Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain-Barré syndrome: a case report.

Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain-Barré syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain-Barré syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain-Barré syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab.

GDF-15, a mitochondrial disease biomarker, is associated with the severity of multiple sclerosis.

GDF-15, a member of the transforming growth factor beta superfamily, regulates inflammatory and apoptotic pathways in various diseases, such as heart failure, kidney dysfunction, and cancer. We aimed to clarify potentially confounding variables affecting GDF-15 and demonstrate its utility as a mitochondrial biomarker using serum samples from 15 patients with mitochondrial diseases (MD), 15 patients with limbic encephalitis (LE), 10 patients with multiple sclerosis/neuromyelitis optica spectrum disorders (MS/NMOSD), and 19 patients with amyotrophic lateral sclerosis (ALS). GDF-15 and FGF-21 were significantly elevated in MD. GDF-15 and FGF-21 showed a good correlation in MD but not in LE, MS, and ALS. GDF-15 was potentially influenced by age in LE, MS/NMOSD, and ALS but not in MD. FGF-21 was not correlated with age in MS/NMOSD, ALS, LE, and MD. GDF-15 was not correlated with clinical features in LE or BMI or body weight in ALS. GDF-15 positively correlated with the Expanded Disability Status Scale (EDSS) in MS/NMOSD, while EDSS showed no correlation with age. In conclusion, the results revealed that GDF-15 may be influenced by EDSS in MS/NMOPSD and by age in LE, MS/NMOSD, and ALS but not in MD. Mitochondrial damage in MS/NMOSD is a potentially confounding variable affecting GDF-15.

Acetylcholinesterase inhibitor treatment alleviated cognitive impairment caused by delayed encephalopathy due to carbon monoxide poisoning: Two case reports and a review of the literature.

INTRODUCTION: Delayed encephalopathy due to carbon monoxide (CO) poisoning can even occur in patients with mild symptoms of acute CO poisoning. Some cases taking conventional hyperbaric oxygen (HBO) therapy or steroid-pulse therapy may be insufficient, and AchEI may be effective. PATIENT CONCERNS AND DIAGNOSES: We report two cases of delayed encephalopathy after acute CO poisoning involving two women aged 69 (Case 1) and 60 years (Case 2) whose cognitive function improved with acetylcholinesterase inhibitor (AchEI) treatment. Delayed encephalopathy occurred 25 and 35 days after acute CO poisoning in Case 1 and Case 2, respectively. Both patients demonstrated cognitive impairment, apathy, and hypokinesia on admission. INTERVENTIONS AND OUTCOMES: Although hyperbaric oxygen therapy did not yield any significant improvements, cognitive dysfunction improved substantially. This was evidenced by an improved Mini-Mental State Examination score ffom 9 to 28 points in Case 1 and an improved Hasegawa's dementia rating scale score from 4 to 25 points in Case 2 after administration of an AchEI. In Case 1, we administered galantamine hydrobromide, which was related with improved white matter lesions initially detected on brain magnetic resonance imaging. However, in Case 2 white matter lesions persisted despite AchEI treatment. AchEI treatment may result in improved cognitive and frontal lobe function by increasing low acetylcholine concentrations in the hippocampus and frontal lobe caused by decreased nicotinic acetylcholine receptor levels in delayed encephalopathy after CO poisoning. CONCLUSION: Physicians should consider AchEIs for patients demonstrating delayed encephalopathy due to CO poisoning.

Medial medullary infarction caused by antineutrophil cytoplasmic antibody-related vasculitis: Case report and review of the literature.

RATIONALE: Medial medullary infarction accounts for less than 1% of brain infarctions, and medial medullary infarctions is very rarely caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. PATIENT CONCERNS: We report the case of a 76-year-old man at low risk of arteriosclerosis who presented with disorders on the left side including gaze-evoked nystagmus, paralysis of the extremities, pyramidal signs, sensory disturbance, and dysesthesia. Brain magnetic resonance imaging also showed right medial medullary infarction. DIAGNOSES: Medial medullary infarction caused by ANCA-related vasculitis was diagnosed based on mild renal dysfunction and high levels of blood leukocytes, C-reactive protein (CRP), and myeloperoxidase (MPO)-ANCA. INTERVENTIONS AND OUTCOMES: He underwent two 3-day courses of steroid pulse therapy involving daily 1000 mg doses of methylpredonine. He then received 30 mg/day (0.5 mg/kg/day) of prednisolone (PSL) without other immunosuppressants. Levels of MPO-ANCA and the inflammatory marker CRP decreased rapidly a month after admission. Once MPO-ANCA became undetectable, the PSL dose was carefully reduced to 10 mg/day. To treat his paralysis, we provided rehabilitation with a Hybrid Assistive Limb five times starting at a month post-onset. His Barthel index score rose from 45 to 70 points. LESSONS: Medullary infarction is mostly caused by arteriosclerosis and vertebral arterial dissection. When systemic inflammatory findings are obtained, ANCA-associated vasculitis should be considered a potential cause, and steroid pulse therapy should be promptly administered.

Vestibular Impairment in Frontotemporal Dementia Syndrome.

BACKGROUND: No studies to date have attempted to evaluate frontotemporal lobar degeneration from the perspective of the vestibular system. OBJECTIVE: The present study examined vestibular function in patients with frontotemporal dementia (FTD) clinical syndrome and evaluated whether vestibular disorders are involved in the clinical symptoms due to FTD. METHODS: Fourteen patients with FTD syndrome, as well as healthy elderly controls without dementia, were included in the present study. All subjects underwent vestibular function tests using electronystagmography, such as caloric tests and visual suppression (VS) tests, in which the induced caloric nystagmus was suppressed by visual stimuli. The association between clinical symptoms and vestibular function in the FTD syndrome group was further examined. RESULTS: In the FTD syndrome group, caloric nystagmus was not necessarily suppressed during VS tests. Furthermore, VS was observed to be significantly impaired in FTD syndrome patients with gait disturbance as compared to those without such disturbance. CONCLUSION: The present study revealed that impairment of VS in patients with FTD results in an inability to regulate vestibular function by means of visual perception, regardless of multiple presumed neuropathological backgrounds. This could also be associated with gait disturbance in patients with FTD syndrome.