A Case of Nivolumab-Induced Severe Mononeuropathy Multiplex and Rhabdomyolysis

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

Identification of a single base insertion in the COL4A5 gene in Alport syndrome

Identification of a single base insertion in the COL4A5 gene in Alport syndrome. We identified a novel mutation in the COL4A5 gene of a Japanese patient with Alport syndrome. A combination of in vitro amplification of the exons with single strand conformation polymorphisms (SSCP) analysis suggested the presence of a mutation in exon 48. Sequencing of the amplified DNA revealed a single base (T) insertion which was between nucleotides T 4750 and G 4751 within the methionine 1516. This mutation caused a shift in the reading frame of nine amino acids and introduced a premature termination signal that would be expected to lack about two-thirds of the noncollagenous (NCI) domain. This mutation may interfere with type IV collagen assembly leading to increased permeability and play a causative role in the glomerular basement membrane abnormality of this patient with typical Alport syndrome. Gene tracking by restriction enzyme NlaIII digestion revealed that the patient's mother is heterozygous whereas the patient's brother and one sister are normal, albeit they have hematuria and proteinuria. Without gene analysis, they would have been misdiagnosed. We propose that the diagnosis of Alport syndrome should be made on the basis of both clinical phenotypes and molecular defects

Three Pediatric Patients with Congenital Nephrogenic Diabetes Insipidus due to AVPR2 Nonsense Mutations and Different Clinical Manifestations: A Case Report

Congenital nephrogenic diabetes insipidus (CNDI), a rare hereditary disorder, is characterized by the inability of the kidneys to concentrate urine in response to the antidiuretic hormone arginine vasopressin (AVP); as a result, large volumes of unconcentrated urine are excreted. In addition to the clinical manifestations of CNDI, such as dehydration and electrolyte disturbances (hypernatremia and hyperchloremia), developmental delay can result without prompt treatment. In approximately 90% of cases, CNDI is an X-linked disease caused by mutations in the arginine vasopressin receptor 2 (AVPR2) gene. In approximately 9% of cases, CNDI is an autosomal recessive disease caused by mutations in the water channel protein aquaporin 2 (AQP2), and 1% of cases are autosomal dominant. We report a case of CNDI caused by a novel AVPR2 nonsense mutation, c.520C>T (p.Q174X), and cases of siblings in another family who had a different AVPR2 nonsense mutation, c.852G>A (p.W284X). Both cases responded well to treatment with hydrochlorothiazide and spironolactone. If CNDI is suspected, especially in carriers and neonates, aggressive genetic testing and early treatment may alleviate growth disorders and prevent irreversible central nervous system disorders and developmental delay

A case of acute myocardial infarction during perioperative period of non-cardiac surgery in a patient with antiphospholipid syndrome and a history of coronary artery bypass surgery

AbstractA 65-year-old woman underwent coronary artery bypass surgery and was diagnosed with antiphospholipid syndrome (APS) at the same time in 1985. She was admitted to our hospital to undergo mastectomy for left breast cancer in 2012. She was put on intravenous infusion of heparin and stopped receiving both antiplatelet agents and warfarin. The operation was performed without complications, and antithrombotic therapy was restarted one day after the operation. On day 6 postoperative, she complained of sudden chest pain and on examination she was diagnosed with acute myocardial infarction. The culprit lesion was in a saphenous vein graft and coronary intervention was performed.<Learning objective: Antithrombotic therapy for patients with APS is complicated because of prolonged baseline activated partial thromboplastin time (aPTT). An effective perioperative antithrombotic therapy for APS patients who have a history of coronary artery disease and have undergone non-cardiac surgery has not yet been established. A safe strategy for such a therapy should therefore be discussed.

18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging evaluation of chorea

Chorea is thought to be caused by deactivation of the indirect pathway in the basal ganglia circuit. However, few imaging studies have evaluated the basal ganglia circuit in actual patients with chorea. We investigated the lesions and mechanisms underlying chorea using brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This retrospective case series included three patients with chorea caused by different diseases: hyperglycemic chorea, Huntington’s disease, and subarachnoid hemorrhage. All the patients showed dysfunction in the striatum detected by both MRI and FDG-PET. These neuroimaging findings confirm the theory that chorea is related to an impairment of the indirect pathway of basal ganglia circuit

In situ evaluation of podocin in normal and glomerular diseases

In situ evaluation of podocin in normal and glomerular diseases.BackgroundMutations of the NPHS2 gene are responsible for autosomal-recessive steroid-resistant nephrotic syndrome. Its product, podocin, faces the slit diaphragm area with its two ends in the cytoplasm of foot processes.MethodsWe generated rabbit polyclonal antibodies against conjugated peptides from human podocin N- and C-termini, and studied podocin and synaptopodin using kidney tissues of normal humans and those with glomerular diseases.ResultsAntipodocin antibodies detected the original 42 kD fragment and an extra smaller fragment by Western blot analysis using human isolated mature glomeruli. RNA analysis showed two bands, the original and the other of a decreased length. Immunohistochemically, podocin was detected in a linear pattern along the glomerular capillary loop. Antipodocin antibody (C-terminal) stained the smooth muscles of renal arterioles and aorta. Among 42 patients, podocin was normally expressed in glomeruli in purpura nephritis, IgA nephropathy (IgAN), and minimal-change disease (MCD), while it was either decreased or absent in most subjects with focal segmental glomerulosclerosis (FSGS). The expression of synaptopodin was similar to that of podocin, although some discrepancy existed.ConclusionAlthough indirect, our data suggest the existence of a vascular isoform of podocin with a different molecular mass. We propose that examination of podocin expression may help differentiate MCD from FSGS

Preparation of Ultrafine Fe–Pt Alloy and Au Nanoparticle Colloids by KrF Excimer Laser Solution Photolysis

We prepared ultrafine Fe–Pt alloy nanoparticle colloids by UV laser solution photolysis (KrF excimer laser of 248 nm wavelength) using precursors of methanol solutions into which iron and platinum complexes were dissolved together with PVP dispersant to prevent aggregations. From TEM observations, the Fe–Pt nanoparticles were found to be composed of disordered FCC A1 phase with average diameters of 0.5–3 nm regardless of the preparation conditions. Higher iron compositions of nanoparticles require irradiations of higher laser pulse energies typically more than 350 mJ, which is considered to be due to the difficulty in dissociation of Fe(III) acetylacetonate compared with Pt(II) acetylacetonate. Au colloid preparation by the same method was also attempted, resulting in Au nanoparticle colloids with over 10 times larger diameters than the Fe–Pt nanoparticles and UV–visible absorption peaks around 530 nm that originate from the surface plasmon resonance. Differences between the Fe–Pt and Au nanoparticles prepared by the KrF excimer laser solution photolysis are also discussed

Clinical features and electrocardiogram parameters in Parkinson’s disease

We investigated the relation between clinical features and electrocardiogram (ECG) parameters in patients with Parkinson’s disease (PD). One hundred and fifty-six PD patients were enrolled. Their clinical features [body mass index (BMI), age, disease duration, and disease stage] and ECG parameters [RR, PR, QRS, and QT intervals, and heart rate-corrected QT (QTc)] were analyzed. BMI was positively correlated with the PR and QRS intervals in patients with PD. The QRS interval was positively correlated with disease duration and Hoehn and Yahr stage, and the QT interval and QTc were positively correlated with age. Clinical features and ECG parameters are likely to be closely associated with each other. Several ECG parameters reflect autonomic dysfunction or disease progression. Clinicians should pay more attention to ECG parameters in the treatment of PD patients

Body Mass Index and Severity of Parkinsonism in Multiple System Atrophy

Patients with neurodegenerative disorders lose body weight as their diseases progress. In Parkinson’s disease (PD), however, autonomic dysfunction is associated with increased body mass index (BMI). We investigated the correlation between BMI, clinical features, and autonomic dysfunction in patients with multiple system atrophy with predominant parkinsonism (MSAP). BMI, clinical features, cardiac 123Imetaiodobenzylguanidine scintigraphy (MIBG), Hoehn and Yahr (H-Y) stage, and the coefficient of variation of the R-R interval (CVRR) were analyzed in 50 patients with MSA-P. BMI showed no significant correlation with MIBG parameters or CVRR. On the other hand, the H-Y stage was significantly negatively correlated with BMI. Higher H-Y stage indicates a more severe neuromuscular state in MSA-P and is considered to be related to higher energy expenditure and decrease of BMI. Patients with MSA-P lose weight as the disease progresses. This is the first report indicating a significant correlation between disease severity and BMI decrease in MSA