Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. Approximately 30–40% of patients treated with neurotoxic chemotherapy will develop CIPN and there is considerable variability in its severity between patients. It is often sensory-predominant with pain and can lead to long-term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents.

ObjectiveTo determine the proportion of true and false positives from paraneoplastic panels and effects on downstream testing/treatment.MethodsUsing a retrospective cohort study design, we identified 500 consecutive patients with Mayo paraneoplastic autoantibody testing and performed chart abstraction. Paraneoplastic presentation types were categorized into probable, possible, and other by consensus. True positives were defined as a positive antibody titer with no other explanation found in addition to one of the following: syndrome known to be associated with the antibody, clinical improvement with treatment, and new malignancy. Comparisons of diagnostic testing and treatments between false and true positives were performed. Multivariable logistic regression was used to evaluate associations between patient-level factors and true positives.ResultsThe mean (SD) age of the population was 55.4 (17.1) years, and 55.4% were female, with 1.3 (1.2) years of follow-up. Of the 500 tests, 87 (17.4%, 95% confidence interval [CI] 14.1%–20.7%) were positive and 62 (71.3%, 95% CI 61.8%–80.8%) of these were false positives. Of those with a possible/other presentation (n = 369), 2 (0.5%, 95% CI 0.0%–1.0%) were true positives. CT of the chest (30.7% vs 11.8%, p ≤ 0.01) was performed more often in false positives than true negatives. Probable presentation type (odds ratio [OR] 57.9, 95% CI 12.5–268.0) and outpatient setting (OR 8.7, 95% CI 2.4–31.8) were associated with true-positive results.ConclusionParaneoplastic tests result in a large proportion of false positives, particularly in those with clinical presentations that are not well established as paraneoplastic diseases. Future work should construct panels targeted to specific clinical presentations and ensure that tests are ordered in the appropriate clinical context.

Glioblastoma might have widespread effects on the neural organization and cognitive function, and even focal lesions may be associated with distributed functional alterations. However, functional changes do not necessarily follow obvious anatomical patterns and the current understanding of this interrelation is limited. In this study, we used resting-state functional magnetic resonance imaging to evaluate changes in global functional connectivity patterns in 15 patients with glioblastoma. For six patients we followed longitudinal trajectories of their functional connectome and structural tumour evolution using bi-monthly follow-up scans throughout treatment and disease progression. In all patients, unilateral tumour lesions were associated with inter-hemispherically symmetric network alterations, and functional proximity of tumour location was stronger linked to distributed network deterioration than anatomical distance. In the longitudinal subcohort of six patients, we observed patterns of network alterations with initial transient deterioration followed by recovery at first follow-up, and local network deterioration to precede structural tumour recurrence by two months. In summary, the impact of focal glioblastoma lesions on the functional connectome is global and linked to functional proximity rather than anatomical distance to tumour regions. Our findings further suggest a relevance for functional network trajectories as a possible means supporting early detection of tumour recurrence.

Purpose of this review Diabetic peripheral neuropathy (DPN) is a disabling, highly prevalent complication of both type 1 and type 2 diabetes mellitus (T1DM, T2DM). Large clinical studies support the concept that, in addition to hyperglycemia, components of the metabolic syndrome (MetS) may underlie the pathogenesis of DPN, especially in T2DM. This review will present the evidence supporting the MetS and its individual components as potential causal factors for the development of neuropathy. Recent findings In addition to poor glycemic control and duration of diabetes, components of MetS such as dyslipidemia, obesity, and hypertension, may have an important impact on the prevalence of DPN. Obesity and prediabetes have the most data to support their role in neuropathy, whereas hypertension and dyslipidemia have more mixed results. Non-metabolic factors, such as genetic susceptibility, age, height, gender, smoking, and alcohol, have also been highlighted as potential risk factors in peripheral neuropathy, although the exact contribution of these factors to DPN remains unknown. Summary DPN is a chronic and disabling disease, and the accurate identification and modification of DPN risk factors is important for clinical management. Recent data support a role for components of the MetS and other risk factors in the development of DPN, offering novel targets beyond hyperglycemia for therapeutic development.