Evaluation of structural variations in the pituitary gland, hormonal status and laboratory markers of the central nervous system functioning in patients with chronic disorders of consciousness

Abstract

BACKGROUND: Consciousness is the state of being awake and aware of oneself and the environment. The disorders of consciousness result from pathologies that impair awareness. The development of effective comprehensive personalized interventions contributing to the recovery of consciousness in patients with chronic disorders of consciousness is one of the most pressing and challenging tasks in modern rehabilitation.

AIM: The aim of this study was to understand structural problems of the pituitary gland, blood levels of gonadotropins and melatonin as well as brain damage markers in the blood and cerebrospinal fluid in patients with chronic disorders of consciousness and to analyze the levels of the above markers among different groups of patients depending on the level of impaired consciousness.

MATERIALS AND METHODS: We examined 61 chronic disorders of consciousness patients and identified three groups depending on the level of consciousness including 24 patients with unresponsive wakefulness syndrome, 24 patients with a minus minimally conscious state, and 13 patients with minimally conscious state plus. We performed magnetic resonance imaging of chiasmatic-sellar region and determined blood serum levels of follicle-stimulating and luteinizing hormones and melatonin, as well as urinary level of 6-sulfatoxymelatonin and the content of brain derived neurotrophic factor (BDNF), apoptosis antigen (APO-1), FasL, glutamate, and S100 protein in the blood serum and cerebrospinal fluid.

RESULTS: The patients were examined in the age ranging from 15 to 61 years old. Patient groups were homogeneous by the level of consciousness in terms of age and duration of chronic disorders of consciousness by the time of examination. The patients did not differ in the pituitary volume regardless of the level of consciousness. No significant differences were found between the groups with different levels of consciousness when studying the levels of melatonin in the blood serum and its metabolite in the urine. A peak in melatonin secretion was detected at 3 a.m. in 54.5 % of the patients, which can be considered as a favorable prognostic marker for further recovery of consciousness. Hypogonadotropic ovarian failure was found in 34 % of the patients, with normogonadotropic ovarian failure in the remaining patients. Serum APO-1 and BDNF levels were significantly higher in patients with minimally conscious state relative to those with unresponsive wakefulness syndrome. Significantly lower levels of glutamate in the cerebrospinal fluid were detected in women with unresponsive wakefulness syndrome compared to patients with minimally conscious state.

CONCLUSIONS: Further in-depth examination and accumulation of data on patients with chronic disorders of consciousness may provide an opportunity to identify highly informative markers for predicting outcomes and to develop new effective approaches to rehabilitation of consciousness in this category of patients.

Keywords

chronic disorders of consciousness / minimally conscious state / gonadotropic function / ovarian failure / magnetic resonance imaging of chiasmatic-sellar region / brain-derived neurotrophic factor / apoptosis antigen APO-1 / FasL / glutamate / S100 protein

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