CSF neurotransmitter metabolites and short-term outcome of patients in coma after head injury

Abstract

The main metabolites of the neurotransmitters noradrenaline, dopamine, and serotonin, methoxy-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) respectively, were estimated by HPLC with electrochemical detection in CSF samples from 24 patients in coma after head injury, 1 to 12 (mean 3.0) days from accident, and from 24 age- and sex-matched subjects undergoing myelography for possible herniated disk. Analysis of variance with age as covariate, revealed significantly elevated levels of all three metabolites in the patients group. The concentrations of 5HIAA were negatively correlated to the score in the Glasgow Coma Scale. Fourteen patients who recovered with no or minor neurological deficits, had significantly lower CSF 5HIAA levels compared to the ten patients who had a bad outcome (death), while there were no differences regarding HVA or MHPG concentrations. The possibility of a connection of the high neurotransmitter turnover during coma to the development of post-traumatic depression is discussed.

Stimulants and Acetylcholinesterase Inhibitors for the Treatment of Cognitive Impairment After Traumatic Brain Injury

“…Cerebrospinal fluid sampling of catecholamine metabolites in persons with recent severe TBI indicates that levels of these neurotransmitters are elevated in the immediate post-injury period. 8,9 The duration of these elevations generally is brief, with normalization occurring during the acute recovery period. 8,9 The role of catecholaminergic dysfunction in the development of persistent post-traumatic cognitive impairment is not clearly established.…”

“…8,9 The duration of these elevations generally is brief, with normalization occurring during the acute recovery period. 8,9 The role of catecholaminergic dysfunction in the development of persistent post-traumatic cognitive impairment is not clearly established. Preliminary findings from studies pairing pharmacologic probes (i.e., dopaminergic agonists and alpha-2 adrenergic agonists) with functional magnetic resonance imaging in the laboratory of McAllister and colleagues suggest that catecholaminergic dysregulation plays a role in post-traumatic working memory impairments.…”

Stimulants and Acetylcholinesterase Inhibitors for the Treatment of Cognitive Impairment After Traumatic Brain Injury

“…6 Optimal levels enhance processing of contextually relevant cognitive, emotional, or behavioral information (signal) and inhibit processing of background information (noise). 8,9 The duration of these elevations generally is brief, with normalization occurring during the acute recovery period. The effects of catecholamines on cerebral information processing follow an inverted U-shaped dose-response curve.…”

“…Increasing the signal-to-noise ratio in cerebral information processing systems generally is manifested clinically as an improvement in the speed and/or efficiency of cognition. 8,9 The role of catecholaminergic dysfunction in the development of persistent post-traumatic cognitive impairment is not clearly established. Accordingly, either deficient or excessive dopamine may interfere with such processing.…”

CSF Neurotransmitter metabolites in comatose head injury patients during changes in their clinical state

“…Studies in patients in coma after severe head injury have shown increased concentrations of methoxyhydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA), the main metabolites of NA, 5HT, and DA, respectively [4,5,7,10]. In a previous publication [7], we reported increased concentrations of MHPG, 5HIAA, and HVA in CSF of a group of 24 patients in coma after severe head injury, compared with data from patients undergoing myelography for possible herniated disc. Higher 5HIAA concentrations were found in the patients who had a bad outcome compared to those with a good outcome.…”