Melanin-Concentrating Hormone Is Associated With Delayed Neurocognitive Recovery in Older Adult Patients With Preoperative Sleep Disorders Undergoing Spinal Anesthesia.

BACKGROUND: Aging and preoperative sleep disorders are the main risk factors affecting postoperative cognitive outcomes. However, the pathogenesis of delayed neurocognitive recovery after surgery remains ambiguous, and there is still a lack of potential biomarkers for delayed neurocognitive recovery in older adult patients with preoperative sleep disorders. Our study aimed to explore the relationship between melanin-concentrating hormone (MCH) and delayed neurocognitive recovery early after surgery in older adult patients with preoperative sleep disorders. METHODS: In this monocentric prospective observational study, 156 older adult patients (aged 65 years or older) with preoperative sleep disorders undergoing elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) were included at an academic medical center in Inner Mongolia, China, from October 2021 to November 2022, and all patients underwent spinal anesthesia. The Pittsburgh Sleep Quality Index (PSQI) was applied to assess the preoperative sleep quality of all patients, and preoperative sleep disorders were defined as a score of PSQI >5. We measured the levels of cerebrospinal fluid (CSF) MCH and plasma MCH of all patients. The primary outcome was delayed neurocognitive recovery early after surgery. All patients received cognitive function assessment through the Montreal Cognitive Assessment (MoCA) 1 day before and 7 days after surgery (postoperative day 7 [POD7]). Delayed neurocognitive recovery was defined as a score of POD7 MoCA <26. The potential confounders included variables with P < .2 in the univariate logistic analysis, as well as the important risk factors of delayed neurocognitive recovery reported in the literature. Multivariable logistic regression model based on the Enter method assessed the association of MCH and delayed neurocognitive recovery in older adult patients with preoperative sleep disorders. RESULTS: Fifty-nine (37.8%) older adult patients with preoperative sleep disorders experienced delayed neurocognitive recovery at POD7. Increase in CSF MCH levels (odds ratio [OR] for an increase of 1 pg/mL = 1.16, 95% confidence interval [CI], 1.09-1.23, P < .001) and decrease in plasma MCH levels (OR for an increase of 1 pg/mL = 0.92, 95% CI, 0.86-0.98, P = .003) were associated with delayed neurocognitive recovery, after adjusting for age, sex, education, baseline MoCA scores, American Society of Anesthesiologists (ASA) grade, and coronary heart disease (CHD). CONCLUSIONS: In older adult patients with preoperative sleep disorders, MCH is associated with the occurrence of delayed neurocognitive recovery after surgery. Preoperative testing of CSF MCH or plasma MCH may increase the likelihood of identifying the high-risk population for delayed neurocognitive recovery in older adult patients with preoperative sleep disorders.

Cerebrospinal fluid melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) in Alzheimer's disease.

Ancillary to decline in cognitive abilities, patients with Alzheimer's disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62) = 8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r = 0.47; p<0.01) and P-tau (r = 0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = -0.362, p<0.05) and was increased in more severely affected patients (MMSE≤20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31) = 4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.

Melanin-laden macrophages in the CSF to diagnose Vogt-Koyanagi-Harada simulating ocular syphilis.

PURPOSE: To describe a case of Vogt-Koyanagi-Harada (VKH) disease initially presenting as ocular syphilis. METHODS: A 51-year-old woman presented with counting fingers vision in both eyes. She underwent a complete ophthalmic examination, serological testing, fluorescein angiography, and CSF analysis. RESULTS: Serological testing revealed positive titers for syphilis. Fluorescein angiography demonstrated findings suggesting VKH. CSF cytology showed macrophages containing melanin granules consistent with VKH. Subsequent treatment with corticosteroids and cyclosporine resulted in significant improvement of vision. CONCLUSION: The presence of melanin-laden macrophages within the CSF allows for the differentiation of VKH from ocular syphilis.

Vogt-Koyanagi-Harada disease presenting initially as aseptic meningoencephalitis.

Vogt-Koyanagi-Harada (VKH) disease in a Gypsy woman was diagnosed 4 months after her initial complaints. The delay is explained by the facts that: (1) the characteristic ophthalmological symptoms, which usually herald the disease and ensure early diagnosis, developed only late during the course; and (2) only retrospective analysis of the cerebrospinal fluid (CSF) cell preparation proved the presence of melanin-laden macrophages (MLMs), specific for the syndrome. We emphasize that VKH syndrome may initially present as aseptic meningitis, without specific ophthalmological symptoms. In suspected cases a very detailed CSF cell analysis is needed, because the presence of MLMs could confirm the diagnosis. However, VKH syndrome has a much higher incidence in Asia; cases in other races, including white people in Europe, also occur.