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Additional file 2: Figure S2. Sequence reads were visualized by Ion Reporter Genome Viewer. Representative images of read alignments (BAM files) of sample #2 were visualized with Ion Reporter Genome Viewer. There are no mutated reads corresponding to NRAS p.G12C (c.34G > T: chr1:115,258,748) in the next generation sequencing data.

We describe our encounter with a 39-year-old man who exhibited acute painless visual loss and progressive gait disturbance. He had tendinous xanthoma and several neuroophthalmological findings indicative of optic neuropathy in the right eye, including afferent pupillary defect, cecocentral scotoma, and optic disc swelling. Neurological examination showed cerebellar ataxia and pyramidal weakness. Brain magnetic resonance imaging revealed bilateral swelling in the optic nerves with gadolinium-enhancement suggesting optic neuritis, an enlarged fourth ventricle, atrophy of the cerebellum, and hyperintensities in the bilateral dentate nuclei. The patient was diagnosed with cerebrotendinous xanthomatosis (CTX) based on an elevated serum cholestanol level and a homozygous missense mutation in CYP27A1. CTX is a genetic lipid storage disease caused by dysfunction of the mitochondrial enzyme sterol 27-hydroxylase. With respect to ophthalmological manifestations, juvenile cataracts and optic neuropathy are common findings in patients with CTX, but there have been no reports of optic neuropathy with features suggestive of optic neuritis. Thus, this case illustrates that clinicians should consider a diagnosis of CTX in patients with cardinal features of CTX even if the patients show signs indicative of optic neuritis.

Additional file 1: Figure S1. Principle of BNA-clamp PCR. Forward and reverse primers amplify the targeted mutation. A BNA probe binds to the wild-type allele but not to the mutated allele. The BNA probe selectively inhibits PCR amplification of the wild-type allele. F, fluorescence; Q, quencher.

Additional file 3: Figure S3. Amplification plot of dilution experiment by BNA-clamp PCR method. Wild-type control DNA was spiked in the Tru-Q 7 (1.3% Tier) Reference Standard. BNA-clamp PCR was performed using serial dilution DNA. (A) DNA containing KRAS mutation at codon 12/13 (dilution range: 1–33% variant allele fraction) and (B) BRAF mutation at codon 600 (dilution range: 0.4–12% variant allele fraction).

We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL) was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL) was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days) followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs). However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately.