Cerebrospinal Fluid Interleukin-6 in Immune Checkpoint Inhibitor-Induced Autoimmune Meningoencephalitis.

Immune checkpoint inhibitors (ICIs) have proven clinical benefits in various advanced cancers. However, despite their significant therapeutic efficacy, ICIs induce immune-related adverse events. Among these events, autoimmune meningoencephalitis often has severe effects on patients' outcomes, but its specific clinical features are still unclear. Here, we report two cases of ICI-associated meningoencephalitis with elevated interleukin-6 (IL-6) levels in the cerebrospinal fluid (CSF). A 47-year-old woman (Case 1) with renal cell carcinoma developed severe headache after a seventh nivolumab administration. A neurological examination revealed jolt accentuation signs and hyperreflexia in all extremities. CSF analysis revealed a high IL-6 value (6,620 pg/mL) with marked pleocytosis. A 70-year-old woman (Case 2) who received an initial administration of nivolumab plus ipilimumab for renal cell carcinoma developed alterations of consciousness. She presented with impaired consciousness, neck stiffness, and hyperreflexia in all extremities. CSF analysis demonstrated a high IL-6 value (49.3 pg/mL) with mild pleocytosis. Both patients were treated with steroid pulse therapy (methylprednisolone 1,000 mg/day, 3 days), followed by the administration of oral predonisolone. The symptoms and laboratory findings improved in both cases. CSF IL-6 values were proportional to the severity of meningoencephalitis and other clinical parameters. These findings may help elucidate the mechanisms of central nervous system complications that are caused by ICIs.

[Intravenous immunoglobulin in combination with ibrutinib for the treatment of IgM-type M protein associated peripheral neuropathy complicated with chronic lymphocytic leukemia].

We report the case of a 79-year-old man with chronic lymphocytic leukemia (CLL) with IgM-kappa type monoclonal gammopathy according to immunophenotypes and a negative result for MYD88 L265P mutation of leukemic cells. Abnormal lymphocytes and IgM increased under observation, and he experienced paresthesia. The diagnosis of IgM-type M protein associated peripheral neuropathy was confirmed by nerve conduction test, and negativity of myelin-associated glycoprotein and glycolipid antibodies. He was placed on intravenous immunoglobulin (IVIg) in combination with ibrutinib. His symptoms dramatically subsided and did not recur. Treatment with IVIg and ibrutinib may be useful for the rare complication of peripheral neuropathy with CLL.

Association of Cerebrospinal Fluid Adiponectin Levels With Cerebral Glucose Metabolism In Mild Cognitive Impairment: A Pilot Study.

BACKGROUND: Adiponectin has been implicated in the pathophysiology of dementia, especially Alzheimer's disease. However, the association between cerebrospinal fluid (CSF) adiponectin levels and positron emission tomography (PET) imaging remains unclear. OBJECTIVE: To explore whether CSF adiponectin levels are associated with 11C-Pittsburgh compound B (PiB) or 18F-fluorodeoxyglucose (FDG) uptake in amnestic mild cognitive impairment (MCI) subjects. METHODS: Thirty-four amnestic MCI subjects underwent PiB-PET, FDG-PET, and CSF analysis. The CSF adiponectin levels were measured using the Bio-Plex 200 suspension array system. PET uptake was assessed for the frontal and temporoparietal lobes and posterior cingulate gyrus, referenced against the cerebellar cortex. The increased brain amyloid burden was defined as a mean uptake value ratio greater than 1.4. Spearman's rank correlation analysis and a multiple regression model were used to examine the association between CSF adiponectin levels and PiB or FDG uptake. RESULTS: The mean age was 76.3 years; 38.2% were men, and 61.8% were women. A high amyloid burden was identified in 18 (52.9%) subjects. CSF adiponectin levels positively correlated with global FDG uptake (ß = 0.45; 95% confidence interval (CI), 0.13 to 0.76, p < 0.01), especially in the parietotemporal lobe and posterior cingulate gyrus (ß = 0.70; 95% CI, 0.41 to 0.99, p<0.01, ß = 0.33; 95% CI, 0.03 to 0.63, p = 0.03, respectively) after adjusting for covariates, including age, sex, education years, body mass index, vascular risk factors, ApoEε4 status, and PiB status in all amnestic MCI subjects. CONCLUSION: CSF adiponectin levels were associated with cortical glucose metabolism, particularly in the specific regions that connect with the medial temporal, but not brain amyloid burden in amnestic MCI subjects.

Relationship between cytokine levels in the cerebrospinal fluid and 11C-Pittsburgh compound B retention in patients with mild cognitive impairment.

AIM: In the present study, we examined the relationship between cytokine levels in the cerebrospinal fluid (CSF) and 11 C-Pittsburgh compound B (PiB) retention in patients with mild cognitive impairment. METHODS: A total of 33 participants (12 men and 21 women; mean age 76.5 years) with mild cognitive impairment underwent neuropsychological assessments, PiB positron emission tomography and analysis of cytokine levels in the CSF. The CSF levels of 48 cytokines and growth factors were measured using multiplex immunoassays. PiB retention was assessed based on a standardized uptake value ratio. Mild cognitive impairment participants were classified as PiB-positive and PiB-negative, with a cut-off level of 1.4. We compared the CSF cytokine levels and Alzheimer's disease biomarkers, including ß-amyloid 1-42, total tau and tau phosphorylated at threonine 181, between the two subgroups, and evaluated the correlation between PiB retention or CSF Alzheimer's disease biomarkers and CSF cytokine levels. RESULTS: Cytokine levels in the CSF did not differ between the two subgroups. Macrophage inflammatory protein-1ß levels in the CSF significantly correlated with PiB retention only in the PiB-positive subgroup, whereas stem cell growth factor-ß levels significantly correlated with PiB retention in the PiB-negative subgroup. Furthermore, stem cell growth factor-ß levels significantly correlated with total tau and tau phosphorylated at threonine 181 levels in only the PiB-negative subgroup. CONCLUSION: The present findings suggest that macrophage inflammatory protein-1ß and stem cell growth factor-ß are associated with chronic inflammatory processes accompanied by amyloid deposition or AD pathophysiology. Geriatr Gerontol Int 2017; 17: 1907-1913.