Chapter 10. Long-term cognitive outcome after decompressive surgery for space-occupying hemispheric infarction

Transcription

1 Cognitive outcome after decompressive surgery Chapter 10 Long-term cognitive outcome after decompressive surgery for space-occupying hemispheric infarction Jeannette Hofmeijer, H. Bart van der Worp, G. Johan Amelink, L. Jaap Kappelle, Gudrun M.S. Nys, and Martine J.E. van Zandvoort In preperation 133

2 Chapter 10 Summary In patients with space-occupying hemispheric infarction, decompressive surgery may reduce mortality without increasing the number of severely disabled survivors. However, cognitive functioning in surviving patients has been largely neglected. Ten consecutive patients with a space-occupying hemispheric infarction, who had been included in the surgical arm of the randomized Hemicraniectomy After spaceoccupying Middle cerebral artery (MCA) infarction with Life-threatening Edema Trial (HAMLET) underwent neuropsychological testing approximately one year after decompressive surgery. The tests comprised the following cognitive domains: general cognitive functioning, language, memory, visual perception, neglect, and executive functioning. Testing of general cognitive functioning was severely hampered in all five patients with infarcts in the dominant hemisphere, and in three of the five patients with infarcts in the non-dominant hemisphere cognitive functioning was severely impaired. Testing of language or verbal memory was not feasible or disclosed severe impairments in patients with infarction in the dominant hemisphere. Non-verbal memory was impaired in all patients with infarction in the non-dominant hemisphere and in three of the patients with infarction in the dominant hemisphere. Visual perception was impaired in four patients and below average in two. All patients with infarction in the non-dominant hemisphere suffered profound hemispatial neglect. Executive functioning was below average or impaired in all patients. In general, patients with infarction in the non-dominant hemisphere performed better than patients with infarction in the dominant hemisphere. In addition to the expected severe focal deficits, such as aphasia and neglect, global cognitive decline was found in the majority of patients. Cognitive functioning in patients with infarction in the dominant hemisphere was worse than in patients with infarction in the non-dominant hemisphere. Before implementing decompressive surgery as standard treatment in patients with space-occupying hemispheric infarction, results of cognitive assessments of patients included in ongoing trials should be awaited. 134

3 Cognitive outcome after decompressive surgery Large cerebral infarcts may cause space-occupying edema that puts the patient at risk of transtentorial or uncal herniation. 1 Fatal space-occupying brain edema occurs in 1-5% of patients with a supratentorial infarct. 2,3 The case fatality rate of space-occupying infarcts has been reported to be as high as 78%, despite maximal medical therapy on an intensive care unit. 1,4 The aim of decompressive surgery in patients with space-occupying hemispheric infarction is to revert brain tissue shifts and to normalize intracranial pressure, thereby presumably preserving cerebral blood flow and preventing secondary damage. 5 Case reports and non-randomized patient series have suggested a substantial reduction in mortality after decompressive surgery without an increase in the number of severely disabled survivors For assessment of functional outcome, most investigators used the modified Rankin Scale (mrs) and defined favorable outcome as a score of 4 or lower, representing moderately severe disability at best. 11 Reports on cognitive outcome after decompressive surgery are scarce. The only study so far reports on 14 patients subjected to decompressive surgery for space-occupying infarction, however, this study selectively included patients with right-sided infarction and a relatively mild handicap. 12 Over the last few years, cognitive functioning has become an important outcome measure in stroke research, as this has shown to be crucial to dependence in daily life, 13,14 long-term survival, 15 and more subjective measures such as quality of life. 16 To study long-term cognitive impairments in unselected patients after decompressive surgery for space-occupying hemispheric infarction, we performed comprehensive neuropsychological testing one year after surgery. Methods Patients Between September 2003 and November 2006, all consecutive patients with a spaceoccupying hemispheric infarct who had been included in the surgical arm of the Hemicraniectomy After space-occupying Middle cerebral artery (MCA) infarction with Life-threatening Edema Trial (HAMLET) underwent neuropsychological testing approximately one year after surgery. Patients were included in HAMLET if the following inclusion criteria had been met: 17 (1) age 18 up to and including 60 years, (2) clinical deficits consistent with infarction in the territory of the middle cerebral artery with a score on the National Institutes of Health Stroke Scale (NIHSS) > 15, 18 (3) decrease in consciousness to a score of 13 or lower on the Glasgow Coma Scale for patients without aphasia, or an Eye and Motor score of 9 or lower for patients with aphasia, (4) signs on CT or MRI of a unilateral infarct in at least 50% of the territory of the MCA, with or without additional infarction of the territories of the anterior (ACA) or posterior cerebral artery (PCA) on the same side, (5) inclusion within 96 hours 135

4 Chapter 10 after the onset of symptoms, and (6) written informed consent by the patient or a legal representative. Exclusion criteria were: (1) pre-stroke mrs 11 2, (2) presence of two fixed dilated pupils, (3) contralateral ischemia or other serious brain lesions, (4) spaceoccupying hemorrhagic transformation of the infarct, defined as PH2 according to ECASS criteria, 19 (5) life expectancy <3 years, (6) other serious illness that may affect outcome, (7) known coagulopathy or systemic bleeding disorder, (8) contra-indication for anesthesia, and (9) pregnancy. Data collection Demographic data were collected at the time of admission. Stroke severity was assessed on admission and before surgical treatment. Infarct side and location were assessed on CT scans made at randomization and follow-up. Neuropsychological examination was performed at the University Medical Center Utrecht approximately one year after surgery. The duration of the test procedure was dependent on the patient s performance and varied between one and two hours. The neuropsychological examination comprised (1) a standardized battery for general cognitive functioning [Cambridge Cognitive Examination (CAMCOG)] 20 and nine tasks tapping the following cognitive domains: (2) language [Boston Naming Task, Token Task (21-item short form), Category Fluency (animals)], (3) memory [Rey Auditory Verbal Learning Task (verbal), Location Learning Task (non-verbal)], (4) visual perception [Judgment of Line Orientation], (5) neglect [Star Cancellation], and (6) executive functioning [Ruff Figural Fluency Test and Letter Fluency (N,A)]. This test battery was developed for screening all major cognitive domains, but without being too extensive, given the expected severe cognitive deficits. Memory and Executive functioning were assessed in both a verbal and a non-verbal way in order to overcome possible feasibility problems with either language (dominant hemisphere dysfunctioning) or non-verbal visuospatial information (non-dominant hemisphere dysfunctioning). Outcome measures and analysis Data are presented in a qualitative way, using the population norms of the neuropsychological tests, corrected for age and level of education. 20 Either test-specific cut-off values were used to describe the level of functioning (CAMCOG, Token Task), or the raw scores were converted into percentiles of the general population, to adjudge a level of functioning ranging from impaired (< -2 standard deviations (SD)), below average ( -2SD and < -1SD), average ( -1SD and 1SD), high average (> 1SD and 2SD), or superior (> 2SD). To compare performance of patients with infarcts in the dominant and the non-dominant hemisphere, the number of test scores above the level of impaired was calculated. The Mann Whitney U test was used to test differences between the groups. P < 0.05 was considered statistically significant. 136

5 Cognitive outcome after decompressive surgery Table 1 Baseline data. Patient number Sex Age (years) Infarct side Infarct location NIHSS at randomization mrs 1 year 1 F 49 Left MCA M 50 Left MCA+ACA F 59 Left MCA+PCA M 38 Left MCA+PCA M 57 Right MCA+ACA M 57 Right MCA M 54 Right MCA F 44 Right MCA+ACA M 59 Right MCA F 44 Right MCA 23 4 F indicates female; M, male; MCA, middle cerebral artery; ACA, anterior cerebral artery; PCA, posterior cerebral artery; NIHSS, National Institutes of Health Stroke Scale; mrs, modified Rankin Scale. Results As of December 1 st, 2006 twelve patients had been eligible for neuropsychological examination one year after hemicraniectomy. Two patients refused to participate, because of fear to be confronted with cognitive decline. The mean interval ± SD between stroke onset and testing was 14.4 ± 1.6 months. Baseline data are summarized in Table 1. Patient number 9 had an infarct in the right hemisphere with aphasia. This patient was left-handed. One patient had an mrs score of 5, indicating severe disability, eight patients had an mrs score of 4, indicating moderately severe disability and one patient was functionally independent but needed help with some daily activities (mrs score of 3). Hetero-anamnestic information from patients relatives disclosed that, in general, patients were cognitively impaired. Relatives often mentioned inability to plan and structure activities interfering with daily life functioning, and problems with impulse regulation. Moreover, the capacity to adapt to new situations was often impaired, leading to frequent frustrations. Test performances are summarized in Table 2. Testing of general cognitive functioning was severely hampered in the four patients with left hemisphere infarction and in one patient with right hemisphere infarction as a result of language impairments. These five patients met the criteria for global aphasia (severe impairment in both comprehension and production of language) prohibiting verbal communication. General cognitive functioning was impaired in three of the five patients with infarcts in the dominant hemisphere. Verbal memory was not testable in patients with infarcts in the dominant 137

6 Chapter 10 Table 2 Neuropsychological test performance. Patient number CAMCOG Boston Naming Task Token Task Category Fluency Rey Auditory Verbal Learning Rey Auditory Verbal Learning del Location Learning Task displ Location Learning Task learn Location Learning Task del Judgment of Line Orientation Star Cancellation Figural Fluency Number of tasks above impaired 1 na na na na na na avg avg na imp avg imp 3 2 na imp imp na na na imp imp imp avg avg bavg 3 3 na na imp na na na avg bavg avg bavg avg na 5 4 na na na na na na na na na na na na 0 5 avg sup sup avg avg nvg imp imp avg avg negl imp 8 6 imp imp imp na bavg navg imp imp imp imp negl imp 2 7 avg avg avg avg bavg navg imp imp havg imp negl imp 7 8 imp avg avg avg bavg nvg imp imp avg imp negl imp 6 9 na imp imp na na na imp bavg bavg avg avg imp 4 10 imp avg avg imp avg navg bavg imp havg bavg negl imp 7 na indicates not assessable; del, delayed recall; displ, displacement score; learn, learning index; imp, impaired; bavg, below average; avg, average; havg, high average; sup, superior; negl, neglect. Figure Cognitive functioning defined as the number of test-scores above the level of impaired for patients with infarcts in the dominant and the non-dominant hemisphere. Box plots indicate Medians, Quartiles, and Ranges. 138

7 Cognitive outcome after decompressive surgery hemisphere, and below average in four of the five patients with infarcts in the nondominant hemisphere. Non-verbal memory was impaired in all patients with infarcts in the non-dominant hemisphere and in three of the patients with infarcts in the dominant hemisphere. Visual perception was impaired in four patients and below average in two. All patients with infarcts in the non-dominant hemisphere suffered severe hemispatial neglect. Executive functioning was below average or impaired in all patients. In general, patients with infarcts in the non-dominant hemisphere tended to perform better than patients with infarcts in the dominant hemisphere (Figure), but this difference did not reach statistical significance (P = 0.08). Discussion This is the first report of neuropsychological examination in unselected patients after decompressive surgery for space-occupying MCA infarction. Cognitive functioning was poor in the majority. In addition to the expected severe focal deficits, such as aphasia and neglect, executive functioning and memory were affected in all patients resulting in below average or impaired performance. Several studies have shown a decline in cognitive functioning after all types of stroke. 21,22 Higher cognitive functions are not solely located in a specific area of the brain, but are the result of complex and dynamic neural networks which are scattered throughout the brain. 23 For this reason, neuropsychological functioning is highly dependent on the overall integrity of the brain, and may be impaired even after lacunar or brainstem infarction, 24,25 let alone after large cortical infarcts. Irrespective of the side of infarction, most patients had a score on the mrs of 4. Nevertheless, patients with infarction in the dominant hemisphere performed worse than patients with infarcts in the non-dominant hemisphere, having impairments on both verbal and non-verbal tasks. Similar findings have been reported earlier in a more general stroke population. 22 Language probably has a far-reaching impact on cognitive functioning and should be considered as the means by which most cognitive functions are articulated. 21 Executive functioning, as tested with the Ruff Figural Fluency Test, was below average or impaired in all patients. This cannot be completely attributed to the presence of aphasia, amnesia, or a reduction in motor speed. The impaired performance reflects an inflexibility in information processing and an impairment in generation of ideas. In daily life this means that patients may become locked into one strategy and do not possess the ability to change to another. Relatives of patients with lesions in the non-dominant as well as relatives of patients with lesions in the dominant hemisphere have confirmed this observation. According to their relatives, the patients inability to initiate, plan and structure activities interferes with daily life functioning. Moreover, the capacity to adapt to new situations appears to be impaired to such an amount that 139

8 Chapter 10 this leads to frequent frustrations. Next to executive functioning, both verbal and non-verbal memory were impaired in most patients. Memory and the ability to learn probably deteriorate even more by disturbances of attention and concentration. In a previous study of cognitive functioning in patients with large MCA infarction subjected to decompressive surgery, profound disturbances of attention were found. In this study only patients with rightsided infarction and with a relatively preserved level of functioning were included. 12 We performed neuropsychological examination more than one year after the onset of symptoms. Although further cognitive recovery after the first year following stroke has been described, 26 a lack of improvement or even cognitive decline in the second year after stroke onset has also been reported. 27 Patients with aphasia not only tend to perform worse, but also show less improvement. 27,28 Thus, in our patients further improvement is probably very limited. The current study has limitations. First, the small sample size precludes definitive conclusions on the effects of cognitive and functional outcome. Despite the overall low performance, two patients (patient 5 and 7) performed average or above average on most tasks. Neuropsychological evaluation of all patients participating in randomized trials of decompressive surgery in space-occupying infarction is clearly warranted. Secondly, because of the small sample size, data were mainly presented in a descriptive way. Nevertheless, the serious impact of life-threatening space-occupying infarction on cognition is evident. Thirdly, in patients with infarcts in the dominant hemisphere language was too poor to be quantified by means of any of the tasks included in the test battery. In general, neuropsychological examination is feasible in the majority of patients with aphasia caused by stroke. 14 Although floor effects prevented quantification in our series, these may still be seen as an indication of the magnitude of the damage in these patients. Finally, the present study did not include a control group of patients with space-occupying MCA infarcts that did not undergo surgery. For this reason, we do not know the impact of decompressive surgery on cognition in this patient population. In conclusion, although decompressive surgery increased the probability of a favorable outcome in patients with space-occupying MCA infarction in a pooled analysis of ongoing trials (chapter 11), the present results suggest that survivors are likely to be left with significant cognitive impairments. Despite similar functional dependence as assessed with the mrs, cognitive functioning in patients with infarction in the dominant hemisphere was worse than in patients with infarction in the non-dominant hemisphere. Before implementing decompressive surgery as a standard treatment modality in patients with MCA infarction, who deteriorate as a result of space-occupying edema, results of cognitive assessments of patients included in ongoing trials should be awaited. Moreover, the possible cognitive consequences, especially for patients with a stroke in the dominant hemisphere, should be considered before a decision to perform surgery is taken. 140

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