The association between pineal gland calcification and white matter hyperintensities of presumed vascular origin in older adults. A population-based study.

Pineal gland calcification (PGC) has been associated with low melatonin production, a hormone with anti-oxidant, anti-inflammatory, and neuro-protective effects. Therefore, melatonin deficiency may play a role in the development of cerebral small vessel disease (cSVD), a condition that is partly related to upregulation of oxidative and inflammatory mechanisms leading to endothelial dysfunction, breakdown of the blood-brain barrier, and impaired interstitial fluid drainage. In this study, the association between PGC (a surrogate for melatonin deficiency) and white matter hyperintensities (WMHs) of presumed vascular origin (a biomarker of cSVD) was assessed in Atahualpa cohort individuals aged ≥60 years undergoing head CT and brain MRI. PGC was rated as none-to-mild and moderate-to-severe. WMHs were classified according to the modified Fazekas scale. A logistic regression model was fitted to assess the independent association between moderate-to-severe PGC and WMHs. Inverse probability of exposure weighting was used to estimate the effect of PGC on WMH. Of 373 individuals, 96 (26%) had moderate-to-severe PGC and 86 (23%) had moderate-to-severe WMHs. Moderate-to-severe PGC and WMH were independently associated in a fully-adjusted logistic regression model (OR: 2.21; 95% C.I.: 1.19-4.11; p = 0.012). Inverse probability of exposure weighting showed an estimate for the proportion of moderate-to-severe WMH among those with none-to-mild PGC of 20.5%, and the exposure-effect was 13.2% higher among those with moderate-to-severe PGC (ß: 0.132; 95% C.I: 0.036-0.229; p = 0.007). The association found in this study provides grounds for further evaluation of the role of melatonin deficiency in cSVD development.

Midline Cava And Limbic System Dysfunction In Community-Dwelling Individuals Aged ≥20 Years Living In Rural Ecuador. A Case-Control Study Nested To A Population-Based Cohort / Cavum De Línea Media Y Disfunción Del Sistema Límbico En Individuos De 20 Años O Más Que Viven En Zonas Rurales Del Litoral Ecuatoriano. Estudio De Caso-Control Anidado En Una Cohorte Poblacional

ABSTRACT Background: Persistence of cavum septum pellucidum (CSP) and cavum vergae (CV) into adulthood and their association with mood disorders is unknown. Objective: We aimed to assess persistence of these cava in Atahualpa cohort individuals, and their association with clinical depression (as a surrogate of limbic system dysfunction). Methods: Cases were defined as Atahualpa residents aged ≥20 years with CSP and/or CV and paired 1:1 to age- and sex-matched randomly-selected controls. A board-certified psychiatrist (blinded to case-control status) interviewed individuals with the aid of the Patient Health Questionnaire depression module (PHQ-9) to establish a diagnosis of clinical depression. The McNemar's test and conditional logistic regression models were fitted to assess the independent association between persistence of CSP and/or CV and clinical depression (as the dependent variable). Results: Of 1,298 individuals undergoing a head CT, 51 (3.9%) had a CSP and/or CV. The selection process for the nested case-control study on the Atahualpa cohort (after excluding eight missing individuals with midline cava) generated 43 pairs. Nine of 43 case-patients (20.9%) and only two control subjects (4.7%) had moderate-to-severe scores on the PHQ-9 (cutoff ≥10 points). Clinical depression was significantly more frequent among case-patients than controls by the McNemar's test (OR: 8; 95% C.I.: 1.1 - 354.9) and the conditional logistic regression model (OR: 8; 95% C.I.: 1.00 - 63.96). Conclusions: This study provides epidemiological evidence favoring the association between midline cava and clinical depression, supporting their relationship with limbic system dysfunction.

RESUMEN Antecedentes: La persistencia de cavum septum pellucidum (CSP) y cavum Vergae (CV) en adultos y su asociación con trastornos del estado de ánimo es desconocida. Objetivo: Evaluar la persistencia de estas cavidades y su asociación con depresión clínica (como marcador de disfunción del sistema límbico). Métodos: Los casos se definieron como residentes de Atahualpa con edades ≥20 años con CSP y/o CV y se emparejaron 1:1 con controles aleatoriamente seleccionados de acuerdo con edad y sexo. Un psiquiatra (ciego al estado caso/control) entrevistó a los individuos con el módulo de depresión del cuestionario de salud del paciente (PHQ-9) para establecer diagnóstico de depresión clínica. La prueba de McNemar y modelos de regresión logística condicional se utilizaron para evaluar la asociación independiente entre persistencia de CSP y/o CV y depresión clínica (como variable dependiente). Resultados: De 1.298 individuos sometidos a TC de cerebro, 51 (3.9%) tenían un CSP y/o CV. El proceso de selección para el estudio de casos y controles generó 43 pares. Nueve de 43 casos (20.9%) y solo dos controles (4.7%) tuvieron puntajes de moderados a severos en el PHQ-9 (punto de corte ≥10 puntos). La depresión clínica fue significativamente más frecuente entre los pacientes que en los controles mediante la prueba de McNemar (OR: 8; 95% C.I.: 1.1 - 354.9) y la regresión logística condicional (OR: 8; 95% C.I.: 1.00 - 63.96). Conclusiones: Este estudio proporciona evidencia epidemiológica que favorece la asociación entre persistencia de CSP y/o CV y depresión clínica, lo que favorece su relación con disfunción del sistema límbico.

Supratentorial arachnoid cysts and seizures/epilepsy: A population study in community dwellers aged ≥20 years.

Literature on the association between arachnoid cysts and seizures/epilepsy is inconsistent, and most series have been flawed due to recruitment bias. In this study, we aimed to assess the prevalence of supratentorial arachnoid cysts (SACs) in Atahualpa residents aged ≥20 years, and to estimate whether these lesions were associated with seizures/epilepsy. A total of 1157 individuals were included. Computed tomography revealed SACs in 25 individuals (2.2%). Most had middle cranial fossa SACs (n = 19). Recurrent nonprovoked seizures were diagnosed in 28 individuals and a single seizure in 4. Only 1 of 25 (4%) individuals with SACs had seizures/epilepsy as opposed to 31 of 1132 (2.7%) who did not have SACs (P = 0.508). A logistic regression model showed no association between SACs and seizures/epilepsy, after taking into account the effect of relevant confounders (odds ratio [OR] 1.71; 95% confidence interval [95% CI] 0.22-13.3; P = 0.607). This study provides evidence of lack of association between SACs and seizures/epilepsy.

Calcified Neurocysticercosis and Headache in an Endemic Village: A Case-Control Study Nested to a Population-Based Cohort.

Headache in patients with calcified neurocysticercosis (NCC) is probably common but has been largely overlooked. We aimed to assess the presence, characteristics, and diagnosis of headache across patients with calcified NCC and their matched controls. In this case-control study nested to a population-based cohort, Atahualpa residents aged ≥ 20 years with calcified NCC were identified as case patients and paired 1:1 to age- and gender-matched randomly selected controls. A culturally adapted questionnaire was derived from the EUROLIGHT. Headache diagnosis was established according to the International Classification of Headache Disorders, 3rd edition. Conditional logistic regression models for matched paired data were fitted to assess the independent association between calcified NCC (as the exposure) and headache variables, after adjusting for education, alcohol intake, depression, and epilepsy. The selection process generated 106 case patients and their matched controls. Lifetime headache prevalence (odds ratio [OR]: 4.18; 95% Confidence Interval [CI]: 1.79-9.75; P = 0.001), current headaches (OR: 4.19; 95% CI: 1.92-9.16; P < 0.001), and intense headaches (OR: 9.47; 95% CI: 2.88-31.19; P < 0.001) were more frequent among cases than in controls. In addition, migraine (but not other forms of headache) was more frequent among subjects with calcified NCC (OR: 4.89; 95% CI: 2.36-11.39; P < 0.001). This study shows a robust epidemiological association between headache-particularly migraine-and calcified NCC.

EEG Patterns in Patients With Calcified Neurocysticercosis With or Without Hippocampal Atrophy.

PURPOSE: To assess whether hippocampal atrophy develops in conjunction with clinical or subclinical epileptiform or encephalopathic activity in subjects with neurocysticercosis (NCC). METHODS: Using a population-based and nested case-control study design, scalp EEGs and brain MRIs were performed in Atahualpa residents aged ≥40 years, who have imaging-confirmed NCC (case patients), as well as in age- and sex-matched NCC-free control subjects. RESULTS: Sixty-two case patients and 62 control subjects were included. Encephalopathic EEG patterns were more common in five NCC subjects with epilepsy than in those without a history of seizures. Epileptiform EEG activity was noted in one patient with NCC but in none of the control subjects. This subject's focal epileptiform discharges correlated with the location of calcified cysticerci in the brain parenchyma, and the hippocampus ipsilateral to the epileptiform discharges was more atrophic than the contralateral hippocampus. The degree of hippocampal atrophy in patients with NCC without a history of seizures was significantly greater than in control subjects (P < 0.01) and tended to be even greater in patients with NCC with a history of seizures. CONCLUSIONS: Hippocampal atrophy may not be exclusively related to seizure activity in patients with NCC. Other mechanisms, such as recurrent bouts of inflammation around calcified cysticerci, might explain the association between NCC and hippocampal atrophy.

Búsqueda de substitutos para estudios de neuroimagen con propósitos de investigación: Experiencia del Proyecto Atahualpa / The search of surrogates for neuroimaging studies for research purposes: The Atahualpa Project Experience

RESUMEN El diagnóstico de muchas de las enfermedades neurológicas no transmisibles requiere de la práctica de una resonancia magnética, la cual no se encuentra disponible en regiones rurales o remotas. Es importante realizar esfuerzos destinados a encontrar pruebas diagnósticas portátiles que sirvan como tamizaje para la identificación de personas que necesitan ser sometidas a una IRM. Como parte del Proyecto Atahualpa, hemos invitado a todos los participantes ≥60 años para la práctica de una IRM de cerebro y aproximadamente el 80% de las personas han aceptado el procedimiento. Por lo tanto, tenemos la oportunidad única de probar la validez de pruebas no-invasivas que puedan ser utilizadas como substitutos de resonancia para identificar candidatos a hacerse dicho examen. Hasta la fecha, hemos estudiado el valor del índice tobillo-brazo, la confiabilidad de la relación neutrófilos-linfocitos, la exactitud de la presencia de retinopatía hipertensiva y el valor del Doppler transcraneal para la detección de personas con enfermedad de pequeño vaso cerebral. Los individuos con índice tobillo-brazo anormal tiene 4 veces más riesgo de tener un infarto lacunar silente que aquellos con índice normal. Una relación neutrófilos-linfocitos elevada es pobremente sensitiva pero altamente específica para detectar personas con por lo menos un marcador de imagen de enfermedad de pequeño vaso. Los individuos con retinopatía hipertensiva Grados 2-3 tienen casi 4 veces más riesgo de tener hiperintensidades de sustancia blanca que aquellos con retinopatía Grado 1 o sin retinopatía. Finalmente, la correlación del índice de pulsatilidad de las arterias intracraneales para detectar marcadores de enfermedad de pequeño vaso es pobre. Seguimos en la búsqueda de una prueba económica y confiable que permita la identificación de sujetos aparentemente sanos, con riesgo de desarrollar eventos cerebrovasculares catastróficos.

ABSTRACT Diagnosis of many non-communicable neurological diseases require the use of MRI, which is not readily available in remote rural populations. Efforts should be directed to find portable screening diagnostic tools that may help identify candidates for MRI screening. In the Atahualpa Project, all participants aged ≥60 years have been invited for the practice of MRI, and about 80% of them have underwent the procedure. Therefore, we have the unique opportunity to test the accuracy of non-invasive exams to be used as surrogates to MRI for identifying candidates for the practice of this exam. To date, we have assessed the value of the ankle-brachial index ABI), the reliability of the neutrophil-to-lymphocyte ratio (NLR), the accuracy of hypertensive retinopathy, and the value of transcranial Doppler (TCD) to detect individuals with cerebral small vessel disease. Individuals with an abnormal ABI have 4 times de odds of having a silent lacunar infarct than those with a normal ABI. A high NLR has a poor sensitivity but is highly specific for detecting persons with at least one imaging signature of small vessel disease. Individuals with hypertensive retinopathy Grades 2-3 are almost four times more likely to have moderate-to-severe white matter hyperintensities than those with no- or only Grade 1 retinopathy. Finally, the correlation between the pulsatility indexes of major cerebral arteries with imaging markers of small vessel disease, as assessed by TCD, was poor. We are still in the search of some non-expensive and readily available biomarker that allow the identification of apparently healthy persons at risk of suffering a catastrophic cerebrovascular event.