PMC8489187_01
Bone scintigraphy with 99mTc-MDP in May 2016 showing abnormal bone uptake in 5th, 6th and 7th right coastal arches (arrow).
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The uptake in fifth and seventh ribs observed in 99mTC-MDP SC (Figure 1) was not confirmed in 99mTC-MIBI SC (Figure 2).
Normal bone uptake with slight uptake in the myocardium (arrow) at bone scintigraphy with 99mTc-MIBI in November 2016.
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The uptake in fifth and seventh ribs observed in 99mTC-MDP SC (Figure 1) was not confirmed in 99mTC-MIBI SC (Figure 2).
Normal bone uptake with 99mTc-MDP in October 2017, showing distension of urinary tract (arrows).
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Due to the marked motor worsening (NIS 88.5, ONLS 3 UL and 5 LL) and the onset of pain and other autonomic complaints (orthostatic intolerance and voiding dysfunction), Fludarabine (100 mg/iv/monthly) was prescribed from December 2016 to April 2017, resulting in slight improvement (NIS 83.5, ONLS 3 UL and 4 LL) and disappearance of bone uptake in coastal arches but showing distension of urinary tract (Figure 3).
Optic microscopy of sural nerve biopsy. A - Extracellular eosinophilic deposits in the endoneuro (arrows) (H&E, X200); B - Semithin section (araldite-embedded) showing nerve fascicles with severe loss of thick and thin myelinated fibers and large amyloid deposits in the endoneuro (asterisk) and around endoneural blood vessels (arrows) (Toluidine blue, X200); C - Congo red staining showing deposits in the endoneuro (arrows) and epineuro (arrowhead) (X100) showing endoneural apple-green birefringence under polarized light in D (X200).
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A sural nerve biopsy (February 2018) revealed amyloid deposition (Figures 4) with IgA positivity and non-specific lambda light-chain staining by immunohistochemistry (IHC) (Figures 5A-C).
Brown immunolabeling with anti-IgA antibody (A) showing two large positive areas in the endoneuro (asterisk) and around an epineural blood vessel (arrow). Intense non-specific background immunolabeling was seen with anti-lambda (B) and anti-kappa (C) light-chains antibodies [Horseradish peroxidase, X200]. D - Brown immunolabeling with anti-Transthyretin antibody showing large positive amyloid deposits in the epineuro at the same endoneural area showed in 5A (asterisk) [Horseradish peroxidase, X100].
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Only in 2019 was it possible to carry out an IHC staining for TTR in the stored nerve tissue biopsy, which showed positive staining at the same sites of previous IgA deposition (Figure 5D).
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Brown immunolabeling with anti-IgA antibody (A) showing two large positive areas in the endoneuro (asterisk) and around an epineural blood vessel (arrow). Intense non-specific background immunolabeling was seen with anti-lambda (B) and anti-kappa (C) light-chains antibodies [Horseradish peroxidase, X200]. D - Brown immunolabeling with anti-Transthyretin antibody showing large positive amyloid deposits in the epineuro at the same endoneural area showed in 5A (asterisk) [Horseradish peroxidase, X100].
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Only in 2019 was it possible to carry out an IHC staining for TTR in the stored nerve tissue biopsy, which showed positive staining at the same sites of previous IgA deposition (Figure 5D).
Strong diffuse uptake in ventricular walls at 99mTc-pyrophosphate scintigraphy in May 2019.
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Tc99m-pyrophosphate SC showed strong diffuse uptake in ventricular walls in February 2019 (Figure 6), with heart/contralateral area ratio of 1.9 and 1.7 after 1 and 3 hours, respectively, highly suggestive of
Mass spectrometry data of the sural nerve. After selecting the amyloid deposit area, tissue microdissection and laser capture, the analysis of the peptide fragments revealed the presence of three proteins: transthyretin as the amyloidogenic protein and two other constituents common to all types of amyloidosis, apolipoprotein E and serum amyloid P-component. The protein recognition occurs when 3 or more peptide fragments of a specific protein are identified in the sample [spectra acquired by Q-Exactive HF-X spectrometer and analised using MaxQuant, version 1.6.15.0].
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