This article was downloaded by: [York University Libraries] On: 10 November 2014, At: 19:07 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK

Applied Neuropsychology: Adult Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/hapn21

Neuropsychological Performance in Patients With Carbon Monoxide Poisoning a

b

Zai-Ting Yeh , Chung-Fen Tsai , Ping-Keung Yip e

Yuan Chen & Lan-Yu Kung

c d

a

b

, Chiao-Yu Lo , Su-Min Peng , Shao-

e

a

Department of Clinical Psychology , Fu Jen Catholic University , New Taipei City , Taiwan

b

Department of Neurology , Cardinal Tien Hospital , New Taipei City , Taiwan

c

School of Medicine, Fu-Jen Catholic University , Taipei , Taiwan

d

Department of Neurology, Cardinal Tien Hospital and School of Medicine , Fu Jen Catholic University , New Taipei City , Taiwan e

Department of Hyperbaric Medicine , Cardinal Tien Hospital , New Taipei City , Taiwan Published online: 18 Oct 2013.

To cite this article: Zai-Ting Yeh , Chung-Fen Tsai , Ping-Keung Yip , Chiao-Yu Lo , Su-Min Peng , Shao-Yuan Chen & Lan-Yu Kung (2014) Neuropsychological Performance in Patients With Carbon Monoxide Poisoning, Applied Neuropsychology: Adult, 21:4, 278-287, DOI: 10.1080/23279095.2013.811670 To link to this article: http://dx.doi.org/10.1080/23279095.2013.811670

PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions

APPLIED NEUROPSYCHOLOGY: ADULT, 21: 278–287, 2014 Copyright # Taylor & Francis Group, LLC ISSN: 2327-9095 print=2327-9109 online DOI: 10.1080/23279095.2013.811670

Neuropsychological Performance in Patients With Carbon Monoxide Poisoning Zai-Ting Yeh Department of Clinical Psychology, Fu Jen Catholic University, New Taipei City, Taiwan

Downloaded by [York University Libraries] at 19:07 10 November 2014

Chung-Fen Tsai Department of Neurology, Cardinal Tien Hospital, New Taipei City, Taiwan

Ping-Keung Yip Department of Neurology, Cardinal Tien Hospital, and School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

Chiao-Yu Lo Department of Clinical Psychology, Fu Jen Catholic University, New Taipei City, Taiwan

Su-Min Peng Department of Neurology, Cardinal Tien Hospital, New Taipei City, Taiwan

Shao-Yuan Chen and Lan-Yu Kung Department of Hyperbaric Medicine, Cardinal Tien Hospital, New Taipei City, Taiwan

This study investigated changes in cognitive function in acute and delayed carbon monoxide (CO) poisoning groups with comprehensive neuropsychological tests at 1 month and 6 months after therapy. For this study, 11 patients with acute and 14 with delayed CO poisoning were recruited. The neuropsychological tests included psychomotor speed, visual-spatial ability, language, logical memory, working memory, and executive function. The results showed that patients with delayed neuropsychiatric syndrome (DNS) had poorer performance on neuropsychological tasks than did those with acute CO poisoning at the 1st month and reached almost the same level as the acute group on the neuropsychological tasks at the 6-month follow-up assessment. The DNS group had more significant progress on general cognitive function, psychomotor speed, and visual-spatial ability than did the acute group after continuous hyperbaric-oxygen therapy.

Key words:

carbon monoxide poisoning, delayed neuropsychiatric sequelae, neuropsychological tests, psychomotor speed INTRODUCTION

Address correspondence to Zai-Ting Yeh, Department of Clinical Psychology, Fu Jen Catholic University, 510 Chung Cheng Road, Hsinchuang, New Taipei City, 24205, Taiwan. E-mail: yehzt@ mail.fju.edu.tw

Exposure to carbon monoxide (CO), which excludes oxygen from the tissues through the formation of a reversible complex carboxyhemoglobin (COHb), can damage the cardiovascular and central nervous systems. The acute symptoms reported by patients include

Downloaded by [York University Libraries] at 19:07 10 November 2014

COGNITIVE FUNCTION AND CARBON MONOXIDE POISONING

headache, weakness or lethargy, dizziness, nausea, shortness of breath, chest pain, visual changes, and muscle cramping. Weaver and colleagues (2002) recruited 152 patients with CO poisoning and found that 85% of them had the symptoms of headache, 59% had dizziness, 63% had nausea, and up to 45% had cognitive problems with memory, attention, and concentration. Patients with a loss of consciousness or with COHb levels greater than 25% frequently show cognitive dysfunction lasting 1 month or longer (Goldstein & Goldstein, 2008; Weaver et al., 2002). Slowness of movement and progressive memory impairment are the primary chronic symptoms in patients with CO poisoning. Sohn, Jeong, Kim, Im, and Kim (2000) reported two CO poisoning cases that resulted in CO-induced Parkinsonism (COIP), which includes reduced facial expressions, reduced arm swings, bradykinesia, and rigidity. COIP slows processing speed and reduces motor function due to white-matter damage (Sohn et al., 2000). Gale and Hopkins (2004) recruited 20 patients with CO poisoning whose mean COHb was 26.0% and conducted neuropsychological assessments. They found that impairment of verbal memory and visual memory was related to a reduced hippocampus volume in patients with CO poisoning (Gale & Hopkins, 2004). Even 6 months or longer after CO poisoning, these cognitive deficits remained. Recently, a survey by Chang and colleagues (2010) revealed that in 9 patients with CO exposure, verbal episodic memory, visual memory, and visual-spatial ability were still impaired after 3 and 10 months. Other types of behavioral dysfunction have also been found, including mood disturbances, personality changes, and dementia (Chang et al., 2010; Hopkins & Weaver, 1995). Neuropsychiatric deterioration may occur for several days following CO poisoning. The symptoms, including cognitive and personality changes, psychic akinesia, amnesia, apathy, mutism, and irritable distractibility, have been documented in many case reports (Bryer, Heck, & Reams, 1988; Grattan, Eslinger, & Faust, 1988; Heinrichs, 1990; Sohn et al., 2000; Vicente, 1980) and in a few research studies (Amitai, Zlotogorski, Golan-Katzav, Wexler, & Gross, 1998; Gale & Hopkins, 2004; Gale et al., 1999). However, few studies have investigated executive dysfunction, which involves the prefrontal lobe, an area that is vulnerable to hypoxic injury after CO exposure (Gale & Hopkins, 2004). Moreover, as far as we know, no studies have systematically surveyed the degree of improvement in different cognitive domains between patients with acute neuropsychological sequelae (ANS) and with delayed neuropsychiatric sequelae (DNS). Two types of CO intoxication have been reported in clinical studies—ANS and DNS. Some patients with

279

CO poisoning may not have acute signs of cerebral symptoms. DNS are defined as development symptoms including headache, difficulty concentrating, lethargy, emotional lability, amnesia, psychosis, and Parkinsonism after an interval of 2 to 240 days after CO poisoning (Amitai et al., 1998). The syndrome is estimated to occur in 10% to 35% of victims. Pepe and colleagues (2011) found that of 141 patients with CO poisoning, 34 were diagnosed with DNS (24.1%), and 85.3% of these patients with DNS still reported cognitive impairment at 6-month follow-up visits (Pepe et al., 2011). The abnormal regions of DNS commonly involve the globus pallidus, hippocampus, frontal lobe, and the deep white matter, as determined by computed tomography, magnetic resonance imaging (MRI), and single photon-emission computed tomography (SPECT; Ernst & Zibrak, 1998; Min, 1986; Zagami, Lethlean, & Mellick, 1993). The standard treatment for CO poisoning includes removal from the site of exposure, administration of supplemental oxygen, and general support care. Administration of 100% oxygen at pressures higher than one atmosphere (hyperbaric oxygen, HBO) increases the dissolved-oxygen content in the blood, hastens the elimination of COHb, and decreases cerebral edema, which can cause central nervous system sequelae (Goldstein & Goldstein, 2008). Thus, HBO therapy is often recommended for patients with acute CO poisoning, especially if they have lost consciousness or have severe poisoning symptoms such as weakness, lethargy, dizziness, nausea, and confusion (Stoller & Stoller, 2007). Parkinsonism features such as bradykinesia and rigidity are common neurological sequelae in patients with DNS poisoning. Some evidence from MRI and diffusion tensor imaging studies has indicated periventricular white-matter atrophy, which may be reflected in psychomotor performance even 10 months after CO intoxication. Hippocampal atrophy after CO intoxication, which may be reflected in memory function, was also found in a study employing quantitative MRI and SPECT (Chang et al., 2010; Gale et al., 1999). Therefore, based on previous reviews, the first hypothesis of the present study was that the DNS group would have poorer performance on psychomotor speed and memory function compared with the ANS group at the 1st month after HBO therapy. The second hypothesis was that the DNS group would improve more on these neuropsychological tests compared with the ANS groups at 6-month follow up. The cognitive domains examined in the present study included psychomotor speed, visual-spatial abilities, language, logical memory, working memory, and executive function.

280

YEH ET AL.

METHOD

Downloaded by [York University Libraries] at 19:07 10 November 2014

Participants From May 11, 2007, to June 15, 2011, the neurology clinic and hyperbaric medicine center at Cardinal Tien Hospital in Taipei, Taiwan, referred a total of 30 patients with moderate-to-severe accidental CO poisoning for treatment. The causes of CO exposure were heating system combustion in a confined space (15 patients), charcoal burning (8 patients), and occupational exposure (7 patients). Twenty-five of these participants (14 men and 11 women) completed the follow-up measurement. Because of the small sample size, post-hoc power analysis is reported to ensure significant differences between groups. The study was approved by the Cardinal Tien Hospital Institutional Review Board and was conformed to institutional guidelines for the protection of human subjects. Patients with Mini-Mental State Examination (MMSE) scores >24 (Folstein, Folstein, & McHugh, 1975) signed informed consent forms before entering the trial, and the next of kin signed for those who had MMSE scores
24. The inclusion criterion for moderate-to-severe poisoning was a change in consciousness, and the exclusion criteria were hemodynamic compromise, pregnancy, or lack of informed consent. The patients were given initial HBO treatment sessions of 100% oxygen at three atmospheres for 120 min. For subsequent HBO sessions, we adjusted pressure to 2.5 atmospheres to reduce the possibility of oxygen toxicity. Comprehensive neuropsychological tests were used to evaluate the cognitive function of these patients at 1 month and 6 months after HBO treatment. The demographic data of the patients with acute and delayed CO poisoning are presented in Table 1. DNS were defined as development symptoms including headache, difficulty concentrating, lethargy, emotional lability, amnesia, psychosis, and Parkinsonism after an interval of 2 to 240 days after CO poisoning. The means of interval days in the DNS group is 29.08 in the present study. There were no differences in sex ratio, age, or education variables between the groups. The acute group had higher COHb levels compared with the delayed group,

but this was not significant. Before HBO treatment, 63.15% of patients had lost consciousness, and 36.84% were in a confused state. There was no significant difference in the numbers of HBO treatment between the acute and delayed groups. Neuropsychological Assessment The neuropsychological tests used included tests of seven domains: basic general cognitive, language, psychomotor speed, visual-spatial ability, logical memory, working memory, and executive function. The MMSE and the Cognitive Abilities Screening Instrument (CASI) were used for the general cognitive assessment. The Purdue Pegboard Task was used as the index of psychomotor speed, and the Block Design subtest of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) was used as the visual-spatial function index. The language function was measured with the verbal subtests of the WAIS-III, which include Information and Similarities. The Logical Memory test of the Wechsler Memory Scale-Third Edition (WMS-III) was used as the memory index. The Digit Span and Arithmetic tests in the Wechsler batteries were used as the working-memory index. The Chinese version and norm of the WAIS-III (Chen & Chen, 2002) and WMS-III (Hua, Chang, Lin, Yung, & Chen, 2005) were used for the assessment and subsequent data analyses. Executive function was measured with the Wisconsin Card-Sorting Test (WCST), Verbal Fluency, and the Trail-Making Test (TMT) Parts A and B. The scores of the WAIS-III and WMS-III were transformed into scale scores according to the norm of the Chinese population (Chen & Chen, 2002; Hua et al., 2005); the scale scores were then transferred into the T scores for comparison to other tasks. The scores of the Purdue Pegboard, Verbal Fluency, TMT, and WCST were also transferred into T scores. Basic General Cognitive Assessment MMSE is a standard tool for cognitive assessment in the clinical setting. The items of the MMSE include tests of

TABLE 1 Demographic Data by Acute and Delayed Carbon Monoxide Poisoning Group Variable

Range

Sex (Male:Female) Age (years) Education (years) COHb (%) Number of HBO treatment MMSE (max ¼ 30) CASI (max ¼ 100) 

p < .05.



p < .01.

28–69 6–16 4.2–54.5 2–18 3–30 3–100

Acute (N ¼ 11) Mean (SD) 7:4 41.71 10.57 31.91 9.67 25.29 86.00

(9.96) (2.50) (12.21) (6.11) (7.09) (15.31)

Delayed (N ¼ 14) Mean (SD) 8:6 44.45 10.91 21.44 4.82 15.64 48.64

(12.93) (3.96) (16.21) (4.05) (8.62) (25.65)

t(1, 23) – 0.47 0.20 1.70 1.75 2.47 3.46

Downloaded by [York University Libraries] at 19:07 10 November 2014

COGNITIVE FUNCTION AND CARBON MONOXIDE POISONING

orientation, memory registration, recall memory, calculation and attention, naming, repetition, comprehension, reading, writing, and drawing (Folstein et al., 1975). The total score is 30, and the mean score for a communitydwelling population older than 65 years of age is 27, with a standard deviation of 1.71 years (Tombaugh & McIntyre, 1992). The MMSE provides a structured approach to mental status testing that screens for intellectual impairment and allows comparison of performance across time and among patients. The Chinese version of the MMSE has a good internal consistency (Cronbach’s alpha ¼ .91; Shyu &Yip, 2001). The CASI, a 25-item test of cognitive function, has a score range of 0 to 100 and provides quantitative assessment on attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, list-generating fluency, abstraction, and judgment. A study of 2,524 elderly participants suggested that a score of 82 or below indicates possible dementia (McCurry et al., 1999). Language Assessment To assess language ability, we employed the subtests of the WAIS-III, including Information and Similarity. The Similarity subtest requires verbal concept formation and abstract reasoning. It is vulnerable to brain conditions that affect verbal functions, so a relatively depressed Similarities score tends to be associated with left temporal and frontal involvement. It is also one of the best indicators of left-hemisphere disease in the WAIS battery (Warrington, James, & Maciejewski, 1986). The Information subtest requires the abilities of verbal comprehension and verbal conduction. During this test, glucose metabolism increases in the left temporal lobe and surrounding areas, with much smaller increases also noted in the right temporal lobe (Chase et al., 1984). Psychomotor Speed/Visual-Spatial Assessment The Purdue Pegboard is a test of manipulative dexterity originally designed for selection in industrial jobs that involve assembling, packing, and operating certain machines (Tiffin & Asher, 1948). In clinical studies, the test has been shown to have great power for discrimination of clumsiness, hyperactivity, and visual-motor dysfunctions (Mack, 1969; Rapin, Tourk, & Costa, 1966). Recently, a brain MRI study showed that psychomotor speed was related to white-matter hyperintensities in an aging community (Sachdev, Wen, Christensen, & Jorm, 2005) and that it also involved the corpus callosum (Marchand, Lefebvre, & Connolly, 2006). Successful performance in the Block Design subtest requires visuoperceptual and analytical skills, intact psychomotor functioning, and spatial reasoning (Caplan

281

& Caffery, 1992). Patients with apraxia (Freedman & Dexter, 1991) have shown poor performance on this task, and a positron emission tomography study has shown a connection to the parietal lobe (Cutler et al., 1985; Narr et al., 2007). Logical Memory Assessment The WMS-III Logical Memory subtest immediate and 30-min delay trials were administered according to the test manual guidelines (Wechsler, 1997). Briefly, Story A and Story B are read once to the examinee, who then orally provides any information recalled. The examiner records the number of free recall units and thematic units, which represent more general information, provided by the examinee. Following 30 min of other testing, the examinee is asked to provide any information recalled from Story A and then Story B. If the examinee has no memory of a story, a standard cue is provided. The recall and thematic unit scores are again recorded. Fifteen yes=no recognition memory questions are then asked about each story, and the recognition memory scores are recorded. Individuals with temporal-lobe epilepsy perform significantly worse compared with the controls on all trials, including immediate recall, retention, and forgetting (Bell, 2006; Lacritz et al., 2004). Working-Memory Assessment The Digit Span and Arithmetic tests in the Wechsler batteries were used as a working-memory index (Conklin, Curtis, Katsanis, & Iacono, 2000; Jahanshahi, Saleem, Ho, Fuller, & Dirnberger, 2008). The Digit Span involves the capacity to maintain information for a short time and reverse the order of the digits. The Arithmetic test requires concentration, attention, low distractibility, contact with reality, mental alertness, numerical reasoning, and speed of numerical manipulation. Past studies have used functional MRI to investigate neural correlates of processes concerning storage and manipulation in working memory. Activated areas specific to maintaining a process have been detected in the right middle frontal gyri and the right inferior parietal lobule (Tsukiura et al., 2001; Vasic et al., 2008). Executive Function Assessment Three tests of executive functioning were administered. The first was the Verbal Fluency Test (Hua, Chang, & Chen, 1997; Tombaugh, Kozak, & Rees, 1999), which includes categories of animals, fruits, and vegetables. For each condition, the score consists of the number of correct responses given within 60 s. The second test was the WCST (Daigneault, Braun, & Whitaker, 1992), which was administered and scored according to the

282

YEH ET AL.

standardized procedures published in the WCST manual (Heaton, 1981). The task involves participants matching cards through trial and error to stimulus cards on the basis of color, shape, or number, and it assesses the ability to identify abstract categories and shift cognitive sets. Studies have shown that patients with lesions in the dorsolateral prefrontal region make significantly more errors and achieve fewer sorting categories on the WCST than do patients with lesions elsewhere in the brain (Rezai et al., 1993). The TMT measures the ability of cognitive flexibility and provides an index of executive function (Arbuthnott & Frank, 2000).

Downloaded by [York University Libraries] at 19:07 10 November 2014

RESULTS Table 2 shows the means and standard deviations of T scores on each neuropsychological test by the acute and delayed CO poisoning groups. The scores were analyzed by a 2  2 (Group  Time) repeated-measures analysis of variance (ANOVA). The results are presented in Table 3. Simple main effects and post-hoc power analysis (Cohen’s d) are reported in Table 4. In the general cognitive index, there was a significant effect on the CASI and MMSE. The simple main effect showed that the scores at 1 month differed significantly between the two groups. Such a difference was also found at 6 months, but only in MMSE scores. A significant difference between the 1st and 6th months was found in the

TABLE 3 The Analysis of Variance (ANOVA) Results for Group and Time on the Neuropsychological Tests ANOVA F(1, 23) Neuropsychological Tests General Cognitive CASI (max ¼ 100) MMSE (max ¼ 30) Language WAIS-Information WAIS-Similarity Psychomotor Speed The Purdue Pegboard (R) The Purdue Pegboard (L) The Purdue Pegboard (B) Visual-Spatial WAIS-Block Design Memory WMS-Logical Memory Working Memory WAIS-Arithmetic WAIS-Digit Span Executive Function Verbal Fluency WCST-Category Trail-Making Test A Trail-Making Test B 

p < .05.



p < .01.



Group

Time

Group  Time

8.09 5.77

18.46 13.90

10.38 3.68

2.48 8.61

9.97 23.20

0.71 1.75

5.74 4.88 4.96

51.65 81.14 43.11

6.49 10.37 4.91

8.36

37.61

14.87

4.47

28.21

2.29

10.13 4.75

17.26 31.17

2.38 4.59

74.01 6.28 3.73 5.78

43.88 16.7 24.33 49.97

2.45 1.81 3.01 2.31

p < .001.

delayed group, but not in the acute group. The effect size also supported such results. The results revealed that the delayed group had lower scores on the CASI and MMSE

TABLE 2 Means and Standard Deviations of Neuropsychological Tests by Acute and Delayed Carbon Monoxide Poisoning Group Acute (N ¼ 11) Mean (SD) Neuropsychological Tests General Cognitive CASI (max ¼ 100) MMSE (max ¼ 30) Language WAIS-Information WAIS-Similarity Psychomotor Speed The Purdue Pegboard (R) The Purdue Pegboard (L) The Purdue Pegboard (B) Visual-Spatial WAIS-Block Design Memory WMS-Logical Memory Working Memory WAIS-Arithmetic WAIS-Digit Span Executive Function Verbal Fluency WCST-Category Trail-Making Test A Trail-Making Test B

Delayed (N ¼ 14) Mean (SD)

First Month

Sixth Month

First Month

Sixth Month

86.00 (15.31) 25.29 (7.09)

90.57 (11.15) 28.29 (3.40)

48.64 (25.65) 15.64 (8.62)

80.64 (17.94) 25.0 (5.06)

49.98 (11.13) 51.74 (10.37)

56.30 (10.08) 58.93 (6.93)

42.53 (7.39) 40.29 (4.37)

53.47 (7.60) 52.92 (8.16)

51.75 (10.51) 50.94 (9.31) 50.21 (10.84)

58.13 (7.83) 57.93 (7.38) 58.24 (4.75)

40.17 (6.26) 37.9 (7.38) 40.09 (7.62)

53.54 (6.27) 54.57 (5.35) 54.53 (5.46)

55.01 (10.87)

57.54 (11.22)

40.45 (3.44)

51.57 (5.58)

50.99 (8.77)

57.81 (7.79)

41.07 (7.18)

53.32 (8.53)

54.95 (9.96) 53.38 (9.83)

58.76 (8.30) 57.28 (9.53)

41.31 (6.27) 42.22 (8.26)

49.97 (7.47) 50.98 (7.51)

50.47 52.95 50.10 49.19

58.12 57.96 57.03 39.77

41.08 41.58 40.50 59.02

53.46 51.48 54.96 54.99

(9.37) (11.40) (12.07) (11.80)

(8.48) (10.02) (3.27) (6.56)

(6.73) (1.96) (9.91) (3.22)

(7.86) (8.78) (3.98) (4.15)

283

COGNITIVE FUNCTION AND CARBON MONOXIDE POISONING TABLE 4 Results of the Simple Main Effect by Group and Time on the Neuropsychological Tests

One Month Between Group Six Months Between Group Acute Group Between Time Delayed Group Between Time

Downloaded by [York University Libraries] at 19:07 10 November 2014

Neuropsychological Tests

t(1, 23)

d

t(1, 23)

d

3.87 2.59

1.56 1.04

1.45 1.65

0.58 0.66

1.43 1.28

0.58 0.52

4.99 4.30

2.01 1.73

1.56 2.77

0.63 1.12

0.64 1.67

0.26 0.67

1.56 2.40

0.63 0.97

3.11 4.73

1.25 1.91

2.63 2.68 2.71

1.06 1.08 1.09

1.31 1.04 1.53

0.53 0.42 0.62

3.37 4.33 2.77

1.36 1.74 1.12

7.33 9.10 7.14

2.95 3.67 2.87

3.44

1.39

1.31

0.53

1.44

0.58

8.08

3.25

2.63

1.06

1.13

0.46

5.07

2.04

4.35

1.75

3.53 2.60

1.02 1.05

2.35 1.57

0.95 0.63

2.16 8.17

0.87 3.29

4.10 4.97

1.65 2.00

2.30 2.62 1.81 1.93

0.93 1.06 0.73 0.78

1.17 1.40 1.19 2.31

0.47 0.56 0.48 0.93

2.50 1.99 1.74 2.52

1.01 0.80 0.70 1.02

General Cognitive CASI (max ¼ 100) MMSE (max ¼ 30) Language WAIS-Information WAIS-Similarity Psychomotor Speed The Purdue Pegboard (R) The Purdue Pegboard (L) The Purdue Pegboard (B) Visual-Spatial WAIS-Block Design Memory WMS-Logical Memory Working Memory WAIS-Arithmetic WAIS-Digit Span Executive Function Verbal Fluency WCST-Category Trail-Making Test A Trail-Making Test B 

p < .05.



p < .01.



t(1, 9)

d

t(1, 12)

8.50 4.08 6.07 10.78

d

3.42 1.64 2.45 4.34

p < .001.

than did the acute group at the 1st month after HBO therapy, and the delayed group also made more progress in the general cognitive domain than did the acute group. The language domain included the Information and Similarity subtests of the WAIS-III. Statistical results showed no significant interaction effect on the Information and Similarity subtests. There was a significant effect on time, and a significant group effect was found on the Similarity subtest, but not on the Information subtest. The simple main effect revealed a significant difference at 1 month between groups on the Similarity subtest, but not on the Information subtest. At 6 months, there were no significant differences between groups on any subtest. The post-hoc results showed that the acute group did not differ in terms of time in the language domain; however, the delayed group showed a difference on these language tasks. Once again, the delayed group showed significantly more progress than did the acute group in this domain. For psychomotor speed, repeated ANOVAs showed significant differences for interaction, time, and group effects on all tests of the Purdue Pegboard: right, left, and both hands. The simple main effect showed that the scores at 1 month differed significantly between the two groups on the right, the left, and both hands, but such differences were not found at 6 months. However, significant differences between 1 month and 6 months were found in the delayed and acute groups. Both groups

demonstrated significant progress in psychomotor speed after HBO therapy, and the delayed group reached almost the same level as the acute group in this cognitive domain. As for visual-spatial ability, repeated ANOVAs also showed significant differences for interaction, time, and group effects on the task of Block Design (WAIS-III). The simple main effect showed that the scores at 1 month differed significantly between the two groups, but this was not the case at 6 months. A significant difference between 1 month and 6 months was found in the delayed group, but not in the acute group. The results revealed that the delayed group had poorer performance compared with the acute group on visual-spatial ability at 1 month after HBO therapy and showed significantly more progress than did the acute group in this domain. Regarding memory and working memory, no interaction was found on the logical memory task, but significant differences were found between time and group. Post-hoc and effect size analysis revealed that delayed groups demonstrated significant progress in the episodic memory domain. The Digit Span and Arithmetic subtests were the working-memory index, and repeated ANOVAs showed that all the effects were significant, except for the interaction effect on the Arithmetic subtest. Post-hoc and effect size analysis revealed that delayed groups had significant progress on the Arithmetic and the Digit Span subtests.

284

YEH ET AL.

Downloaded by [York University Libraries] at 19:07 10 November 2014

TABLE 5 The Difference Scores at 1 Month and 6 Months on the Neuropsychological Tests by Group

General Cognitive CASI (max ¼ 100) MMSE (max ¼ 30) Language WAIS-Information WAIS-Similarity Psychomotor Speed The Purdue Pegboard (R) The Purdue Pegboard (L) The Purdue Pegboard (B) Visual-Spatial WAIS-Block Design Memory WMS-Logical Memory Working Memory WAIS-Arithmetic WAIS-Digit Span Executive Function Verbal Fluency WCST-Category Trail-Making Test A Trail-Making Test B 

p < .05.



Acute (N ¼ 11) Mean (SD)

Delayed (N ¼ 14) Mean (SD)

t (1, 23)

d

6.28 (7.09) 3.86 (5.64)

29.00 (19.50) 8.27 (5.59)

2.93 1.63

1.48 0.97

4.86 (8.24) 6.58 (7.24)

8.41 (8.96) 11.57 (8.11)

0.84 1.32

0.41 0.64

6.03 (5.23) 5.79 (5.68) 7.34 (6.42)

16.21 (7.71) 16.93 (6.83) 16.06 (6.49)

3.06 3.59 2.79

1.50 1.75 1.34

2.12 (3.90)

7.97 (4.39)

2.87

1.40

6.92 (3.61)

12.44 (9.12)

1.51

0.76

0.30 (3.31) 1.80 (4.52)

4.44 (3.59) 7.51 (9.29)

2.45 1.82

1.19 0.75

1.82 1.32 1.73 1.52

0.75 0.65 0.03 0.22

6.10 3.51 1.97 1.23

(8.98) (6.71) (9.22) (7.12)

11.93 8.29 2.26 2.76

(4.66) (7.88) (9.90) (6.97)

Finally, for executive function, only the time effect was significant for Verbal Fluency, WCST-Category, and TMT Parts A and B. Post-hoc analysis indicated that although some scores of the delayed group were lower than those of the acute group at 1 month, almost all reached the same level at 6 months. The delayed group made significant progress between 1 month and 6 months after HBO therapy. For the purpose of comparing the degree of progress between the ANS and DNS groups, the differences in T scores between 1 month and 6 months on each cognitive domain were calculated. The results showed that the DNS group had more significant progress on the CASI, psychomotor speed, visual-spatial ability, and the Arithmetic subtest. Please see Table 5. To rule out the possibility that degree of progress on the cognitive domain could be related to HBO treatment, the scores were reanalyzed using the HBO treatment variable as a covariate, as Table 6 shows. For these analyses of covariance, the group effect for CASI, psychomotor speed, and visual-spatial ability remained significant. Furthermore, when using the COHb level variable as a covariate, the group effect still remained significant for CASI, psychomotor speed, and visual-spatial ability.

p < .01.

DISCUSSION TABLE 6 The Analysis of Covariance (ANCOVA) Results Controlling HBO Treatment and COHb Levels on the Neuropsychological Tests ANCOVA F(1, 22)

Neuropsychological Tests General Cognitive CASI (max ¼ 100) MMSE (max ¼ 30) Language WAIS-Information WAIS-Similarity Psychomotor Speed The Purdue Pegboard (R) The Purdue Pegboard (L) The Purdue Pegboard (B) Visual-Spatial WAIS-Block Design Memory WMS-Logical Memory Working Memory WAIS-Arithmetic WAIS-Digit Span Executive Function Verbal Fluency WCST-Category Trail-Making Test A Trail-Making Test B 

p < .05.



p < .01.

Controlling HBO Treatment

Controlling COHb Levels

5.67 4.10

5.64 4.07

2.13 3.45

2.56 3.74

6.07 10.11 4.92

5.03 7.56 4.32

4.94

4.63

3.67

3.93

4.39 3.17

4.06 3.92

3.01 2.65 2.78 2.11

2.67 1.35 1.76 2.04

Our results indicate that patients with DNS had poorer performance on general cognitive, language, psychomotor speed, visual-spatial, logical and working memory, and executive function compared with those with acute CO poisoning at 1 month, even though their COHb levels were lower than those of the acute group. These results support the first hypothesis, that the DNS group would have poorer performance on psychomotor speed and memory function compared with the ANS group at 1 month after HBO therapy. Moreover, the present study also showed that the DNS group had poorer performance on visual-spatial and executive function than did the ANS group. The results are consistent with previous brain-image research that has shown that patients with DNS had abnormal regions of deep white matter and frontal lobe (Ernst & Zibrak, 1998; Zagami et al., 1993). Few studies have focused on executive function, which reflects the regional function of the prefrontal brain. Executive function is often reduced in patients with CO poisoning, and no studies have investigated the treatment effect on executive function. Some studies have explored the impact of hypoxia on the brain. Obstructive sleep apnea (OSA), a sleep disorder that results in the absence of airflow, may in the long term cause hypoxia in the brain. The results of OSA studies have shown that working memory and executive

Downloaded by [York University Libraries] at 19:07 10 November 2014

COGNITIVE FUNCTION AND CARBON MONOXIDE POISONING

function decline in patients with this disorder and that the prefrontal cortex is responsible for executive dysfunction associated with OSA (Gale & Hopkins, 2004). Therefore, executive function is sensitive to hypoxia in the brain, possibly due to the neuropathology of the prefrontal cortex. Executive function, which includes mental shifting, flexible thinking, and planning, is a higher cognitive function, and it is not generally the focus of medical toxicology concerns. In addition, it is not included in regular examinations of patients with CO poisoning. Because executive function is the basic ability required for maintaining social and occupational functions, and because patients with both ANS and DNS showed great improvement in this ability after HBO therapy, we suggest that executive function be considered an important neuropsychological index. A comprehensive form with good validity for measuring executive function is the Delis-Kaplan Executive Function System (DKEFS), which includes subtests of Trail Making, Verbal Fluency, Design Fluency, ColorWord Interference, Card Sorting, and Proverb Interpretation. The DKEFS is recommended for use in future studies for measurement of executive function (Parmenter et al., 2007; Strong, Tiesma, & Donders, 2011). In the present study, when comparing the degree of progress between the ANS and DNS groups, it is shown that the DNS group had more significant progress on the CASI, psychomotor speed, and visual-spatial ability after controlling numbers of HBO treatment and the COHb levels. The results also supported our second hypothesis. It is seems that COHb level is often used as an indicator of the severity of CO poisoning; however, our findings and other reviews have demonstrated no relationship between COHb level and cognitive performance (Scheinkestel et al., 1999; Thom, Taber, & Mendiguren, 1995). Symptoms of DNS typically develop after an interval of 2 to 240 days, and the pathophysiology of DNS cannot be explained simply by acute hypoxic stress. Notably, the symptoms appear after the COHb level has fallen. Thom et al. (1995) found that patients with CO poisoning with HBO therapy did not develop DNS; however, 23% of patients treated with ambient-pressure 100% oxygen did. Moreover, those patients who were not treated with HBO exhibited a worse mean score on the TMT than did the patients with HBO therapy at a 4-week follow-up assessment (Thom et al., 1995). Some studies have investigated the treatment effect of HBO therapy with indexes of neuropsychological performance. Scheinkestel and colleagues (1999) conducted a double-blind randomized clinical trial to investigate the effects of HBO therapy by measuring performance on neuropsychological tasks immediately after HBO therapy and 1 month later. In response to their findings, Weaver and colleagues (2002) suggested that the neuropsychological tests used in that study should have been standardized and that other cognitive domains should

285

have been included. They also designed a study in which various neuropsychological tests were administrated to patients with CO poisoning after the first session of HBO and at 2 and 6 weeks later. After three sessions of HBO treatment, improvement was found on the neuropsychological tests of Digit Span, Trail Making, Digit-Symbol, Block Design, and Story Recall (Scheinkestel et al., 1999; Weaver et al., 2002). The present study has some limitations. The first is the small sample size. Post-hoc power analysis was performed to compensate for that limitation, and some large effect sizes were also found in the present results. Because previous research provides no neuropsychological data, particularly on memory and executive function, for comparison of acute and delayed CO poisoning groups, the a-priori power analysis is difficult to estimate. However, the present results may provide preliminary neuropsychological data for future research design. Another limitation is the lack of a control group composed of patients with CO poisoning untreated with HBO therapy for comparison. The final limitation is the relatively short time span. Results were collected for only up to 6 months of treatment postinjury. Without the control group, the effectiveness of HBO therapy cannot be measured. However, it would be difficult to recruit an untreated CO poisoning group, because the COHb levels of the patients with CO poisoning in our study (a mean level of 31.91% for the acute group) were significantly higher than the levels in other studies (25% in Weaver et al.’s [2002] study, 20.5% in Scheinkestel et al.’s [1999] study, 20.0% in Thom et al.’s [1995] study. Many studies have suggested that HBO therapy is the recommended treatment for anyone who is symptomatic and has a COHb level of 25% or greater (Stoller & Stoller, 2007); it may cause ethical problem to recruit patients with CO poisoning without HBO or other therapy in the present study. In summary, the present study indicated that patients with DNS had poorer performance on psychomotor speed, memory function, visual-spatial, and executive function than did those with acute CO poisoning at 1 month. Compared with the ANS group, the DNS group had more significant progress at 6-month follow-up on general cognitive function, psychomotor speed, and visual-spatial ability after HBO therapy. In contrast, the follow-up progress on language, logical memory, and executive function tasks did not differ between groups. It is suggested that future studies employ more comprehensive neuropsychological tasks, a large sample size, and matching brain-imaging investigations.

ACKNOWLEDGEMENTS The authors thank all the participants under the care of the Cardinal Tien Hospital. This work was supported by

286

YEH ET AL.

the National Science Council (Grant # NSC 98-2410H-030-014) and the Cardinal Tien Hospital (Grant # CTH-96-2-025).

Downloaded by [York University Libraries] at 19:07 10 November 2014

REFERENCES Amitai, Y., Zlotogorski, Z., Golan-Katzav, V., Wexler, A., & Gross, D. (1998). Neuropsychological impairment from acute low-level exposure to carbon monoxide. Archives of Neurology, 55, 845–848. Arbuthnott, K., & Frank, J. (2000). Trail Making Test, Part B as a measure of executive control: Validation using a set-switching paradigm. Journal of Clinical and Experimental Neuropsychology, 22, 518–528. Bell, B. D. (2006). WMS-III Logical Memory performance after a two-week delay in temporal lobe epilepsy and control groups. Journal of Clinical and Experimental Neuropsychology, 28, 1435–1443. Bryer, J. B., Heck, E. T., & Reams, S. H. (1988). Neuropsychological sequelae of carbon monoxide toxicity at eleven-year follow-up. Clinical Neuropsychologist, 2, 221–227. Caplan, B., & Caffery, D. (1992). Fractionating block design: Development of a test of visuospatial analysis. Neuropsychology, 6, 385–394. Chang, C. C., Chang, W. N., Lui, C. C., Wang, J. J., Chen, C. F., . . . Chen, C. (2010). Longitudinal study of carbon monoxide intoxication by diffusion tensor imaging with neuropsychiatric correlation. Journal of Psychiatry & Neuroscience, 35, 115–125. Chase, T. N., Fedio, P., Foster, N. L., Brooks, R., Di Chiro, G., & Mansi, L. (1984). Wechsler Adult Intelligence Scale performance. Cortical localization by fluorodeoxyglucose F 18-positron emission tomography. Archives of Neurology, 41, 1244–1247. Chen, R. H., & Chen, H. Y. (2002). Wechsler Adult Intelligence Scale III (WAIS-III) of the Chinese version of the instruction manual. Taipei, Taiwan: Chinese Behavior Science Society. Conklin, H. M., Curtis, C. E., Katsanis, J., & Iacono, W. G. (2000). Verbal working memory impairment in schizophrenia patients and their first-degree relatives: Evidence from the digit span task. American Journal of Psychiatry, 157, 275–277. Cutler, N. R., Haxby, J. V., Duara, R., Grady, C. L., Moore, A. M., . . . Rapoport, S. I. (1985). Brain metabolism as measured with positron emission tomography: Serial assessment in a patient with familial Alzheimer’s disease. Neurology, 35, 1556–1561. Daigneault, S., Braun, C. M., & Whitaker, H. A. (1992). Early effects of normal aging on perseverative and non-perseverative prefrontal measures. Developmental Neuropsychology, 8, 99–114. Ernst, A., & Zibrak, J. D. (1998). Carbon monoxide poisoning. The New England Journal of Medicine, 339, 1603–1608. Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). Mini-Mental State: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198. Freedman, L., & Dexter, L. E. (1991). Visuospatial ability in cortical dementia. Journal of Clinical and Experimental Neuropsychology, 13, 677–690. Gale, S. D., & Hopkins, R. O. (2004). Effects of hypoxia on the brain: Neuroimaging and neuropsychological findings following carbon monoxide poisoning and obstructive sleep apnea. Journal of the International Neuropsychological Society, 10, 60–71. Gale, S. D., Hopkins, R. O., Weaver, L. K., Bigler, E. D., Booth, E. J., & Blatter, D. D. (1999). MRI, quantitative MRI, SPECT and neuropsychological findings following carbon monoxide poisoning. Brain Injury, 13, 229–243. Goldstein, M., & Goldstein, M. (2008). Carbon monoxide poisoning. Journal of Emergency Nursing, 34, 538–542. Grattan, L., Eslinger, P. J., & Faust, D. (1988). Case report: Reversible neuropsychological impairment after severe carbon monoxide poisoning in a child. Developmental Neuropsychology, 4, 37–46.

Heaton, R. K. (1981). A manual for the Wisconsin Card Sorting Test. Odessa, FL: Psychological Assessment Resources. Heinrichs, R. (1990). Relationship between neuropsychological data and response to behavioral treatment in a case of carbon monoxide toxicity and dementia. Brain and Cognition, 14, 213–219. Hopkins, R. O., & Weaver, L. K. (1995). Carbon monoxide controversies: Neuropsychologic testing, mechanism of toxicity, and hyperbaric oxygen. Annals of Emergency Medicine, 25, 272–273. Hua, M. S., Chang, B. S., Lin, K. N., Yung, C. M., & Chen, H. Y. (2005). Wechsler Memory Scale III (WMS-III) Chinese version of the instruction manual. Taipei, Taiwan: Chinese Behavior Science Society. Hua, M. S., Chang, S. H., & Chen, S. T. (1997). Factor structure and age effects with an aphasia test battery in normal Taiwanese adults. Neuropsychology, 11, 156–162. Jahanshahi, M., Saleem, T., Ho, A. K., Fuller, R., & Dirnberger, G. (2008). A preliminary investigation of the running digit span as a test of working memory. Behavioural Neurology, 20, 17–25. Lacritz, L. H., Barnard, H. D., Van Ness, P., Agostini, M., Diaz-Arrastia, R., & Cullum, C. M. (2004). Qualitative analysis of WMS-III Logical Memory and Visual Reproduction in temporal lobe epilepsy. Journal of Clinical & Experimental Neuropsychology, 26, 521–530. Mack, J. L. (1969). Validity of the Purdue Pegboard as a screening test for brain damage in a psychiatric population. Perceptual and Motor Skills, 28, 832–834. Marchand, Y., Lefebvre, C. D., & Connolly, J. F. (2006). Correlating digit span performance and event-related potentials to assess working memory. International Journal of Psychophysiology, 62, 280–289. McCurry, S. M., Edland, S. D., Teri, L., Kukull, W. A., Bowen, J. D., McCormick, W. C., & Larson, E. B. (1999). The Cognitive Abilities Screening Instrument (CASI): Data from a cohort of 2524 cognitively intact elderly. International Journal of Geriatric Psychiatry, 14, 882–888. Min, S. K. (1986). A brain syndrome associated with delayed neuropsychiatric sequelae following acute carbon monoxide intoxication. Acta Psychiatrica Scandinavica, 73, 80–86. Narr, K. L., Woods, R. P., Thompson, P. M., Szeszko, P., Robinson, D., . . . Bilder, R. M. (2007). Relationships between IQ and regional cortical gray matter thickness in healthy adults. Cerebral Cortex, 17, 2163–2171. Parmenter, B. A., Zivadinov, R., Kerenyi, L., Gavett, R., WeinstockGuttman, B., Dwyer, M. G., . . . Benedict, R. H. (2007). Validity of the Wisconsin Card Sorting and Delis-Kaplan Executive Function System (DKEFS) Sorting Tests in multiple sclerosis. Journal of Clinical & Experimental Neuropsychology, 29, 215–223. Pepe, G., Castelli, M., Nazerian, P., Vanni, S., Del Panta, M., . . . Grifoni, S. (2011). Delayed neuropsychological sequelae after carbon monoxide poisoning: Predictive risk factors in the Emergency Department. A retrospective study. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 19(16), 18. Rapin, I., Tourk, L. M., & Costa, L. D. (1966). Evaluation of the Purdue Pegboard as a screening test for brain damage. Developmental Medicine & Child Neurology, 8, 45–54. Rezai, K., Andreasen, N. C., Alliger, R., Cohen, G., Swayze, I. V., & O’Leary, D. S. (1993). The neuropsychology of the prefrontal cortex. Archives of Neurology, 50, 636–642. Sachdev, P. S., Wen, W., Christensen, H., & Jorm, A. F. (2005). White matter hyperintensities are related to physical disability and poor motor function. Journal of Neurology, Neurosurgery & Psychiatry, 76, 362–367. Scheinkestel, C. D., Bailey, M., Myles, P. S., Jones, K., Cooper, D. J., Millar, I. L., & Tuxen, D. V. (1999). Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: A randomised controlled clinical trial. Medical Journal of Australia, 170, 203–210.

Downloaded by [York University Libraries] at 19:07 10 November 2014

COGNITIVE FUNCTION AND CARBON MONOXIDE POISONING Shyu, Y. I., & Yip, P. K. (2001). Factor structure and explanatory variables of the Mini-Mental State Examination (MMSE) for elderly persons in Taiwan. Journal of the Formosan Medical Association, 100, 676–683. Sohn, Y. H., Jeong, Y., Kim, H. S., Im, J. H., & Kim, J. S. (2000). The brain lesion responsible for Parkinsonism after carbon monoxide poisoning. Archives of Neurology, 57, 1214–1218. Stoller, K. P., & Stoller, K. P. (2007). Hyperbaric oxygen and carbon monoxide poisoning: A critical review. Neurological Research, 29, 146–155. Strong, C. A., Tiesma, D., & Donders, J. (2011). Criterion validity of the Delis-Kaplan Executive Function System (D-KEFS) fluency subtests after traumatic brain injury. Journal of the International Neuropsychological Society, 17, 230–237. Thom, S. R., Taber, R. L., & Mendiguren, I. I. (1995). Delayed neuropsychologic sequelae after carbon monoxide poisoning prevention by treatment with hyperbaric oxygen. Annals of Emergency Medicine, 25, 474–480. Tiffin, J., & Asher, E. (1948). The Purdue Pegboard: Norms and studies of reliability and validity. Journal of Applied Psychology, 32, 234–247. Tombaugh, T. N., Kozak, J., & Rees, L. (1999). Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming. Archives of Clinical Neuropsychology, 14, 167–177.

287

Tombaugh, T. N., & McIntyre, N. J. (1992). The Mini-Mental State Examination: A comprehensive review. Journal of the American Geriatrics Society, 40, 922–935. Tsukiura, T., Fujii, T., Takahashi, T., Xiao, R., Inase, M., . . . Okuda, J. (2001). Neuroanatomical discrimination between manipulating and maintaining processes involved in verbal working memory; a functional MRI study. Cognitive Brain Research, 11, 13–21. Vasic, N., Lohr, C., Steinbrink, C., Martin, C., & Wolf, R. C. (2008). Neural correlates of working memory performance in adolescents and young adults with dyslexia. Neuropsychologia, 46, 640–648. Vicente, P. J. (1980). Neuropsychological assessment and management of a carbon monoxide intoxication patient with consequent sleep apnea: A longitudinal case report. Clinical Neuropsychology, 2, 91–94. Warrington, E. K., James, M., & Maciejewski, C. (1986). The WAIS as a lateralizing and localizing diagnostic instrument: A study of 656 patients with unilateral cerebral lesions. Neuropsychologia, 24, 223–239. Weaver, L. K., Hopkins, R. O., Chan, K. J., Churchill, S., Elliott, C. G., . . . Morris, A. H. (2002). Hyperbaric oxygen for acute carbon monoxide poisoning. The New England Journal of Medicine, 347, 1057–1067. Wechsler, D. (1997). Manual for the Wechsler Memory Scale-Third Edition. San Antonio, TX: The Psychological Corporation. Zagami, A. S., Lethlean, A. K., & Mellick, R. (1993). Delayed neurological deterioration following carbon monoxide poisoning: MRI findings. Journal of Neurology, 240, 113–116.