma mansoni infection with diabetes mellitus and obesity in mice

Human schistosomiasis is one of the most prevalent parasitic diseases worldwide. Various host factors can affect the host–parasite interactions. Therefore, the aim of the present work was to determine the parasitological, histopathological, biochemical, and immunological status of Schistosoma mansoni-infected hosts with metabolic disorders to identify the underlying possible mechanisms of these comorbidities. The study animals were divided into four groups. Group I represented the control groups, namely, the normal control group, the S. mansoni-infected control group, and the noninfected type 1 diabetes (T1DM), type 2 diabetes (T2DM), and obesity groups. The mice of the other three groups underwent induction of T1DM (Group II), T2DM (Group III) and obesity (Group IV) before being infected with S. mansoni. All mice were subjected to body weight measurement, blood glucose and insulin assessment, parasitological evaluation of adult worm count, tissue egg count and intestinal oogram. Histopathological and immunohistochemical study using anti-glial fibrillary acidic protein (GFAP) in hepatic stellate cells (HSCs) and image analysis of Masson’s trichrome-stained liver sections using ImageJ (Fiji) software were carried out. Additionally, immunological analysis of tumour necrosis factor (TNF) beta, interleukin-5 (IL-5), IL-10, Forkhead box P3 (FOXP3) and pentraxin 3 (PTX3) levels besides biochemical study of total lipid profile were evaluated. The present study revealed a significant increase in the adult worm count and tissue egg output in the obesity group compared to the infected control group. The oogram of counted eggs showed prevalence of immature eggs in T1DM group, while T2DM and obese groups showed prevalence of mature eggs. The fibrosis area percentage showed significant increase in T2DM and obese groups while it was decreased in T1DM group in comparison to infected control group. Our data also showed significant increase in the levels of TNF-β, IL-5, PTX3 in T1DM, T2DM and obesity groups in comparison to infected control group, whilst the levels of FOXP3 and IL-10 were increased in the infected groups in comparison to their noninfected controls. Moreover, infected T1DM, T2DM and obesity groups showed higher blood glucose and lipid profile in comparison to the infected control group. However, these parameters were improved in comparison to their noninfected controls. In sum, induction of T2DM and obesity increased tissue egg counts, mature egg percentage, and fibrosis density, while schistosome infection induced changes in the lipid profile and blood glucose levels in infected diabetic and obese groups and impacted favorably insulin levels in obese mice. By better understanding the complexities of host–parasite interactions, efforts to reduce the burden of these debilitating diseases can be improved.

Encefalomielitis diseminada aguda, síndrome de Susac y astrocitopatía anti-PGFA

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease more common in children than in adults, often preceded by a nonspecific infectious process. It is typically characterized by encephalopathy and multifocal symptoms and signs and, in some cases, may take a more aggressive form such as acute hemorrhagic leukoencephalitis. A substantial number of patients will be positive for IgG-MOG (especially in children), and to a lesser extent for IgG-AQP4. ADEM is usually monophasic, but recurrent and/or persistent seropositive forms will require chronic immunomodulation. Susac syndrome is an inflammatory endotheliopathy characterized by occlusion of retinal arterial branches, hearing loss and encephalopathy, with no known biomarker and with neuroimaging findings amenable to differential diagnosis with multiple sclerosis. Anti-glial fibrillary acidic protein astrocytopathy (PGFA) can present with meningitis, encephalitis, myelitis, papillitis and epilepsy, is paraneoplastic in a third of cases and has an exquisite response to corticosteroids.

The Coexistence of Antibodies to Neuronal Cell and Synaptic Receptor Proteins, Gangliosides and Selected Neurotropic Pathogens in Neurologic Disorders in Children

Various primarily non-autoimmune neurological disorders occur synchronously with autoantibodies against tissues in the nervous system. We aimed to assess serum and cerebrospinal fluid (CSF) autoantibodies in children with neurologic disorders. To find new diagnostic tools, we compared the laboratory and clinical findings between the distinguished groups. Retrospectively, 508 patients were divided into six subgroups: neuroinfections, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, neurologic autoimmune and demyelinating diseases, epilepsy, pervasive developmental disorders and other patients. We analysed serum anti-aquaporin-4, antiganglioside, neuronal antinuclear and cytoplasmic antibodies, as well as antibodies against surface neuronal and synaptic antigens in the CSF and serum. We involved available demographic and clinical data. Autoantibodies appeared in 165 (32.3%) children, with 24 showing multiple types of them. The most common were anti-neuroendothelium (anti-NET), anti-N-Methyl-D-Aspartate receptor (anti-NMDAr), anti-glial fibrillary acidic protein and anti-myelin antibodies bothering 46/463 (9.9%), 32/343 (9.4%), 27/463 (5.8%) and 27/463 (5.8%), respectively. Anti-NET and anti-NMDAr antibodies appeared more frequently in children with autoimmunity (p = 0.017; p < 0.001, respectively), increasing the autoimmune disease risk (OR = 2.18, 95% CI 1.13-13.97; OR = 3.91, 95% CI 1.86-8.22, respectively). Similar pathomechanisms appeared in diseases of different aetiology with clinical spectrums mimicking each other, so we proposed the model helping to diagnose autoimmune disease. We proved the influence of age, living place and medical history on the final diagnosis.

Small vessel childhood primary angiitis of the central nervous system with positive anti-glial fibrillary acidic protein antibodies: a case report and review of literature

BackgroundSmall vessel childhood primary angiitis of the central nervous system (SV-cPACNS) is a rare disease characterized by inflammation within small vessels such as arterioles or capillaries.Case presentationWe report a case of SV-cPACNS in an 8-year-old boy confirmed by brain biopsy. This patient was also incidentally found to have anti-glial fibrillary acidic protein (GFAP) antibodies in the cerebrospinal fluid (CSF) but had no evidence of antibody-mediated disease on brain biopsy. A literature review highlighted the rarity of SV-cPACNS and found no prior reports of CSF GFAP-associated SV-cPACNS in the pediatric age group.ConclusionWe present the first case of biopsy proven SV-cPACNS vasculitis associated with an incidental finding of CSF GFAP antibodies. The GFAP antibodies are likely a clinically insignificant bystander in this case and possibly in other diseases with CNS inflammation. Further research is needed to determine the clinical significance of newer CSF autoantibodies such as anti-GFAP before they are used for medical decision-making in pediatrics.

Astrocytic Response in the Striatum and Corpus Callosum of the Brain of Adult Wistar Rats with Global Ischaemia

Ischaemic stroke occurs when the blood supply to a part of the brain is suddenly interrupted. Astrocytes are known to maintain ionic homeostasis, scavenge free radicals and support neurogenesis. This study examined the astrocytic responses in the corpus callosum and striatum to global ischaemia with functional deficits in adult male rats. The common carotid artery (CCA) in adult rats was occluded temporarily (30 min) or permanently and then kept for 24 h or three days, while a sham operation was done for the control (n=10 per group). Neurobehavioural testing for motor deficits (square grid and pole tests) were carried out before sacrifice. The rats’ brains were stained with haematoxylin and eosin, and immunohistochemically with anti-glial fibrillary acidic protein for astrocytes. Quantitative data from behavioural tests were compared using analysis of variance, and significance was set at 0.05. The rats with permanent CCA occlusion had increased latency to turn and return to the base in the pole test, and reduced latency to fall in the square grid test compared to the temporary occlusion and control groups. Sections of the corpus callosum and striatum had increased proliferation and hypertrophy of the astrocytes in the permanent CCA occlusion, which was less obvious in the temporary occlusion group compared to the control. Global ischaemia caused neuronal degeneration and reactive astrogliosis in the corpus callosum and striatum, which were more pronounced in the group with permanent arterial occlusion than those that underwent reperfusion. Early reperfusion is crucial for structural and functional recovery following brain ischaemia in stroke management, and astrocytes play important roles in both the pathogenesis and recovery process.

A case of GFAP-IgG positivity followed by anti-NMDAR encephalitis

BackgroundIn recent years, there have been an increasing number of reports on overlapping antibodies in autoimmune encephalitis (AE). There are various types of overlapping antibodies, but the clinical significance of each type is not yet clear. Glial antibodies, such as MOG, AQP4, and especially NMDAR, can be detected in patients with AE. However, little is known about the overlapping antibodies of anti-glial fibrillary acidic protein (GFAP), and only a few case reports have described this overlap.Case presentationThe patient was a 7-year-old girl with recurrent intermittent fever and seizures, and viral encephalitis was diagnosed at the beginning of the disease. She was discharged after treatment with acyclovir, high-dose immunoglobulins, and valproic acid as an antiseizure medication. Subsequently, the patient still had occasional seizures and abnormal behavior, and the anti-NMDAR antibody test was positive (1:3.2). She was treated with high-dose methylprednisolone and antiseizure therapy. Approximately half a year later, the patient experienced fever and seizures again, serum GFAP IgG was 1:100, and a head MRI indicated new lesions. Improvement was achieved after repeated high-dose methylprednisolone and continuous prednisone anti-inflammatory therapy.ConclusionsAnti-NMDAR encephalitis combined with GFAP-IgG is uncommon, and repeated tests for AE-associated antibodies may be required in patients with recurrent encephalitis. Compared with cerebrospinal fluid antibody-positive children, serum GFAP IgG-positive children should be comprehensively diagnosed according to their clinical manifestations. It is worth considering whether overlapping antibody syndrome can still be an issue for patients with AE who recover and have negative antibodies after a few months if disease recurrence and new antibodies are detected.

Investigation of Neurogenesis in Kindled Wistar and Genetic Absence Epilepsy Rats

Objective: The most common type of epilepsy affecting about 50 million people worldwide is temporal lobe epilepsy (TLE). Chemical and electrical kindling methods in animals can be used to form TLE model. In the present study, it was aimed to investigate neurogenesis in the hippocampus of adult kindled Wistar rats and genetic absence epilepsy rats from Strasbourg (GAERS) rats by immunofluorescence methods.&#x0D; &#x0D; Methods: Adult Wistar and GAERS albino rats weighing 250-300 gr were injected pentylenetetrazole (PTZ) (35 mg/kg, s.c.) every other day to produce chemical kindling. Animals having 5 times grade 5 seizures were considered to be kindled. Intracardiac perfusion was performed under deep anesthesia on the 7th and 14th days after the last grade 5 seizure. Immunofluorescence methods were used to demonstrate newly formed neurons, astroglial cells, and mature neurons, by using anti-doublecortin (DCX), anti-glial fibrillary acidic protein (GFAP), and anti- neuronal nuclear antigen (NeuN) primary antibodies, respectively. Sections were then examined under a fluorescence microscope.&#x0D; &#x0D; Results: DCX (+) cells were found to be increased in GAERS control groups compared to the Wistar control groups; and in Wistar PTZ groups compared to the Wistar control groups. DCX (+) cells were decreased in GAERS PTZ groups compared to their controls and to Wistar PTZ groups.&#x0D; &#x0D; Conclusion: The findings of the present study suggest that the resistance to electrical kindling of GAERS reported in previous studies might be related to the increased neurogenesis in this strain.

Experimental Infection of Embryonic Cells and Embryonated Eggs of Cockatiels (Nymphicus hollandicus) with Two Parrot Bornavirus Isolates (PaBV-4 and PaBV-2).

Parrot bornavirus (PaBV) might be transmitted vertically. Cockatiel embryonic brain cells and embryonated eggs of cockatiels (ECE) were infected with PaBV-2 and PaBV-4. In embryonic brain cells, PaBV-2 and PaBV-4 showed no differences in viral spread despite the slower growth of PaBV-2 compared with PaBV-4 in CEC-32 cells. ECE were inoculated with PaBV-4 and 13–14 dpi, organs were sampled for RT-PCR, immunohistochemistry/histology, and virus isolation. In 28.1% of the embryos PaBV-4-RNA and in 81.3% PaBV-4-antigen was detected in the brain. Virus isolation failed. Division of organ samples and uneven tissue distribution of the virus limited the results. Therefore, 25 ECE were inoculated with PaBV-4 (group 1) and 15 ECE with PaBV-2 (group 3) in the yolk sac, and 25 ECE were inoculated with PaBV-4 (group 2) and 15 eggs with PaBV-2 (group 4) in the chorioallantoic membrane to use the complete organs from each embryo for each examination method. PaBV-RNA was detected in the brain of 80% of the embryos in groups 1, 2, 3 and in 100% of the embryos in group 4. In 90% of the infected embryos of group 1, and 100% of group 2, 3 and 4, PaBV antigen was detected in the brain. PaBV antigen–positive brain cells were negative for anti-neuronal nuclear protein, anti-glial fibrillary acidic protein, and anti S-100 staining. Virus was not re-isolated. These results demonstrated a specific distribution pattern and spread of PaBV-4 and PaBV-2 in the brain when inoculated in ECE. These findings support a potential for vertical transmission.

Clinicopathological analysis of secondary retinal vasoproliferative tumor/reactive retinal astrocytic tumor successfully treated by endoresection.

To report the clinicopathological findings of retinal vasoproliferative tumor/reactive retinal astrocytic tumor (VPT/RRAT) with retinal vasculitis, treated by tumor resection. A retrospective single case report. A 29-year-old Japanese woman was referred with cystoid macular edema and retinal vasculitis in the right eye. Best-corrected visual acuity (BCVA) was 0.9. Fundus examination, optical coherence tomography, and fluorescein angiography demonstrated VPT/RRATs in the temporal retina surrounded by a subretinal exudate, serous retinal detachment and macular edema, and retinal vasculitis. Despite 3 months of oral prednisolone treatment, a full-thickness macular hole developed. Pars plana vitrectomy and endoresection of the VPT/RRATs were performed. Pathological and immunohistochemical analyses with anti-CD34 antibody, anti-glial fibrillary acidic protein (GFAP) antibody, anti-Ki67 antibody, and anti-vascular endothelial growth factor (VEGF) antibody were conducted on the excised tissue. Inflammation was evaluated by immunohistological staining with leucocyte common antigen (LCA), anti-CD3 antibody, and anti-CD20 antibody. After surgery, the macular hole closed, BCVA improved to 1.2, retinal vasculitis was ameliorated, and retinal exudate disappeared. There was no recurrence of VPT/RRAT or retinal vasculitis. Pathological examination showed that GFAP and VEGF were widely expressed, irrespective of the distribution of blood vessels. Ki67-positive proliferating cells were detected in the perivascular area. LCA-positive leukocytes and CD3-positive T cells were detected throughout the samples, whereas CD20-positive B cells were rarely detected. Endoresection of VPT/RRAT could be a good treatment option for secondary VPT/RRAT accompanied by retinal vasculitis. Pathological findings revealed for the first time that inflammatory cells infiltrate the tissue in secondary VPT/RRAT.

Update in autoimmune and paraneoplastic myelopathies: Newly described antigen targets and antibody testing.

Myelopathy is an increasingly recognized presentation of many antibody-mediated neuroinflammatory disorders. While specific features of certain autoimmune myelopathies such as aquaporin-4 antibody associated neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein associated disorder (MOGAD) are well-characterized, other less commonly seen antibody-associated myelopathies are not as well-defined. These include but are not limited to, Hu/ANNA1, anti-glial fibrillary acidic protein (GFAP), anti-CV2/collapsin response mediator protein (CRMP5), and amphiphysin. Here, we review the mentioned more common antibody mediated myelopathies as well those that as less common, followed by a review of differentials that may mimic these disorders.

Brain-Reactive Antibodies are Potential Biomarkers for Evaluating Therapeutic Efficacy in NPSLE Patients.

PurposeNeuropsychiatric systemic lupus erythematosus (NPSLE) is the main cause of disability and death in systemic lupus erythematosus (SLE). It can cause cognitive impairment and organic brain syndrome. Brain-reactive antibodies, such as anti-DNA/anti-N-methyl-D-aspartate receptor (NMDAR) antibodies (DNRAbs), anti-microtubule-associated protein 2 (anti-MAP2) antibodies, and anti-glial fibrillary acidic protein (anti-GFAP) antibodies are thought to participate in the progression of NPSLE and thus considered potential diagnostic biomarkers, but whether they can be used for evaluating therapeutic efficacy in NPSLE is unknown.Patients and methodsOverall, 17 NPSLE patients and 10 non-SLE controls were included in this study. All the patients were treated with glucocorticoid (GC) pulse therapy. Serum and cerebrospinal fluid (CSF) concentrations of DNRAbs and anti-MAP2 and anti-GFAP antibodies were measured using enzyme-linked immunosorbent assay. The differences between the CSF concentrations of these antibodies in NPSLE patients before and after GC pulse therapy were analyzed.ResultsCSF concentrations of DNRAbs and anti-MAP2 and anti-GFAP antibodies were significantly higher in NPSLE patients compared to the non-SLE controls. Among the patients, CSF concentration of DNRAbs was significantly higher in the patients with acute confusional state (ACS) than in those with non-ACS diffuse NPSLE or focal NPSLE. Additionally, CSF concentration of DNRAbs was significantly correlated with QIgG (r=0.4884, P=0.0467) and IgG index (r=0.5319, P=0.0280) in NPSLE patients. Moreover, CSF concentrations of DNRAbs, anti-MAP2, and anti-GFAP antibodies and QIgG were significantly decreased after GC pulse therapy in NPSLE patients.ConclusionThese results indicate that CSF DNRAbs and anti-MAP2 and anti-GFAP antibodies are potential biomarkers for evaluating therapeutic efficacy in NPSLE.

The Clinical Spectrum of Autoimmune-Mediated Neurological Diseases in Paediatric Population.

Neurological autoimmune diseases have various origins and pathogeneses. Specific antibodies are associated with paraneoplastic syndromes, other infectious agents, or inherited disorders. We aim to evaluate the relation between the autoantibodies, the chosen symptoms, demographic characteristics, and infection history. We retrospectively analysed 508 children during neurological diagnostics. We investigated serum antineuronal, IgG, IgM anti-ganglioside, and anti-aquaporin-4 in both the serum and cerebrospinal fluid (CSF) anti-cell surface and anti-synaptic protein antibodies in 463, 99, 44, 343, and 119 patients, respectively. The CSF polymerase chain reaction detection of Herpesviridae, enterovirus, B19 parvovirus, adenovirus, and parechovirus involved 261 patients. We included available clinical information and electroencephalographic, radiologic, and microbiological results. The IgM anti-ganglioside antibodies increased the risk of tics and positive symptoms (p = 0.0345, p = 0.0263, respectively), the anti-glutamic acid decarboxylase particle of paresis (p = 0.0074), and anti-neuroendothelium of mutism (p = 0.0361). Anti-neuroendothelium, IgM anti-ganglioside, and CSF anti-N-methyl-D-aspartate antibodies were more often associated with consciousness loss (p = 0.0496, p = 0.0044, p = 0.0463, respectively). Anti-myelin antibodies co-occured with Herpes simplex virus (HSV)-2 IgG (p = 0.0415), anti-CV2 with HSV-1 IgM (p = 0.0394), whereas anti-glial fibrillary acidic protein was linked with past Epstein-Barr virus infection. The anti-ganglioside IgM and anti-myelin particles were bilaterally correlated (p = 0.0472). The clinical pictures may overlap, requiring specialistic diagnostics. We noticed the links between the infection aetiology and the specific autoantibody’s positivity.