Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy in Children: A Retrospective Analysis of 35 Cases

ObjectiveTo analyze the clinical manifestations, imaging, electroencephalography, treatment, and prognosis of 35 cases of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) in children.MethodsChildren hospitalized in the Department of Neurology, Hunan Children’s Hospital, China, between January 2015 and June 2021, owing to autoimmune diseases of the central nervous system were subjected to a cell-based assay (CBA). The assay identified 40 children positive for GFAP-immunoglobulin (Ig)G antibodies in the serum and/or the cerebrospinal fluid. Based on clinical manifestations and imaging characteristics, five children who were only positive for GFAP-IgG antibodies in serum were excluded, and the remaining 35 children were diagnosed with autoimmune GFAP-A. The clinical data derived from the 35 children were retrospectively analyzed.ResultsA total of 35 children, including 23 males and 12 females with a mean age of 6.3 ± 0.6 years, manifested clinical symptoms of fever (62.9%), headache (42.9%), convulsions (42.9%), abnormal mental behavior (51.4%), disorders of consciousness (54.3%), visual disturbance (22.9%), ataxia (11.4%), paralysis (40%), and autonomic dysfunction (25.7%). One child exhibited only the clinical symptom of peripheral facial nerve palsy. Eleven out of 35 children were also positive for other antibodies. In addition to the common overlapping autoimmune syndromes, one case of autoimmune GFAP-A also manifested as Bickerstaff’s brainstem encephalitis. Linear periventricular enhancement upon MRI was significantly less frequent in children (8.5%) than in adults. In pediatric patients, MRI contrast enhancement was principally seen in the meninges and brain lobes. Although repeated relapse (17.1%) and sequelae symptoms (20%) occurred in some cases, most children showed a favorable prognosis. Spearman’s rank correlation showed that the antibody titer was not significantly associated with the severity of the initial disease conditions.ConclusionsThe disease diagnosis in children seropositive for GFAP antibodies only should receive a comprehensive diagnosis based on their clinical symptoms, imaging, electroencephalographic characteristics, and treatment responses. Some patients with relapses should receive repeated gamma globulin and corticosteroid therapy or the addition of immunosuppressants to their therapeutic regimen, and slow-dose tapering of corticosteroids and extended treatment are recommended for patients with overlapping autoimmune syndromes.

Advanced Magnetic Resonance Imaging (MRI) Characterization in Bickerstaff's Brainstem Encephalitis

Purpose Bickerstaff's brainstem encephalitis(BBE) is considered a scarce variant of Miller-Fisher syndrome(MFS) and Guillain–Barré syndrome (GBS) but accounts for a significant proportion of brainstem encephalitis.Detailed knowledge of their neuroimaging manifestations is of paramount importance for a correct early diagnosis and proper management of the affected patients.In this study,We sought to characterize neuroimaging findings,including the morphology and manifestation of advanced MR imaging and differential diagnosis.Methods Seven BBE patients (5 males,2 females; mean age 42.5 ± 5.7 years,range 17 to 63 years) were retrospectively studied using conventional MRI (T1- and T2- weighted,FLAIR sequences,postcontrast T1-weighted images) and advanced MRI such as diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS).The apparent diffusion coefficient (ADC) values and the MRS ratio were calculated in lesion regions.Results1. The distribution of these lesions typically include bilateral and symmetrical involvement of the mesencephalon,thalamus,tegmentum,infratentorial periaqueductal region,and the periventricular region surrounding the third and fourth ventricles involving white and gray matter; additional supratentorial white matter is not involved.2. MRI axial T2-weighted images and FLAIR sequences showed nearly symmetrical hyperintense signal changes with slightly spotty,patchy,or confluent homogeneous enhancement on postcontrast T1-weighted images without necrosis or hemorrhage.3. DWI signal was enhanced,and the apparent diffusion coefficient (ADC) map signal was slightly increased.ADC values of BBE lesions were in the range of 1.21 to 1.67 × 10−3 mm/s2 (mean 1.38 ± 0.66 × 10−3 mm/s2).4. Proton MR spectrum showed a slight increase in choline and a relative decrease in NAA peak,while Lipid and Lac doublet were not detected.Conclusion Advanced MRI imaging can provide important physiological and metabolic information of BBE and complement the morphological findings of the clinical conventional MRI.

First report of Bickerstaff’s brainstem encephalitis caused by Salmonella Dublin: a case report

Background Diseases caused by nontyphoid Salmonella can range from mild, to self-limiting gastroenteritis and severe invasive infection. Relatively rarely, Salmonella may cause severe encephalopathy. Case presentation We report a suspected case of Bickerstaff’s brainstem encephalitis caused by Salmonella Dublin. A young man presented with impaired consciousness, ataxia, dysarthria, limb weakness, and restricted eyeball abduction. His clinical symptoms were consistent with Bickerstaff’s brainstem encephalitis. Conclusions This is the first case report of Bickerstaff’s brainstem encephalitis caused by Salmonella Dublin in the literature. After treatment, he recovered and was discharged. Early antibiotic treatment of sepsis may control the disease and avoid serious encephalopathy.

Rhombencephalitis due to Listeria monocytogenes infection with GQ1b antibody positivity and multiple intracranial hemorrhage: a case report and literature review

Listeria monocytogenes is a Gram-positive facultative intracellular bacterium that causes central nervous system infection. We report a case of rhombencephalitis caused by L. monocytogenes infection, which mimicked Bickerstaff’s brainstem encephalitis, and GQ1b antibody positivity and multiple intracranial foci were observed. A 68-year-old male patient presented with a nonspecific prodrome of faintness, forehead tightness, and walking instability. This was followed by progressive cranial nerve palsies, limb weakness, cerebellar signs, hyperpyrexia, and impaired consciousness. Brain imaging showed multiple abnormal brainstem and cerebellar signals that were accompanied by blood infiltration without any lesion enhancement. Serum GQ1b antibody positivity led to an initial diagnosis of Bickerstaff’s brainstem encephalitis, which was treated with immunosuppressive therapy with limited efficacy. A pathogen examination helped confirm L. monocytogenes infection. A combination of meropenem and trimethoprim-sulfamethoxazole therapy was applied and the patient recovered without sequelae. The symptoms and imaging of Listeria rhombencephalitis are nonspecific. Accurate diagnosis and prompt treatment of this condition are essential. Whether Listeria infection triggers an autoimmune response remains unclear.

Mother and son cases of Bickerstaff’s brainstem encephalitis and fisher syndrome with serum anti-GQ1b IgG antibodies: a case report

Background Bickerstaff’s brainstem encephalitis (BBE) and Fisher syndrome (FS) are immune-mediated diseases associated with anti-ganglioside antibodies, specifically the anti-GQ1b IgG antibody. These two diseases potentially lie on a continuous spectrum with Guillain-Barré Syndrome (GBS). There are some reports of family cases of GBS and fewer of FS. However, there are no reports of family cases of BBE and FS. Case presentation We report a familial case of an 18-year-old son who had BBE and his 52-year-old mother diagnosed with FS within 10 days. The son showed impaired consciousness 1 week after presenting with upper respiratory symptoms and was brought to our hospital by his mother. He showed decreased tendon reflexes, limb ataxia, albuminocytologic dissociation in his spinal fluid, and positive serum anti-GQ1b antibodies. Haemophilus influenzae was cultured from his sputum. He was diagnosed with BBE and treated with intravenous immunoglobulin (IVIg) therapy, which led to an improvement in symptoms. The mother presented with upper respiratory symptoms 3 days after her son was hospitalized. Seven days later, she was admitted to the hospital with diplopia due to limited abduction of the left eye. She showed mild ataxia and decreased tendon reflexes. Her blood was positive for anti-GQ1b antibodies. She was diagnosed with FS and treated with IVIg, which also led to symptomatic improvement. Conclusions There are no previous reports of familial cases of BBE and FS; therefore, this valuable case may contribute to the elucidation of the relationship between genetic predisposition and the pathogenesis of BBE and FS.

A brief review of the neurological manifestations of the coronavirus disease

Introduction It has been demonstrated experimentally that the coronavirus can enter the central nervous system through olfactory nerves and can even reach medulla. Neurological manifestations are observed more frequently in patients with coronavirus disease. Main text The aim of the review is to seek evidence for infection of the nervous system by the human coronavirus and study the neurological manifestations of the coronavirus and its treatment. A search was done in PubMed, Google Scholar, CrossRef, and Scopus. There is evidence for the coronavirus infection of the nervous system from experimental studies, autopsy reports, and clinical studies. The virus can damage the nervous system either by direct viral damage to the neural cells or by immunopathology. Cerebral edema, neuronal degeneration, encephalitis, meningoencephalitis, acute disseminated encephalomyelitis, Guillain–Barré Syndrome, Bickerstaff’s brainstem encephalitis, Miller Fisher syndrome, polyneuritis, toxic encephalopathy, and stroke can occur. The coronavirus has been demonstrated in the cerebrospinal fluid by polymerase chain reaction technique in infected patients. The abnormalities of the coagulation system increase the risk of cerebrovascular disease. Chloroquine analogs, lopinavir/ritonavir combination, remdesivir, dexamethasone, and immunoglobulin have been shown to be useful for the treatment. Conclusion There is substantial evidence for infection of the nervous system by the different strains of the human coronavirus. The coronavirus enters the nervous system either by the blood or from the olfactory nerves. The neurological diseases correlate with the severity of the coronavirus disease. The treatment is mainly supportive. The reports of patients with encephalitis, encephalomyelitis, and brainstem encephalitis show slow recovery. But a stroke has a high mortality.