Autopsy Case of Meningoencephalomyelitis Associated With Glial Fibrillary Acidic Protein Antibody

Background and ObjectivesTo describe the autopsy findings and neuropathologic evaluation of autoimmune meningoencephalomyelitis associated with glial fibrillary acidic protein (GFAP) antibody.MethodsWe reviewed the clinical course, imaging, laboratory, and autopsy findings of a patient with autoimmune meningoencephalomyelitis associated with GFAP antibody who had a refractory course to multiple immunosuppressive therapies.ResultsThe patient was a 70-year-old man who was diagnosed as GFAP antibody-associated autoimmune meningoencephalomyelitis. MRI of the head showed linear perivascular enhancement in the midbrain and the basal ganglia. Despite treatment with high-dose corticosteroids, plasma exchange, IV immunoglobulins, and cyclophosphamide, he died with devastating neurologic complications. Autopsy revealed a coexistent neuroendocrine tumor in the small intestine and diffuse inflammation in the brain parenchyma, perivascular spaces, and leptomeninges, with predominant T-cells, macrophages, and activated microglia. B-cells and plasma cells were absent. There was no astrocyte involvement with change in GFAP immunostaining.DiscussionThis case illustrates autoimmune meningoencephalomyelitis associated with GFAP antibody in the CSF and coexistent neuroendocrine tumor. The autopsy findings were nonspecific and did not demonstrate astrocyte involvement. Further accumulation of cases is warranted to delineate the utility and pathogenic significance of the GFAP autoantibody.

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079 Glial fibrillary acidic protein (GFAP) astrocytopathy associated with cerebral micro-infarction and poor therapeutic response

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-anzan.67 ◽

2019 ◽

Vol 90 (e7) ◽

pp. A25.2-A25 ◽

Cited By ~ 1

Author(s):

Allycia MacDonald ◽

James Triplett ◽

Srimathy Vijayan ◽

Michael Bynevelt ◽

Rahul Lakshmanan ◽

...

Keyword(s):

White Matter ◽

Glial Fibrillary Acidic Protein ◽

Early Recognition ◽

Oral Intake ◽

Brain Biopsy ◽

Acidic Protein ◽

Gait Disturbance ◽

High Dose ◽

Elevated Protein ◽

Upper Thoracic

IntroductionGlial fibrillary acidic protein (GFAP) astrocytopathy is a lesser recognised immune-mediated meningo-encephalomyelitis, which is steroid responsive in the majority of cases. Neuroimaging is unique with a distinctive symmetric white matter perivascular linear and punctate enhancement pattern. We present a case with classical phenotype but delayed clinical response, and highlight the importance of early recognition and treatment.CaseA 59-year-old Caucasian female presented with a two month history of headache, gait disturbance, insomnia, agitation, disorientation and reduced oral intake. Examination revealed a high frequency upper limb tremor, hypertonicity and pathologically brisk reflexes with impaired cognitive function. MRI brain and spinal cord demonstrated high T2 signal and striking perivascular and punctate enhancement in supratentorial white matter, cervical and upper thoracic cord. CSF examination revealed lymphocytic pleocytosis and elevated protein. Brain biopsy demonstrated reduced GFAP expression, perivascular T-lymphocytic infiltrate, and recent white matter microinfarction. CSF and serum GFAP antibodies were positive.Motor deterioration accompanied progression to a stuporous state. High dose corticosteroids were commenced, followed by intravenous immunoglobulin and mycophenolate. While there was marked improvement of perivascular contrast enhancement on imaging, the patient continued to demonstrate prominent tremor, gait disturbance and behavioural issues 9 months following symptom onset.ConclusionsThe persistence of disability in this case is likely the result of axonal loss from the initial insult, reflected by the biopsy evidence of microinfarction. Awareness of the unique pattern on MRI and the clinical phenotype will aid in early recognition and prompt treatment of this condition, thus preventing the potential long term morbidity.

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Cranioplasty Reverses Dysfunction of the Solutes Distribution in the Brain Parenchyma After Decompressive Craniectomy

Neurosurgery ◽

10.1093/neuros/nyaa028 ◽

2020 ◽

Vol 87 (5) ◽

pp. 1064-1069 ◽

Cited By ~ 2

Author(s):

Alin Borha ◽

Audrey Chagnot ◽

Romain Goulay ◽

Evelyne Emery ◽

Denis Vivien ◽

...

Keyword(s):

Decompressive Craniectomy ◽

Early Time ◽

Brain Parenchyma ◽

Late Time ◽

Perivascular Spaces ◽

Early Time Point ◽

The Impact ◽

The Brain ◽

Brain Homeostasis ◽

Time Point

Abstract Background Solutes distribution by the intracranial cerebrospinal fluid (CSF) fluxes along perivascular spaces and through interstitial fluid (ISF) play a key role in the clearance of brain metabolites, with essential functions in maintaining brain homeostasis. Objective To investigate the impact of decompressive craniectomy (DC) and cranioplasty (CP) on the efficacy of solutes distribution by the intracranial CSF and ISF flux. Methods Mice were allocated in 3 groups: sham surgery, DC, and DC followed by CP. The solutes distribution in the brain parenchyma was assessed using T1 magnetic resonance imaging after injection of DOTA-Gadolinium in the cisterna magna. This evaluation was performed at an early time point following DC (after 2 d) and at a later time point (after 15 d). We evaluated the solutes distribution in the whole brain and in the region underneath the DC area. Results Our results demonstrate that the global solutes distribution in the brain parenchyma is impaired after DC in mice, both at early and late time-points. However, there was no impact of DC on the solutes distribution just under the craniectomy. We then provide evidence that this impairment was reversed by CP. Conclusion The solute distribution in the brain parenchyma by the CSF and ISF is impaired by DC, a phenomenon reversed by CP.

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Differential patterns of glial fibrillary acidic protein-immunolabeling in the brain of adult lizards

The Journal of Comparative Neurology ◽

10.1002/cne.10781 ◽

2003 ◽

Vol 464 (2) ◽

pp. 159-171 ◽

Cited By ~ 9

Author(s):

Samir Ahboucha ◽

Abdelhadi Laalaoui ◽

Marianne Didier-Bazes ◽

Michelle Montange ◽

Howard Michael Cooper ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Acidic Protein ◽

The Brain

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Developmental Changes of S-100 Protein and Glial Fibrillary Acidic Protein in the Brain in Down Syndrome

Experimental Neurology ◽

10.1006/exnr.1993.1052 ◽

1993 ◽

Vol 120 (2) ◽

pp. 170-176 ◽

Cited By ~ 43

Author(s):

Takashi Mito ◽

Laurence E. Becker

Keyword(s):

Down Syndrome ◽

Glial Fibrillary Acidic Protein ◽

Acidic Protein ◽

Developmental Changes ◽

S 100 ◽

The Brain

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P-glycoprotein is strongly expressed in the luminal membranes of the endothelium of blood vessels in the brain

Biochemical Journal ◽

10.1042/bj3260539 ◽

1997 ◽

Vol 326 (2) ◽

pp. 539-544 ◽

Cited By ~ 155

Author(s):

Édith BEAULIEU ◽

Michel DEMEULE ◽

Lucian GHITESCU ◽

Richard BÉLIVEAU

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Western Blotting ◽

Plasma Membranes ◽

Collagen Iv ◽

Acidic Protein ◽

Brain Capillary ◽

P Glycoprotein ◽

Cell Plasma ◽

Capillary Endothelial Cells ◽

The Brain

Luminal membranes of the vascular endothelium were isolated from brain, heart and lungs by modification of their density. The presence of P-glycoprotein (P-gp) was detected by Western blotting in luminal membranes from the endothelium of the three tissues. Strong enrichment in brain capillary luminal membranes, compared with brain capillaries (17-fold) and whole membranes (400–500-fold), indicates that P-gp is mainly located on the luminal side of the brain endothelium. Western blotting was also performed with antibodies directed against GLUT1, glial fibrillary acidic protein, adaptin, IP3R-3, integrins αv and collagen IV as controls to determine whether the preparations were contaminated by other membranes. Strong enrichment of GLUT1 in brain capillary luminal membranes (9.9-fold) showed that the preparation consisted mainly of endothelial cell plasma membranes. Poor enrichment of glial fibrillary acidic protein (1.4-fold) and adaptin (2.4-fold) and a decreased level of IP3R-3, integrins αv and collagen IV excludes the possibility of major contamination by astrocytes or internal and anti-luminal membranes. High levels of P-gp in the luminal membranes of brain capillary endothelial cells suggests that it may play an important role in limiting the access of anti-cancer drugs to the brain.

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