PMC10331165_01
Native axial FLAIR MR-images of the patient 4 months after symptom onset (A) and after clinical deterioration 5 months after treatment with rituximab (B). No cerebellar atrophy or inflammatory lesions were detected. The clinical course of the patient at different time-points with corresponding treatment regimens, SARA-score values, and antibody titer ratio in both CSF and serum is depicted (C). CS, corticosteroids; RTX, rituximab; PLEX, plasma exchange; BTZ, bortezomib.
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F1
Magnetic resonance imaging (MRI) of the brain and spinal cord showed no abnormalities (Figure 1A). The patient was initially treated with intravenous methylprednisolone over 5 days (1 g per day), followed by oral tapering starting with 80 mg prednisone per day, but this treatment did not produce any significant clinical effect (Figure 1C). Her SARA score had increased to 22, and we also found increased anti-septin IgG titer in serum (1:100), while MRI still showed no signs of inflammation or degeneration (Figure 1B).
(A, B) Strong neuropil staining of rat hippocampus (A left, B left; scale bar: 200 mum) and primate cerebellum (A right, B right; scale bar: 100 mum) after incubation with patient CSF (A) and serum (B), both from the time of diagnosis. The inner molecular layer ( ) of the hippocampus exhibits a weaker immune-reactivity, compared to the outer layer (+). The molecular layer of the cerebellum (*) exhibits a stronger immune-reactivity as compared to the granular layer (#). (C) Cell-based assay with human Septin-5 transfected HEK-293 T cells confirms the presence of antibodies against Septin-5 in both patient CSF and serum (dilutions: Serum 1:100, CSF 1:10; scale bar: 100 mum). (D) Negative controls of rat hippocampus (left) and primate cerebellum (right). Weak immune-reactivity is due to secondary antibodies within the vessels. Green: Alexa-488 Anti-human IgG, blue: DAPI. CSF, cerebrospinal fluid; HC, healthy control.
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F2
Table 1), revealed serum (1:10.000; reference value: < 1:100) and CSF (1:320; reference-value: negative) anti-septin-5 IgG (Figure 2); no other auto-antibodies were detected. Tests for thyroid function and antibodies, including TSH (Thyroid-Stimulating Hormone), T3 (Triiodothyronine), T4 (thyroxine), auto-antibodies against TPO (Thyroid peroxidase), thyroglobulin and TSH-receptor, were normal.