Neuropsychiatric phenotypes of anti-NMDAR encephalitis: a prospective study.

BACKGROUND: Patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments. METHODS: A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF. RESULTS: After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia-delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia. CONCLUSIONS: Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia-delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE.

Neurocognitive function in adult residents of a mining district in Mexico after reducing manganese exposure: Follow-up after 11 years.

BACKGROUND: Little is known about the neurotoxic effects of chronic exposure to airborne Mn once exposure has been reduced. The environmentally exposed and the reference adult populations evaluated in 2002 were followed, after an environmental management program (EMP) was implemented to reduce the exposure in a mining district in Mexico. OBJECTIVE: The aim of this study was to compare the association between exposure to Mn and neurocognitive performance in environmentally exposed and reference groups of adults before and after EMP implementation. METHODS: In 2013, the same battery of neurocognitive tests used in the initial study (2002) was applied to 58 adults exposed to airborne Mn and 30 adults from the reference community. A cumulative exposure index (CEI) was estimated for the study population before and after the EMP. Categorical outcomes were analyzed using logistic regression, and the resulting ORs were compared between studies. Continuous outcomes were analyzed using linear regression. All models were adjusted for age, years of education, socioeconomic status and blood lead levels. RESULTS: Exposed adults from the post-EMP study showed an improvement in fine motor and verbal regulation of motor skills (OR < 1) compared to the exposed adults from the pre-EMP study (OR > 1). In both pre- and post-studies, the exposed adults showed a deterioration in their dynamic organization of motor activity compared to the reference group (p < 0.05); however, they showed no significant change in attention and working-memory performance. DISCUSSION: After four years of a significant reduction in airborne Mn levels resulting from EMP implementation, chronically exposed adults showed an improvement in fine motor and verbal regulation of motor skills; however, the remaining areas of their motor and cognitive functions remained impaired.

Effect of environmental manganese exposure on verbal learning and memory in Mexican children.

Manganese (Mn) is an essential metal, but in excess it becomes neurotoxic. Children's developing nervous system may be especially vulnerable to the neurotoxic effects of overexposure to this metal. The aim of this study was to assess the effect of Mn exposure on verbal memory and learning in 7- to 11-year-old children. We tested 79 children living in the Molango Mn-mining district and 95 children from a non-exposed community in the same State of Mexico. The Children's Auditory Verbal Learning Test (CAVLT) was administered. Blood and hair samples were obtained to determine Mn concentrations using atomic absorption spectrophotometry. CAVLT performance was compared between the two groups and multilevel regression models were constructed to estimate the association between biomarkers of Mn exposure and the CAVLT scores. The exposed group presented higher hair and blood Mn (p<0.001) than the non-exposed group (median 12.6 vs. 0.6µg/g, 9.5vs. 8.0µg/L respectively), as well as lower scores (p<0.001) for all the CAVLT subscales. Hair Mn was inversely associated with most CAVLT subscales, mainly those evaluating long-term memory and learning (ß=-0.47, 95% CI -0.84, -0.09). Blood Mn levels showed a negative but non-significant association with the CAVLT scores. These results suggest that Mn exposure has a negative effect on children's memory and learning abilities.

Serum prolactin rises in Mexican school children exposed to airborne manganese.

Early studies on manganese (Mn) exposure have shown that this transition metal affects dopamine neurotransmission. Dopamine serves as a tonic inhibitor of prolactin release in the anterior hypophysis, thus the serum prolactin levels in occupationally Mn exposed workers has been found increased. However, little is known about environmental Mn exposure effect on this hormone. In the present study we assessed serum prolactin in environmentally (mainly through air) exposed children living in the proximity of a rich Mn zone in Mexico and a control group with similar socioeconomic and ethnic characteristics. We also determined Mn levels in blood and hair, hemoglobin and anthropometric variables. Children between 7 and 11 years old were included (77 from Mn exposed and 93 from control communities). Blood Mn was higher in exposed children (median 9.5 µg/L, rank [5.5, 18]) as compared to the control group (median 8 µg/L, rank [5, 14]) (p<0.05, Mann-Whitney). Hair Mn was also increased in the exposed group (median 13.2 µg/g, rank [4.2, 48]) in comparison to the control group (median 0.6 µg/g rank [0.06, 3.6]). Prolactin was found increased in the exposed children (median 12.35 ng/ml, rank [2.90, 33.70]) versus controls (median 7.77 ng/ml, rank [2.7, 23.6]). Positive correlations were found between prolactin and both blood Mn and hair Mn (Rho=0.217 and 0.250, respectively, p<0.05). A linear regression, with prolactin as the dependent variable, showed hair Mn as the determinant variable after adjusting by age, hemoglobin and sex. After a stratification of hair and blood Mn into low, medium and high content, significant associations were also found, confirming the relationship between prolactin and hair Mn. Results suggest that children from these Mn environmentally exposed communities could be at risk of endocrine alterations.

Environmental exposure to manganese and motor function of children in Mexico.

OBJECTIVES: Occupational manganese (Mn) exposure has been associated with motor deficits in adult workers, but data on the potential effects of environmental exposure to Mn on the developing motor function for a children population is scarce. The aim of this study was to evaluate the association between exposure to Mn and motor function of school aged children. METHODS: We conducted a cross-sectional study selecting 195 children (100 exposed and 95 unexposed) between 7 and 11 years old. The following tests were used to evaluate the motor function: Grooved pegboard, finger tapping, and Santa Ana test. Mn exposure was assessed by blood (MnB) and hair concentrations (MnH). We constructed linear regression models to evaluate the association between exposure to Mn and the different test scores adjusting for age, sex, maternal education, hemoglobin and blood lead. RESULTS: The median concentration of MnH and MnB was significantly higher in exposed (12.6 µg/g and 9.5 µg/L) compared to unexposed children (0.6 µg/g and 8.0 µg/L). The exposed children on average performed the grooved pegboard test faster, but made more errors, although these results did not reach statistical significance with neither one of the Mn exposure biomarkers. MnB showed an inverse association on the execution of the finger tapping test (average in 5 trials ß -0.4, p=0.02), but no association was observed with MnH. CONCLUSIONS: A subtle negative association of Mn exposure on motor speed and coordination was shown. In adults, the main effect of environmental Mn exposure has been associated with motor skills, but these results suggest that such alterations are not the main effect on children.