Methods
Subjects
We contacted 117 poisoned patients by phone to invite them to participate in the present study. We invited them to attend an outpatient clinic for a cognitive and psychiatric assessment in the Purpan hospital, Toulouse, France.
Patients were eligible for the study if they met the following criteria: 1) A diagnosis of CO poisoning according to the published criteria of documented exposure to carbon monoxide or obvious exposure to carbon monoxide with observation of any of the following symptoms: loss of consciousness, confusion, headache, malaise, fatigue, forgetfulness, dizziness, visual disturbances, nausea, vomiting, cardiac ischemia, or metabolic acidosis.[6] If the carboxyhemoglobin level was below 10 percent, the patient was eligible only if carbon monoxide poisoning was the only plausible diagnosis, 2) Above 15 years of age, 3) French language abilities good enough to undergo the assessment, 4) Signed informed consent. Non-inclusion criteria were: patients admitted to a nursing home, patients with a preexisting chronic neurological illness or with depression or post-traumatic stress disorder, patients with a life threatening condition and patients with hypoxia due to a chemical intoxication. Patients who suffered from any medical condition, other intoxication or brain traumatism between CO poisoning and the assessment in the present study were not included. When possible, carboxyhemoglobin (COHb) level was recorded. A CT scan was performed when necessary at the acute phase.
Procedure
The included patients were asked to fill out cognitive complaint and quality of life questionnaires.[10,11] They then underwent general and neurological clinical examinations, which included a semi-structured interview. A cognitive assessment derived from the Carbon Monoxide Neuropsychological Screening Battery was performed: Free and Cued Selective Reminding Test (FCSRT) for verbal episodic memory, WAIS-III Letter-Number Sequencing for working memory, MEM-III orientation test, WAIS-III Digit Symbol Test, TMT A and B, Stroop test for executive functions, and confrontation naming test for language.[4] In accordance with the literature, 8 specific variables of interest were identified within this battery: the cued and total 3 recall of the FCSRT (score/48), the raw score for Letter-Number Sequencing (/21), the raw score of the orientation test (/14), the raw score for digit substitution in the Digit Symbol Test (/133), time in seconds for TMT B-A, reading time in seconds for the score interference part of the Stroop test and the raw score for naming in the confrontation naming test (/10).[6–8] Psychiatric assessment was performed using subtests of the Mini International Neuropsychiatric Interview (M.I.N.I. 5.0.0): major depressive episode (MDE), manic episode, hypomanic episode, post-traumatic stress disorder (PTSD), psychotic disorders, and antisocial personality disorder.[12] The total time of the evaluation was approximately 1 hour.
A group of controls not exposed to carbon monoxide was enrolled in the study. They were relatives of patients seen in our memory clinic. They were paired 1:1 to patients for age, gender, and level of education. Controls received exactly the same evaluation tests as patients.
Patients and controls gave their informed consent for this study. The study was approved by the local ethics committee ("Comité d'Ethique de la Recherche" of the Toulouse teaching hospital "CHU de Toulouse", France).
Statistical Analysis
We performed an intergroup comparison on demographic and clinical data using bilateral Student t tests for independent samples, non-parametric Mann-Whitney U tests when a Kolmogorov-Smirnov test indicated that the sample did not follow a normal distribution, or a chi2 test when appropriate. Effect size was estimated using Cohen's D[13] when a significant difference was observed. Following conventional criteria, an effect size of 0.20 to 0.30 was considered "small", around 0.50 "medium" and above 0.80 "large". In the patients' group, we used Spearman correlation between COHb level and cognitive composite score. The cognitive composite score was generated from the 8 specific variables of interest previously identified (the cued and total 3 recall of the FCSRT, the raw score for Letter-Number Sequencing, the raw score for the orientation test, the raw score for digit substitution in the Digit Symbol Test, time in seconds for TMT B-A, reading time in seconds for the score interference part of the Stroop test and the raw score for naming in the confrontation naming test). For each of the 8 variables, the patients' scores were standardized according to the group average of the variable. Then, the cognitive composite score was calculated as the mean of the 8 standardized cognitive scores. The lower the cognitive composite score, the more severe the cognitive impairment. p < 0.05 was considered statistically significant.
BMC Neurol. 2014;14(153) © 2014 BioMed Central, Ltd.
