scholarly journals Neurologic syndromes related to anti-GAD65

2020 ◽  
Vol 7 (3) ◽  
pp. e696 ◽  
Author(s):  
Amaia Muñoz-Lopetegi ◽  
Marienke A.A.M. de Bruijn ◽  
Sanae Boukhrissi ◽  
Anna E.M. Bastiaansen ◽  
Mariska M.P. Nagtzaam ◽  
...  

ObjectiveAntibodies against glutamic acid decarboxylase 65 (anti-GAD65) are associated with a number of neurologic syndromes. However, their pathogenic role is controversial. Our objective was to describe clinical and paraclinical characteristics of anti-GAD65 patients and analyze their response to immunotherapy.MethodsRetrospectively, we studied patients (n = 56) with positive anti-GAD65 and any neurologic symptom. We tested serum and CSF with ELISA, immunohistochemistry, and cell-based assay. Accordingly, we set a cutoff value of 10,000 IU/mL in serum by ELISA to group patients into high-concentration (n = 36) and low-concentration (n = 20) groups. We compared clinical and immunologic features and analyzed response to immunotherapy.ResultsClassical anti–GAD65-associated syndromes were seen in 34/36 patients with high concentration (94%): stiff-person syndrome (7), cerebellar ataxia (3), chronic epilepsy (9), limbic encephalitis (9), or an overlap of 2 or more of the former (6). Patients with low concentrations had a broad, heterogeneous symptom spectrum. Immunotherapy was effective in 19/27 treated patients (70%), although none of them completely recovered. Antibody concentration reduction occurred in 15/17 patients with available pre- and post-treatment samples (median reduction 69%; range 27%–99%), of which 14 improved clinically. The 2 patients with unchanged concentrations showed no clinical improvement. No differences in treatment responses were observed between specific syndromes.ConclusionMost patients with high anti-GAD65 concentrations (>10,000 IU/mL) showed some improvement after immunotherapy, unfortunately without complete recovery. Serum antibody concentrations' course might be useful to monitor response. In patients with low anti-GAD65 concentrations, especially in those without typical clinical phenotypes, diagnostic alternatives are more likely.

Author(s):  
Ema Grilo ◽  
Joana Pinto ◽  
Joana Serra Caetano ◽  
Helena Pereira ◽  
Patrícia Cardoso ◽  
...  

AbstractLimbic encephalitis is a rare neurological disorder that may be difficult to recognize. Clinical features include memory impairment, temporal lobe seizures and affective disturbance. We report the case of a 10-year-old girl with type 1 diabetes mellitus that presented with seizures, depressed mood and memory changes. The diagnosis of glutamic acid decarboxylase 65 (GAD65) mediated limbic encephalitis relied on cerebral magnetic resonance imaging lesions and high serological and cerebrospinal fluid GAD65-antibodies titers. High-dose steroidal therapy was started with clinical improvement. Relapse led to a second high-dose steroid treatment followed by rituximab with remission. A correlation between serum GAD65-antibodies levels and symptoms was found, demonstrating GAD65-antibodies titers may be useful for clinical follow-up and immunotherapy guidance. This report raises awareness of this serious neurological condition that may be associated with type 1 diabetes, underlining the importance of an early diagnosis and prompt treatment for a better prognosis.


2020 ◽  
pp. 10.1212/CPJ.0000000000000939
Author(s):  
Emily J. Hill ◽  
Joseph Jankovic

Autoimmune and paraneoplastic movement disorders are increasingly recognized as a result of improved methods in detecting antibodies directed against intracellular, membrane, and other antigens.1 High concentrations of anti-glutamic acid decarboxylase 65 (GAD65) antibodies are associated with several neurologic syndromes including stiff-person syndrome, epilepsy, limbic encephalitis, and cerebellar ataxia.2 Anti-GAD65-associated cerebellar ataxia is typically generalized with prominent gait disturbance and eye movement abnormalities.1 Limb ataxia is present in 60-70% of patients.3 Here we present 2 unusual cases of hemiataxia associated with high concentrations of anti-GAD65 antibodies.


Author(s):  
Maude-Marie Gagnon ◽  
Martin Savard

AbstractRecently, many cases of autoimmune limbic encephalitis with positive GAD65 (glutamic acid decarboxylase) antibodies have been described in the scientific literature. However, it remains an understudied topic of great relevance to practicing neurologists. Thus, we report here a review of published cases, in English, of autoimmune limbic encephalitis with this type of antibodies, focusing on presenting symptoms and signs, associated conditions, and findings upon investigation. We also report treatment responses. We aim to offer a better description of the clinical spectrum of autoimmune limbic encephalitis associated with GAD65 antibodies as well as to expose its paraclinical features and outcome.


Author(s):  
Yasuyoshi Fukuda ◽  
Misako Higashiya ◽  
Takahiro Obata ◽  
Keita Basaki ◽  
Megumi Yano ◽  
...  

Abstract To cryopreserve cells, it is essential to avoid intracellular ice formation during cooling and warming. One way to achieve this is to convert the water inside the cells into a non-crystalline glass. It is currently believed that to accomplish this vitrification, the cells must be suspended in a very high concentration (20–40%) of a glass-inducing solute, and subsequently cooled very rapidly. Herein, we report that this belief is erroneous with respect to the vitrification of one-cell rat embryos. In the present study, one-cell rat embryos were vitrified with 5 μL of EFS10 (a mixture of 10% ethylene glycol, 27% Ficoll, and 0.45 M sucrose) in cryotubes at a moderate cooling rate, and warmed at various rates. Survival was assessed according to the ability of the cells to develop into blastocysts and to develop to term. When embryos were vitrified at a 2,613 °C/min cooling rate and thawed by adding 1 mL of sucrose solution (0.3 M, 50 °C) at a warming rate of 18,467 °C/min, 58.1 ± 3.5% of the EFS10-vitrified embryos developed into blastocysts, and 50.0 ± 4.7% developed to term. These rates were similar to those of non-treated intact embryos. Using a conventional cryotube, we achieved developmental capabilities in one-cell rat embryos by rapid warming that were comparable to those of intact embryos, even using low concentrations (10%) of cell-permeating cryoprotectant and at low cooling rates.


1973 ◽  
Vol 44 (2) ◽  
pp. 163-179 ◽  
Author(s):  
Anne M. S. Grant ◽  
A. Neuberger

1. A specific and quantitative radioimmunoassay was developed for the measurement of low concentrations of human and rabbit Tamm—Horsfall glycoprotein in the presence of other proteins. Antibody-coated tubes were used as a solid phase in the assay and the optimum antibody concentration and duration of antibody coating were established. 2. Pure Tamm—Horsfall glycoprotein was labelled with 125I and, because of its apparent susceptibility to radiation damage, was labelled at weekly intervals. 3. Sodium dodecyl sulphate, an ionic detergent, was included in the assay at a final concentration of 0.0005% to disaggregate the glycoprotein. An overnight preincubation step in the presence of the detergent was necessary before the disaggregated glycoprotein solutions were allowed to react with the antibody. Pretreatment of the tracer with detergent was not necessary. 4. Two glycoprotein standards were prepared fresh for each assay from freeze-dried material. The average linear range of the assay was between approx. 150 ng/ml and 2.5 μg/ml. Albumin was only shown to interfere with the assay at concentrations greater than 100 μg/ml. 5. Urines were dialysed against water for 3 days before assay to remove inhibitory material. Urines were never frozen as this was found to affect the assay. 6. A recovery experiment showed that the pure freeze-dried standard behaved in an immunologically identical way to the urinary glycoprotein. 7. Human Tamm-Horsfall glycoprotein cross-reacted with guinea-pig anti-(rabbit Tamm—Horsfall) antiserum and rabbit Tamm—Horsfall glycoprotein cross-reacted with guinea-pig anti-(human Tamm—Horsfall) antiserum, but not with rabbit anti-(human Tamm—Horsfall) antiserum. This showed a partial immunological identity between Tamm-Horsfall glycoprotein from humans and rabbits which was only evident when the antiserum was raised in a third species. 8. The excretion rate of Tamm—Horsfall glycoprotein in normal humans was found to be 48.1 ± 9.6 (SD) mg/24 h for males and 50.5 ± 14.8 (SD) mg/24 h for females. The mean excretion rate of the glycoprotein in New Zealand White rabbits was 34.8 ± 7.9 mg/24 h.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 813
Author(s):  
Cynthia B. Van Van Landingham ◽  
Debra R. Keast ◽  
Matthew P. Longnecker

Treatment with prebiotics, a type of dietary fiber, was recently shown to increase antibody concentrations following influenza vaccination in a meta-analysis of clinical trials. In observational epidemiologic studies it is not possible to estimate intake of prebiotics, but quantifying intake of dietary fiber is routine. Our objective was to investigate the potential effect of dietary fiber on immunogenicity. We examined serum antibody concentrations (Measles, Mumps, Rubella, and Varicella) in relation to dietary fiber in more than 12,000 subjects in the U.S. National Health and Nutrition Examination Survey (NHANES) for the period 1999–2004. Data from one (1999–2002) or two (2003–2004) dietary recalls were used to calculate fiber intake. For Mumps the adjusted percentage difference in antibody concentration per interquartile range intake in energy-adjusted dietary fiber was 6.34% (95% confidence interval, 3.10, 9.68). Fiber from grain-based foods was more positively associated than fiber from other fiber-containing food groups. The association was slightly larger among subgroups with higher fiber intake, greater interquartile range in fiber intake, and less measurement error. Furthermore, based on the reliability of the diet recalls in 2003–2004, we calculated that the percentage difference per interquartile increment was substantially attenuated by measurement error. Dietary fiber may have a favorable influence on the immunogenicity of some vaccines or natural infections.


PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_1) ◽  
pp. 252-254
Author(s):  
Georges Peter

One hundred forty-one children of 5 to 59 months of age were immunized with a single intramuscular dose of 0.67, 3.3, 17, or 67 μg polyribophosphate (PRP), the capsular antigen ofHemophilus influenzae, type b. The immunizations were well tolerated, particularly at doses of .67 to 17 μg. Antibody activity was measured by radioactive antigen binding, using3H-labelled PRP. Doses of 3.3 and 17 μg produced significant antibody rises in nearly 90% of recipients; 0.67 and 67 μg in approximately half. The geometric mean titers were similar at three and six weeks after immunization and were greater with the middle doses. The net antibody increase in responding children was strongly age dependent, but was not related to the preimmunization antibody concentration. Rises in serum bactericidal activity against H. influenzae type b generally accompanied rises in antibody concentration as measured by the antigen-binding assay. A recently developed Haemophilus influenzae type b capsular polysaccharide vaccine was given to 48 977 children 3 months to 5 years of age; an equal number of children receiving group A meningococcal vaccine served as controls. The protection as well as serum antibody response was strongly age dependent. Among children who had received the H. influenzae type b vaccine when 18 months of age or older, there were no cases of bacteremic disease caused by H. influenzaetype b in the first year after vaccination. At the same time 11 such cases were seen in the control group of the same age, a highly significant difference. In the second year after vaccination two cases occurred in the H. influenzae type b-vaccinated group, five in the meningococcal-group A vaccinated group. No protection was seen among children who had been younger than 18 months when vaccinated, even if they received a booster dose of the vaccine. The serum antibody response to the H. influenzae type b polysaccharide, measured by radioimmunoassay, was poor in children below 18 months of age and good in those above it. No effect of the vaccine could be seen on the nasopharyngeal carriage of H. influenzae type b, which was approximately 6% in this age group. Adverse effects of the vaccine were mild.


1975 ◽  
Vol 18 (1) ◽  
pp. 113-121
Author(s):  
R.M. Rizki ◽  
T.M. Rizki ◽  
C.A. Andrews

The effects of wheat germ agglutinin on Drosophila embryonic cell lines growing on cover-glasses was examined by scanning electron microscopy. At low concentrations of the lectin (5-10 mug/ml), cells spread against the glass surface and fused to form syncytia. At high concentration, damage to the cell surface was evidenced as extensive membrane shrivelling and loss of surface microfilaments. Fusion also occurred under these conditions. There was some indication that the morphology of cells in division remains undisturbed by wheat germ agglutinin. The coalescence of cells and morphologic disotrtion induced by wheat germ agglutinin were not inhibited by N-acetylglucosamine, the hapten inhibitor of the lectin, under the conditions utilized in this study.


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