Article Figures & Data
Figures
- Figure 1 Comparison of laboratory techniques
ELISA concentrations of serum (A and B) and CSF (A and D) of patients with neurologic disorders in comparison to IHC and CBA. Patients identified with dark gray and yellow squares in A showed a neuropil staining on IHC, instead of the typical GAD pattern. Samples with a neuropil staining and high ELISA concentration had a positive GAD65-CBA result, whereas CBA was negative for low-concentration samples (A). In B and D, dark gray and yellow dots are used in both IHC and CBA columns to identify these samples. In the dark gray dotted patients, a different antibody was found. Serum or CSF of the yellow dotted patients showed a neuropil staining, but no known antibody was found. Serum results from patients with antibody testing for diabetes (DM-1) are shown (C). Logarithmic transformation was used for charts. Concordance rates for ELISA, IHC, and CBA are provided for serum and CSF (E). CBA = cell-based assay; GAD = glutamic acid decarboxylase; IHC = immunohistochemistry.
- Figure 2 Patients treated with immunotherapy
Disease courses and treatment regimens of the 27 patients that were treated with immunotherapy. In patients with overlapping syndromes, the specific syndromes are indicated below the gy bar with the corresponding color at the relative time when they were diagnosed. Symbols inside the color bars show specific treatments or the moment they were initiated. A line with the same color is used for chronic (continuous line) and periodic (discontinuous line) treatments to show their duration. Symbols on the left side correspond to those in Figure 5.
- Figure 3 Antibody concentrations and clinical syndromes
Patients were grouped according to their clinical phenotype into 1 of the 4 classical anti–GAD65-associated syndrome categories, in the overlap or other category. Serum (A) and CSF (B) ELISA concentrations are shown in a logarithmic scale. Small black dots represent patients with low antibody concentrations. The specific symptoms of these patients are listed in the supplementary material. Orange dots in the SPS column were patients with progressive encephalomyelitis with rigidity and myoclonus, which is considered an extended form of SPS. (C) Serum/CSF ratio of anti-GAD65 ELISA values within the different syndromes in the high-concentration group. The blue ribbon represents the ratio-frame where intrathecal antibody synthesis would be expected to start. CA = cerebellar ataxia; Ep = epilepsy; GAD = glutamic acid decarboxylase; LE = limbic encephalitis; SPS = stiff-person syndrome.
- Figure 4 Disease course and treatment response of 4 patients in the high-concentration group
Horizontal bars containing treatment abbreviations represent the time periods of the corresponding treatments. Blue vertical lines represent seizure frequency over time. Green discontinuous line connected by green circles shows evolution of serum anti-GAD65 concentration. Thick dark-blue line connected by rhomboids represents functional status over time, according to the visual score at the right most part of the charts. AED = antiepileptic drug; AZA = azathioprine; GAD = glutamic acid decarboxylase; IVIg = IV immunoglobulin; IVMP = IV methylprednisolone; MMF = mycophenolate mofetil; PDN = prednisone; RTX rituximab.
- Figure 5 Antibody concentration response to immunotherapy
Concentration responses to treatment of the 17 patients of whom pretreatment and posttreatment samples were available. Red lines represent the patients lacking clinical improvement. The blue dashed line in the right graph represent CSF samples obtained pretreatment and at clinical relapse. A reduction of at least 25% following immunotherapy was considered a relevant concentration reduction. GAD = glutamic acid decarboxylase.
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