Jm Minderhoud

NEUROTRANSMITTERS IN THE TREATMENT OF PATIENTS WITH SEVERE HEAD-INJURIES

Results of treatment with L-dopa and/or physostigmine of patients with severe head injuries were examined and discussed. This treatment given to patients still unconscious a long period after trauma resulted in clinical improvement in 29 of the 45 trials (64%). Results were poor in patients with a low motor score and no paradoxical response on the caloric oculogram. In nearly all patients motor activity increased, but did not always result in clinical improvement. The results were explained by the presence of functional, reversible dysfunctions present in the majority of patients in the course of recovery.

The effect of gonadectomy on the clinical course of chronic experimental allergic encephalomyelitis

Experimental allergic encephalomyelitis (EAE) is an animal model for the human neurological disease multiple sclerosis (MS). Upon immunization with guinea pig spinal cord under a low dose of Cyclosporin A, male Lewis rats develop a severe chronic (relapsing) course of EAE (CR-EAE). By contrast, female Lewis rats develop a more mitigated course of EAE: only half of the female rats develop relapses. To further analyze factors determining this sexual dimorphism in the course of EAE, in the present study male and female Lewis rats were gonadectomized before induction of CR-EAE. Now both male and female rats all developed a severe chronic course of EAE, showing extensive pathological changes in the CNS. In the female sham-gonadectomy (control) group only one third of the rats developed relapses. These female rats only showed mild pathological changes in the CNS. In the male sham-gonadectomy (control) group all rats developed relapses of EAE and showed extensive pathological changes in the CNS. From these data we conclude that the presence of the ovaries (partially) protects female rats against relapses of EAE and CNS injury. Presence or absence of the testes apparently makes no difference on the course of EAE. We propose that sex hormones produced in the ovaries protect female rats against relapses of EAE and underlying CNS injury.

THE PATTERN OF RECOVERY AFTER SEVERE HEAD-INJURY

The pattern of recovery after head injury was studied on the basis of clinical data on 200 patients. An unmistakable pattern was found in which it was possible to distinguish between symptoms of only short duration (due to the unfavourable prognosis, among other things), symptoms which showed a fairly quick recovery such as the E score and the oculovestibular response, and symptoms characterized by a longer interval between the accident and their recovery. A clear difference was found between the pattern recovery of E scores and oculovestibular response on the one hand, and recovery of M and V scores on the other. The implications of the pattern of recovery thus established, are discussed.

On the nature of brain stem disorders in severe head injured patients

SummaryIn head injured patients changes were found in the CSF levels of metabolites of the dopaminergic and the serotonergic neurotransmission (HVA and 5-HIAA). After the fifth, day following trauma a significant derease of the HVA levels in the lumbar CSF after probenecid treatment was found. The intensity of this decrease was found to be related to the severity of the trauma (period of unconsciousness), but not to the state of consciousness.Also the probenecid-induced 5-HIAA levels in conscious patients were decreased after the fifth post-traumatic day. In unconscious patients, however, an increased turnover of serotonin was found to be also related to the period of unconsciousness, particularly in the period of 5–20 days after trauma. Between 21 and 60 days after trauma the 5-HIAA concentrations in unconscious patients decreased remarkably, but they were still significantly higher than in the conscious patients. It can be concluded that during unconsciousness serotonergic neurons have a high rate of turnover, but that both neurotransmitter systems are damaged by the direct or indirect consequences of the injury.

On the nature of brain stem disorders in severe head injured patients. II. A study on caloric vestibular reactions and neurotransmitter treatment.

SummaryThe results of eleotro-oculographic recordings made after caloric vestibular stimulation (C.O.G.) in severe head injured patients are discussed. It was found that:1.The C.O.G. correlates with the state of consciousness of the patients.2.The rate of improvement of the C.O.G. correlates with the rate of the clinical improvement.3.A prediction of the duration of unconsciousness can be made by repeated C.O.G. scores as well as by repeated scoring of the clinical state.4.In all patients a paradoxical response is present except in those who have regained clear consciousness and in those persisting in a vegetative state, so the presence of a paradoxical response indicates the possibility of further improvement. It was supposed that in patients with a paradoxical response a functional brain dysfunction was present, which was at least partly caused by disturbed neurotransmitter metabolism. Therapeutic trials with L-DOPA and physostigmine were successful in patients with a paradoxical response, but without any result in those without this phenomenon. The responses to L-DOPA and to physostigmine are related respectively to motor pattern and to verbal or non-verbal communication.

5-hydroxyindoleacetic acid (5-HIAA) levels in the cerebrospinal fluid in consciousness and unconsciousness after head injury

Abstract Concentrations of 5-hydroxyindoleacetic acid (5-HIAA) were determined in the lumbar cerebrospinal fluid (CSF) of patients after head injury. Unconscious patients showed after the fifth posttraumatic day no significant difference with the control group. The conscious patients showed significantly decreased 5-HIAA levels compared with the control group (following probenecid administration) as well as compared with the unconscious patients. These results suggest a relatively high cerebral serotonin turnover during the state of unconsciousness after head injury in man.

ELECTRO-OCULOGRAPHIC STUDY OF CALORIC VESTIBULAR REACTIONS IN PATIENTS WITH SEVERE HEAD-INJURIES .1. ELECTRO-OCULOGRAPHY AS A METHOD TO PREDICT OUTCOME

In this study electro-oculographic recordings were made after caloric vestibular stimulation (C.O.G.) in 42 patients with severe head-injuries. The curves with eyes open and the changes when eyes were closed were evaluated and scored. A correlation was found between the C.O.G. and the state of consciousness but only the degree of improvement of the C.O.G. showed a good correlation with the clinical improvement. The presence of a paradoxical response in patients with a prolonged coma was found to predict possibilities of further improvement. It was proposed that in the patients with a paradoxical response a rather diffuse biochemical dysfunction of the brain-stem was present, which could be influenced by treatment. In the second part of this study the results of the trials with a treatment with L-Dopa and physostigmine are given. It was found that patients in a vegetative state or in a state of prolonged coma could be stimulated with the therapy only when the paradoxical response had been present. L-Dopa and physostigmine respectively improved the motor pattern and the contact activities.