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

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

ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function

Derlin family members (Derlins) are primarily known as components of the endoplasmic reticulum-associated degradation pathway that eliminates misfolded proteins. Here we report a function of Derlins in the brain development. Deletion of Derlin-1 or Derlin-2 in the central nervous system of mice impaired postnatal brain development, particularly of the cerebellum and striatum, and induced motor control deficits. Derlin-1 or Derlin-2 deficiency reduced neurite outgrowth in vitro and in vivo and surprisingly also inhibited sterol regulatory element binding protein 2 (SREBP-2)-mediated brain cholesterol biosynthesis. In addition, reduced neurite outgrowth due to Derlin-1 deficiency was rescued by SREBP-2 pathway activation. Overall, our findings demonstrate that Derlins sustain brain cholesterol biosynthesis, which is essential for appropriate postnatal brain development and function

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

Severe Orthostatic Hypotension due to Unilateral Carotid Artery Dissection

A 46-year-old woman was admitted to our hospital with mild right-sided hemiparesis and orthostatic hypotension. Magnetic resonance angiography of the neck showed stenosis of the left distal carotid sinus surrounded by intraluminal hyperintensities on both T1-weighted and T2-weighted images, representing a periluminal hematoma secondary to carotid artery dissection. The dissection hyperextended the carotid artery wall and stimulated baroreceptors in the carotid sinus. The stimulated baroreceptors induced carotid sinus hypersensitivity, which may have been related to her orthostatic hypotension. Post-stroke orthostatic hypotension should prompt consideration of carotid artery dissection

Optic Neuropathy with Features Suggestive of Optic Neuritis in Cerebrotendinous Xanthomatosis

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