- Email: [email protected]
Splenium or parahippocampus involvement and its relationship to cognitive decline in posterior cerebral artery infarction
Journal of Clinical Neuroscience 16 (2009) 914–917
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Splenium or parahippocampus involvement and its relationship to cognitive decline in posterior cerebral artery infarction Key-Chung Park a,*, Sung-Sang Yoon a, Kyung-Hwa Seo b a b
Department of Neurology, Kyung Hee University, School of Medicine, 1 Hoegi-dong, Dongdaemoon-ku, Seoul, 130-702, Korea Department of Management, Kyung Hee University, Graduate College, Seoul, Korea
a r t i c l e
i n f o
Article history: Received 17 February 2008 Accepted 16 September 2008
Keywords: Cognitive decline MMSE Parahippocampus Posterior cerebral artery infarction Splenium
a b s t r a c t Although cognitive impairment after a posterior cerebral artery (PCA) infarct is frequently observed, the important functional areas associated with cognitive decline, other than the thalamus, have not been determined. We investigated the locus or loci that might induce cognitive decline after a PCA infarct. Forty-one patients with unilateral PCA infarctions involving only the occipital lobe or the occipital lobe plus other PCA areas were included. All subjects received a mini-mental status examination (MMSE) within 2 months of onset; 43.9% had cognitive impairment. The severity of cognitive impairment was not associated with left hemisphere lesion location, sex, age, education level, or the time between stroke and the MMSE assessment. Only the lesion volume was negatively correlated with MMSE score. Lesion location analysis revealed that an occipital plus splenial or parahippocampal lesion contributed to a decline in MMSE, which suggests that parahippocampal or splenial involvement with an occipital lesion is associated with the cognitive decline seen after PCA infarction. Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction Posterior cerebral artery (PCA) territory infarcts account for 5% to 10% of all strokes.1 Cognitive impairment after PCA infarcts is observed frequently and diverse neuropsychological deficits including dysphasia, amnesia, pure alexia, dyscalculia, visual neglect, and visual agnosia are described.1–5 A lesion localization study showed that vascular dementia was associated with PCA infarction of the paramedian thalamic or inferior medial temporal areas, and with lesions of the parieto-temporal or temporo-occipital territories.6 However, apart from the thalamus, other strategic areas within the PCA territory associated with cognitive decline have not been investigated.7,8 The development of MRI has allowed improved localization of lesion topography. The areas frequently involved in PCA infarcts are the occipital lobe, posterior ventral temporal lobe (fusiform and parahippocampal gyrus), thalamus, corpus callosum splenium, posterior cingulate gyrus, and retrosplenial cortex.1,9 We aimed to determine the locus or loci that might be involved in cognitive impairments after PCA infarction. We performed a lesion localization study in patients with PCA territory infarcts using
* Corresponding author. Tel.: +82 2 958 8447; fax: +82 2 958 8490. E-mail address: [email protected] (K.-C. Park). 0967-5868/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2008.09.010
mini-mental status examination (MMSE).10 The advantages of a MMSE are that it requires only 5 min to 10 min to evaluate the patient’s global cognitive state, and that the test is highly reliable between individual scorers and between tests.11
2. Methods 2.1. Patients The study included 41 patients (26 men and 15 women) with unilateral PCA infarctions involving the cerebral cortex. The mean age (±standard deviation [SD]) was 61.59 ± 14.15 years (range: 29– 87 years) with a mean (±SD) of 9.24 ± 4.32 years of education (range: 0–16 years). From April 2003 to September 2003, subjects were recruited consecutively from acute stroke units of four general hospitals in Seoul, Korea. Inclusion criteria were right-hand preference as assessed by Edinburgh Handedness Inventory,12 stroke onset less than 60 days prior, alertness, and cooperation. Exclusion criteria were prior stroke, aphasia severe enough to interfere with test taking, and a history of cognitive impairment. A complete neurological examination was performed and a neurologist, who was blinded to lesion location, assessed the MMSE. Cognitive impairment was defined as a score below 24 points on the MMSE. This study was performed in accordance with the ethical standards of the Declaration of Helsinki. All subjects provided informed consent.
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K.-C. Park et al. / Journal of Clinical Neuroscience 16 (2009) 914–917
2.2. Lesion analysis In each scan section, the lesion boundary on CT scan (2/41) or T2-weighted MRI (39/41) was visually identified and outlined using a manual pixelwise method with the aid of a picture archiving and communication system (PACS) workstation (General Electric Medical Systems, Cincinatti, OH, USA). Lesion volume (in cm3) was calculated by multiplying the area of lesions in consecutive CT scan slices by the slice thickness, and in consecutive MRI slices by the slice thickness plus the interslice gap distance. A neurologist blinded to the patient’s clinical status measured the lesion volume.13 To define lesion location, two neurologists, unaware of clinical findings, coded the involved lesion as the occipital lobe, temporal fusiform gyrus, parahippocampal gyrus, corpus callosum splenium, thalamus, or posterior cingulate gyrus. 2.3. Statistical analysis We used an independent t-test and multiple linear regression models to investigate the relationship between sex, PCA lesion side and volume, age, years of education, time of stroke onset to MMSE test, severity of cognitive impairment (as indicated by continuous MMSE scores), and the presence of a lesion following infarction. To assess the relationship between lesion location and cognitive impairment (as categorized MMSE scores), we performed multiple
logistic regression. All statistical analyses were conducted using the Statistical Package for the Social Sciences version 13.0 (SPSS; Chicago, IL, USA). P < 0.05 was set as a two-tailed statistical significance level. 3. Results 3.1. Variables affecting MMSE score The mean time interval (±SD) between onset of infarction and brain imaging was 3.71 ± 3.23 days. Mean time (±SD) from onset of infarction to the MMSE test was 13.90 ± 14.84 days. The mean MMSE score was 22.98 ± 6.01. Twenty-four patients had right PCA infarction and 17 had left involvement. Motor power was normal in all patients, except for two patients with mild hemiparesis, which was above grade 4 on the Medical Research Council Scale for motor testing. Eighteen (43.9%) had cognitive impairment, defined as a MMSE score below 24 points. Cognitive decline after left and right PCA infarction occurred in 11 of 24 (45.8%) and 7 of 17 (41.2%) patients, respectively. Cognitive impairment severity (MMSE score) did not differ between right and left PCA infarctions (mean ± SD; right: 22.75 ± 6.22, left: 23.29 ± 5.87, t = 0.28, p = 0.779) or by sex (t = 1.46, p = 0.153). Impairment did not appear to be influenced by the interval between stroke onset and MMSE assessment (t = 1.85, p = 0.072), age (t = –0.93, p = 0.358), or level of education
Table 1 Demographics and clinical features of patients with PCA infarction (n = 41) Case Sex/age (years)
Onset (days)
Hemisphere
MMSE (total)
Stroke location
CT scan or MRI
Lesion volume (cm3)
1. M/58 2. M/73 3. F/35 4. M/70 5. M/36 6. M/30 7. F/29 8. M/67 9. M/54 10. M/70 11. M/71 12. M/64 13. F/38 14. M/57 15. F/61 16. F/56 17. M/53 18. M/44 19. M/49 20. M/87 21. M/45 22. F/69 23. M/63 24. M/69 25. M/59 26. M/70 27. M/73 28. F/57 29. F/80 30. F/68 31. M/73 32. F/70 33. F/69 34. M/54 35. F/68 36. M/65 37. F/71 38. M/83 39. M/77 40. F/66 41. F/75
4 7 4 59 49 19 17 29 9 16 12 3 1 8 8 1 5 1 20 6 3 6 59 33 20 21 16 26 4 7 34 5 1 11 4 8 3 1 6 8 16
Left Left Left Left Left Left Left Left Left Left Left Left Left Left Left Left Left Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right
25 17 29 27 29 25 30 25 27 28 24 29 15 9 18 19 19 27 27 25 29 27 30 27 25 24 26 27 15 24 13 17 27 24 24 30 14 25 7 17 15
O, O O O, O O, O, O, O, O, O, O O, O, O, O, O, O O, O, O O O, O O O, O, O O, O, O, O, O, O, O, O, O, O, O, O, O,
MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI CT MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI CT
57.61 3.86 5.34 26.07 11.29 22.28 39.25 15.68 60.60 26.45 5.07 9.02 46.74 9.68 70.56 21.96 16.54 7.14 17.50 15.97 15.18 32.80 36.74 31.35 21.26 46.89 40.23 41.91 38.49 48.43 68.10 99.34 26.47 45.92 22.48 33.07 41.06 1.63 68.89 61.34 17.94
Fu, PH, Th
Spl Spl, Th CG Spl Fu, PH, Spl, Th Fu, PH Fu, PH, Spl Fu, PH, Spl, Th, CG Spl, Th, MB PH Fu, PH, Th, MB PH, Spl Spl CBLL
Fu, PH
PH, Spl Fu, PH PH, Th, CBLL Spl, CG, CBLL Fu, PH, Spl, Th Fu, PH, Spl, Th Fu Fu, PH, Spl, Th Fu, PH, Spl, Th Spl Fu, PH, Th CBLL Fu, PH, Spl, CG Fu, PH Fu, SplC)
CBLL = cerebellum, CG = cingulate gyrus, F = female, Fu = fusiform gyrus of temporal lobe, M = male, MB = midbrain, MMSE = Mini-mental status examination, O = occipital lobe, Onset = time from stroke onset to MMSE test, PH = parahippocampal gyrus, Spl = splenium, Th = thalamus.
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Table 2 The relationship between mini-mental status examination score and lesion locus Lesion locus Fusiform gyrus Parahippocampal gyrus Splenium Thalamus Cingulate gyrus
Crude odds ratio
p-value *
Adj. OR ,§
p-value
4.45 (1.18–16.81) 12.60 (2.84–55.84)
0.028 0.001**
4.40 (0.53–36.45) 99.92 (3.02–3303.68)
0.169 0.010*
5.67 (1.47–21.89) 6.67 (1.45–60.64) 4.40 (0.42–46.43)
0.012* 0.015* 0.218
133.84 (2.83–6320.86) 6.88 (0.77–61.22) 1.65 (0.06–49.31)
0.013* 0.084 0.774
*
p-value < 0.05. p-value < 0.01. Adjusted for sex, side of PCA lesion, age, duration of education, lesion volume, interval time from stroke onset to test assessment. PCA = posterior cerebral artery. 95% confidence intervals shown in brackets. ** §
(t = 1.67, p = 0.104). In contrast, only lesion volume showed a negative correlation with MMSE (t = –2.20, p = 0.035). 3.2. MMSE score and lesion loci relationship Lesion location analysis showed that the occipital lobe was affected in all patients. Of the 12 patients with lesions confined to the occipital lobe, only one had cognitive decline. The other lesion sites, in order of decreasing frequency, were the parahippocampal gyrus (19/41, 46.3%), corpus callosum splenium (18/41, 43.9%), temporal fusiform gyrus (17/41, 41.5%), thalamus (12/41, 29.3%), and posterior cingulate gyrus (4/41, 9.8%) (Table 1). Using multiple logistic regression analysis, we investigated the relationship between the loci of the injured area and cognitive impairment. No multi-colinearity existed between lesions and controlled variables. For regression analysis, sex, PCA lesion side, age, lesion volume, education duration, and period from stroke onset to assessment were adjusted. All candidate lesions (fusiform gyrus, parahippocampal gyrus, splenium, thalamus, and posterior cingulate gyrus) were used in a multiple logistic regression model with MMSE scores. Analysis revealed that the splenium and parahippocampal gyrus were associated with cognitive impairment when other factors affecting MMSE scores were adjusted (splenium: adjusted odds ratio = 133.84, CI 2.83–6320.86, p = 0.013; parahippocampal gyrus: adjusted odds ratio = 99.92, CI 3.02–3303.68, p = 0.010) (Table 2). 4. Discussion In our study, the frequency of cognitive decline after a first episode of acute occipital or occipital plus other region infarctions in the PCA territory was 43.9%. Cognitive impairment was influenced by larger lesion volume and was not influenced by age, sex, lesion location (left versus right), level of education, or interval between stroke onset and assessment (<60 days). In previous studies, the frequency of cognitive impairment after unilateral PCA ischemic stroke ranged from 32% to 50%, similar to our findings.1,13,14 The association of cognitive impairment with left hemisphere stroke, advanced age, and low education level has been controversial.8,15,16 In a recent study, only stroke volume was related to post-stroke cognitive impairment, consistent with our findings.16 Although a longer follow-up investigation is required, the finding that cognitive decline within 2 months of acute PCA infarction is not associated with the time between stroke onset and assessment suggests that poor MMSE performance in the acute stage might predict long-term impairment. This study shows that parahippocampus or corpus callosum splenium involvement among the various combinations of occipital plus adjacent lesions contributes significantly to cognitive decline, whereas only 1 of 12 patients with isolated occipital lobe lesions had cognitive decline. Previous studies have shown that
parahippocampal or splenium damage causes multiple cognitive deficits. Parahippocampal cortex lesions have been implicated in memory and learning impairment,17,18 as well as visual neglect by disconnecting white matter between the parahippocampal gyrus and angular gyrus of the parietal lobe.19 Additionally, a few case studies have postulated that splenial lesions, such as a tumor or PCA stroke, are associated with neuropsychological abnormalities including amnesia, disorientation, topographical disturbance, and psychosis.20,21 The memory impairment observed in splenial damage is related to involvement of the retrosplenial cortex receiving input from the subiculum and projecting to the anterior thalamus.22 Furthermore, language disorder is associated with left occipital damage and interhemispheric associative fibers that traverse the splenium,23 and visual neglect occurs with a combined lesion of the right occipital lobe and splenium.24 In contrast, although thalamic lesions are frequently associated with cognitive impairment, the thalamus did not contribute to cognitive decline in our study.25 This discrepancy may be because only certain thalamic nuclei are associated with cognitive impairment when injured; furthermore, the thalamic lesions observed in our study were both small (mean ± SD; 1.23 ± 0.60 cm) and heterogeneous in location. This study had several limitations. First, detailed neuropsychological investigations were not undertaken in this study, and MMSE is insufficient to fully evaluate neuropsychological impairment after PCA infarction. Important neurological findings such as color anomia, agnosia, and prosopagnosia are not detected by MMSE. Also, for vascular cognitive impairment, other brief neuropsychological tests such as the 5 minute Montreal cognitive assessment may be preferable to MMSE because the former test is more sensitive to subtle memory impairment whereas MMSE assesses executive function only poorly.26 Second, CT scan results from 2 of 41 patients were grouped with MRI results even though small lesions are not well quantified from CT scans.26 However, we do not think this limitation affected our results because all patients in this study had large PCA territorial lesions. Third, we did not perform follow-up assessments of cognitive impairment. In this homogenous group with PCA infarction, periodic neuropsychological examinations are necessary to define the prognosis of cognitive impairment after vascular insults. Acknowledgement This study was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A050079). References 1. Brandt T, Steinke W, Andreas T, et al. Posterior cerebral artery territory infarcts: clinical features, infarct topography, causes and outcome. Cerebrovasc Dis 2000;10:170–82. 2. De Renzi E, Zambolin A, Crisi G. The pattern of neuropsychological impairment associated with left posterior cerebral artery infarcts. Brain 1987;110:1099–116. 3. Pillon B, Bakchine S, Lhermitte F. Alexia without agraphia in a left-handed patient with a right occipital lesion. Arch Neurol 1987;44:1257–62. 4. von Cramon DY, Hebel N, Schuri U. Verbal memory and learning in unilateral posterior cerebral infarction. A report on 30 cases. Brain 1988;111:1061–77. 5. Kumral E, Bayulkem G, Atac C, et al. Spectrum of superficial posterior cerebral artery territory infarcts. Eur J Neurol 2004;11:237–46. 6. Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993;43:250–60. 7. Auchus AP, Chen CP, Sodagar SN, et al. Single stroke dementia: insights from 12 cases in Singapore. J Neurol Sci 2002;203–4:85–9. 8. Szirmai I, Vastagh I, Szombathelyi E, et al. Strategic infarcts of the thalamus in vascular dementia. J Neurol Sci 2002;203–4:91–7. 9. Cals N, Devuyst G, Afsar N, et al. Pure superficial posterior cerebral artery territory infarction in The Lausanne Stroke Registry. J Neurol 2002;249: 855–61.
K.-C. Park et al. / Journal of Clinical Neuroscience 16 (2009) 914–917 10. Folstein MF, Folstein SE, McHugh PR. ‘Mini-Mental State’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98. 11. Mendez MF, Cummings JL. Mental status assessment. In: Dementia: A Clinical Approach, 3rd edn. Philadelphia: Butterworth Heinemann 2003: pp. 13–39. 12. Oldfield RC. The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia 1971;9:97–113. 13. Milandre L, Brosset C, Botti G, et al. A study of 82 cerebral infarctions in the area of posterior cerebral arteries. Rev Neurol (Paris) 1994;150:133–41. 14. Steinke W, Mangold J, Schwartz A, et al. Mechanisms of infarction in the superficial posterior artery territory. J Neurol 1997;244:571–8. 15. Pohjasvaara T, Erkinjuntti T, Ylikoski R, et al. Clinical determinants of poststroke dementia. Stroke 1998;29:75–81. 16. Sachdev PS, Brodaty H, Valenzuela MJ, et al. Clinical determinants of dementia and mild cognitive impairment following ischaemic stroke: the Sydney Stroke Study. Dement Geriatr Cogn Disord 2006;21:275–83. 17. Suzuki, Zola-Morgan S, Squire LR, et al. Lesions of the perirhinal and parahippocampal cortices in the monkey produce long-lasting memory impairment in the visual and tactual modalities. J Neurosci 1993;13:2430–51. 18. Zola-Morgan S, Squire LR, Amaral DG, et al. Lesions of perirhinal and parahippocampal cortex that spare the amygdala and hippocampal
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formation produce severe memory impairment. J Neurosci 1989;9: 4355–70. Bird CM, Malhotra P, Parton A, et al. Visual neglect after right posterior cerebral artery. J Neurol Neurosurg Psychiatry 2006;77:1008–12. Baumann CR, Regard M, Trier S, et al. Lipoma on the corpus callosum in a patient with schizophrenia-like episode: is there a causal relationship? Cogn Behav Neurol 2006;19:109–11. Osawa A, Maeshima S, Kubo K, et al. Neuropsychological deficits associated with a tumour in the posterior corpus callosum: a report of two cases. Brain Inj 2006;20:673–6. Valenstein E, Bowers D, Verfaellie M, et al. Retrosplenial amnesia. Brain 1987;110:1631–46. Damasio AR, Damasio H. The anatomic basis of pure alexia. Neurology 1983;33:1573–83. Park KC, Lee BH, Kim EJ, et al. Deafferentation–disconnection neglect induced by posterior cerebral artery infarction. Neurology 2006;66:55–61. Schmahmann JD. Vascular syndromes of the thalamus. Stroke 2003;34: 2264–78. Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 2006;37:2220–41.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Splenium or parahippocampus involvement and its relationship to cognitive decline in posterior cerebral artery infarction Key-Chung Park a,*, Sung-Sang Yoon a, Kyung-Hwa Seo b a b
Department of Neurology, Kyung Hee University, School of Medicine, 1 Hoegi-dong, Dongdaemoon-ku, Seoul, 130-702, Korea Department of Management, Kyung Hee University, Graduate College, Seoul, Korea
a r t i c l e
i n f o
Article history: Received 17 February 2008 Accepted 16 September 2008
Keywords: Cognitive decline MMSE Parahippocampus Posterior cerebral artery infarction Splenium
a b s t r a c t Although cognitive impairment after a posterior cerebral artery (PCA) infarct is frequently observed, the important functional areas associated with cognitive decline, other than the thalamus, have not been determined. We investigated the locus or loci that might induce cognitive decline after a PCA infarct. Forty-one patients with unilateral PCA infarctions involving only the occipital lobe or the occipital lobe plus other PCA areas were included. All subjects received a mini-mental status examination (MMSE) within 2 months of onset; 43.9% had cognitive impairment. The severity of cognitive impairment was not associated with left hemisphere lesion location, sex, age, education level, or the time between stroke and the MMSE assessment. Only the lesion volume was negatively correlated with MMSE score. Lesion location analysis revealed that an occipital plus splenial or parahippocampal lesion contributed to a decline in MMSE, which suggests that parahippocampal or splenial involvement with an occipital lesion is associated with the cognitive decline seen after PCA infarction. Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction Posterior cerebral artery (PCA) territory infarcts account for 5% to 10% of all strokes.1 Cognitive impairment after PCA infarcts is observed frequently and diverse neuropsychological deficits including dysphasia, amnesia, pure alexia, dyscalculia, visual neglect, and visual agnosia are described.1–5 A lesion localization study showed that vascular dementia was associated with PCA infarction of the paramedian thalamic or inferior medial temporal areas, and with lesions of the parieto-temporal or temporo-occipital territories.6 However, apart from the thalamus, other strategic areas within the PCA territory associated with cognitive decline have not been investigated.7,8 The development of MRI has allowed improved localization of lesion topography. The areas frequently involved in PCA infarcts are the occipital lobe, posterior ventral temporal lobe (fusiform and parahippocampal gyrus), thalamus, corpus callosum splenium, posterior cingulate gyrus, and retrosplenial cortex.1,9 We aimed to determine the locus or loci that might be involved in cognitive impairments after PCA infarction. We performed a lesion localization study in patients with PCA territory infarcts using
* Corresponding author. Tel.: +82 2 958 8447; fax: +82 2 958 8490. E-mail address: [email protected] (K.-C. Park). 0967-5868/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2008.09.010
mini-mental status examination (MMSE).10 The advantages of a MMSE are that it requires only 5 min to 10 min to evaluate the patient’s global cognitive state, and that the test is highly reliable between individual scorers and between tests.11
2. Methods 2.1. Patients The study included 41 patients (26 men and 15 women) with unilateral PCA infarctions involving the cerebral cortex. The mean age (±standard deviation [SD]) was 61.59 ± 14.15 years (range: 29– 87 years) with a mean (±SD) of 9.24 ± 4.32 years of education (range: 0–16 years). From April 2003 to September 2003, subjects were recruited consecutively from acute stroke units of four general hospitals in Seoul, Korea. Inclusion criteria were right-hand preference as assessed by Edinburgh Handedness Inventory,12 stroke onset less than 60 days prior, alertness, and cooperation. Exclusion criteria were prior stroke, aphasia severe enough to interfere with test taking, and a history of cognitive impairment. A complete neurological examination was performed and a neurologist, who was blinded to lesion location, assessed the MMSE. Cognitive impairment was defined as a score below 24 points on the MMSE. This study was performed in accordance with the ethical standards of the Declaration of Helsinki. All subjects provided informed consent.
915
K.-C. Park et al. / Journal of Clinical Neuroscience 16 (2009) 914–917
2.2. Lesion analysis In each scan section, the lesion boundary on CT scan (2/41) or T2-weighted MRI (39/41) was visually identified and outlined using a manual pixelwise method with the aid of a picture archiving and communication system (PACS) workstation (General Electric Medical Systems, Cincinatti, OH, USA). Lesion volume (in cm3) was calculated by multiplying the area of lesions in consecutive CT scan slices by the slice thickness, and in consecutive MRI slices by the slice thickness plus the interslice gap distance. A neurologist blinded to the patient’s clinical status measured the lesion volume.13 To define lesion location, two neurologists, unaware of clinical findings, coded the involved lesion as the occipital lobe, temporal fusiform gyrus, parahippocampal gyrus, corpus callosum splenium, thalamus, or posterior cingulate gyrus. 2.3. Statistical analysis We used an independent t-test and multiple linear regression models to investigate the relationship between sex, PCA lesion side and volume, age, years of education, time of stroke onset to MMSE test, severity of cognitive impairment (as indicated by continuous MMSE scores), and the presence of a lesion following infarction. To assess the relationship between lesion location and cognitive impairment (as categorized MMSE scores), we performed multiple
logistic regression. All statistical analyses were conducted using the Statistical Package for the Social Sciences version 13.0 (SPSS; Chicago, IL, USA). P < 0.05 was set as a two-tailed statistical significance level. 3. Results 3.1. Variables affecting MMSE score The mean time interval (±SD) between onset of infarction and brain imaging was 3.71 ± 3.23 days. Mean time (±SD) from onset of infarction to the MMSE test was 13.90 ± 14.84 days. The mean MMSE score was 22.98 ± 6.01. Twenty-four patients had right PCA infarction and 17 had left involvement. Motor power was normal in all patients, except for two patients with mild hemiparesis, which was above grade 4 on the Medical Research Council Scale for motor testing. Eighteen (43.9%) had cognitive impairment, defined as a MMSE score below 24 points. Cognitive decline after left and right PCA infarction occurred in 11 of 24 (45.8%) and 7 of 17 (41.2%) patients, respectively. Cognitive impairment severity (MMSE score) did not differ between right and left PCA infarctions (mean ± SD; right: 22.75 ± 6.22, left: 23.29 ± 5.87, t = 0.28, p = 0.779) or by sex (t = 1.46, p = 0.153). Impairment did not appear to be influenced by the interval between stroke onset and MMSE assessment (t = 1.85, p = 0.072), age (t = –0.93, p = 0.358), or level of education
Table 1 Demographics and clinical features of patients with PCA infarction (n = 41) Case Sex/age (years)
Onset (days)
Hemisphere
MMSE (total)
Stroke location
CT scan or MRI
Lesion volume (cm3)
1. M/58 2. M/73 3. F/35 4. M/70 5. M/36 6. M/30 7. F/29 8. M/67 9. M/54 10. M/70 11. M/71 12. M/64 13. F/38 14. M/57 15. F/61 16. F/56 17. M/53 18. M/44 19. M/49 20. M/87 21. M/45 22. F/69 23. M/63 24. M/69 25. M/59 26. M/70 27. M/73 28. F/57 29. F/80 30. F/68 31. M/73 32. F/70 33. F/69 34. M/54 35. F/68 36. M/65 37. F/71 38. M/83 39. M/77 40. F/66 41. F/75
4 7 4 59 49 19 17 29 9 16 12 3 1 8 8 1 5 1 20 6 3 6 59 33 20 21 16 26 4 7 34 5 1 11 4 8 3 1 6 8 16
Left Left Left Left Left Left Left Left Left Left Left Left Left Left Left Left Left Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right Right
25 17 29 27 29 25 30 25 27 28 24 29 15 9 18 19 19 27 27 25 29 27 30 27 25 24 26 27 15 24 13 17 27 24 24 30 14 25 7 17 15
O, O O O, O O, O, O, O, O, O, O O, O, O, O, O, O O, O, O O O, O O O, O, O O, O, O, O, O, O, O, O, O, O, O, O, O,
MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI CT MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI MRI CT
57.61 3.86 5.34 26.07 11.29 22.28 39.25 15.68 60.60 26.45 5.07 9.02 46.74 9.68 70.56 21.96 16.54 7.14 17.50 15.97 15.18 32.80 36.74 31.35 21.26 46.89 40.23 41.91 38.49 48.43 68.10 99.34 26.47 45.92 22.48 33.07 41.06 1.63 68.89 61.34 17.94
Fu, PH, Th
Spl Spl, Th CG Spl Fu, PH, Spl, Th Fu, PH Fu, PH, Spl Fu, PH, Spl, Th, CG Spl, Th, MB PH Fu, PH, Th, MB PH, Spl Spl CBLL
Fu, PH
PH, Spl Fu, PH PH, Th, CBLL Spl, CG, CBLL Fu, PH, Spl, Th Fu, PH, Spl, Th Fu Fu, PH, Spl, Th Fu, PH, Spl, Th Spl Fu, PH, Th CBLL Fu, PH, Spl, CG Fu, PH Fu, SplC)
CBLL = cerebellum, CG = cingulate gyrus, F = female, Fu = fusiform gyrus of temporal lobe, M = male, MB = midbrain, MMSE = Mini-mental status examination, O = occipital lobe, Onset = time from stroke onset to MMSE test, PH = parahippocampal gyrus, Spl = splenium, Th = thalamus.
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Table 2 The relationship between mini-mental status examination score and lesion locus Lesion locus Fusiform gyrus Parahippocampal gyrus Splenium Thalamus Cingulate gyrus
Crude odds ratio
p-value *
Adj. OR ,§
p-value
4.45 (1.18–16.81) 12.60 (2.84–55.84)
0.028 0.001**
4.40 (0.53–36.45) 99.92 (3.02–3303.68)
0.169 0.010*
5.67 (1.47–21.89) 6.67 (1.45–60.64) 4.40 (0.42–46.43)
0.012* 0.015* 0.218
133.84 (2.83–6320.86) 6.88 (0.77–61.22) 1.65 (0.06–49.31)
0.013* 0.084 0.774
*
p-value < 0.05. p-value < 0.01. Adjusted for sex, side of PCA lesion, age, duration of education, lesion volume, interval time from stroke onset to test assessment. PCA = posterior cerebral artery. 95% confidence intervals shown in brackets. ** §
(t = 1.67, p = 0.104). In contrast, only lesion volume showed a negative correlation with MMSE (t = –2.20, p = 0.035). 3.2. MMSE score and lesion loci relationship Lesion location analysis showed that the occipital lobe was affected in all patients. Of the 12 patients with lesions confined to the occipital lobe, only one had cognitive decline. The other lesion sites, in order of decreasing frequency, were the parahippocampal gyrus (19/41, 46.3%), corpus callosum splenium (18/41, 43.9%), temporal fusiform gyrus (17/41, 41.5%), thalamus (12/41, 29.3%), and posterior cingulate gyrus (4/41, 9.8%) (Table 1). Using multiple logistic regression analysis, we investigated the relationship between the loci of the injured area and cognitive impairment. No multi-colinearity existed between lesions and controlled variables. For regression analysis, sex, PCA lesion side, age, lesion volume, education duration, and period from stroke onset to assessment were adjusted. All candidate lesions (fusiform gyrus, parahippocampal gyrus, splenium, thalamus, and posterior cingulate gyrus) were used in a multiple logistic regression model with MMSE scores. Analysis revealed that the splenium and parahippocampal gyrus were associated with cognitive impairment when other factors affecting MMSE scores were adjusted (splenium: adjusted odds ratio = 133.84, CI 2.83–6320.86, p = 0.013; parahippocampal gyrus: adjusted odds ratio = 99.92, CI 3.02–3303.68, p = 0.010) (Table 2). 4. Discussion In our study, the frequency of cognitive decline after a first episode of acute occipital or occipital plus other region infarctions in the PCA territory was 43.9%. Cognitive impairment was influenced by larger lesion volume and was not influenced by age, sex, lesion location (left versus right), level of education, or interval between stroke onset and assessment (<60 days). In previous studies, the frequency of cognitive impairment after unilateral PCA ischemic stroke ranged from 32% to 50%, similar to our findings.1,13,14 The association of cognitive impairment with left hemisphere stroke, advanced age, and low education level has been controversial.8,15,16 In a recent study, only stroke volume was related to post-stroke cognitive impairment, consistent with our findings.16 Although a longer follow-up investigation is required, the finding that cognitive decline within 2 months of acute PCA infarction is not associated with the time between stroke onset and assessment suggests that poor MMSE performance in the acute stage might predict long-term impairment. This study shows that parahippocampus or corpus callosum splenium involvement among the various combinations of occipital plus adjacent lesions contributes significantly to cognitive decline, whereas only 1 of 12 patients with isolated occipital lobe lesions had cognitive decline. Previous studies have shown that
parahippocampal or splenium damage causes multiple cognitive deficits. Parahippocampal cortex lesions have been implicated in memory and learning impairment,17,18 as well as visual neglect by disconnecting white matter between the parahippocampal gyrus and angular gyrus of the parietal lobe.19 Additionally, a few case studies have postulated that splenial lesions, such as a tumor or PCA stroke, are associated with neuropsychological abnormalities including amnesia, disorientation, topographical disturbance, and psychosis.20,21 The memory impairment observed in splenial damage is related to involvement of the retrosplenial cortex receiving input from the subiculum and projecting to the anterior thalamus.22 Furthermore, language disorder is associated with left occipital damage and interhemispheric associative fibers that traverse the splenium,23 and visual neglect occurs with a combined lesion of the right occipital lobe and splenium.24 In contrast, although thalamic lesions are frequently associated with cognitive impairment, the thalamus did not contribute to cognitive decline in our study.25 This discrepancy may be because only certain thalamic nuclei are associated with cognitive impairment when injured; furthermore, the thalamic lesions observed in our study were both small (mean ± SD; 1.23 ± 0.60 cm) and heterogeneous in location. This study had several limitations. First, detailed neuropsychological investigations were not undertaken in this study, and MMSE is insufficient to fully evaluate neuropsychological impairment after PCA infarction. Important neurological findings such as color anomia, agnosia, and prosopagnosia are not detected by MMSE. Also, for vascular cognitive impairment, other brief neuropsychological tests such as the 5 minute Montreal cognitive assessment may be preferable to MMSE because the former test is more sensitive to subtle memory impairment whereas MMSE assesses executive function only poorly.26 Second, CT scan results from 2 of 41 patients were grouped with MRI results even though small lesions are not well quantified from CT scans.26 However, we do not think this limitation affected our results because all patients in this study had large PCA territorial lesions. Third, we did not perform follow-up assessments of cognitive impairment. In this homogenous group with PCA infarction, periodic neuropsychological examinations are necessary to define the prognosis of cognitive impairment after vascular insults. Acknowledgement This study was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A050079). References 1. Brandt T, Steinke W, Andreas T, et al. Posterior cerebral artery territory infarcts: clinical features, infarct topography, causes and outcome. Cerebrovasc Dis 2000;10:170–82. 2. De Renzi E, Zambolin A, Crisi G. The pattern of neuropsychological impairment associated with left posterior cerebral artery infarcts. Brain 1987;110:1099–116. 3. Pillon B, Bakchine S, Lhermitte F. Alexia without agraphia in a left-handed patient with a right occipital lesion. Arch Neurol 1987;44:1257–62. 4. von Cramon DY, Hebel N, Schuri U. Verbal memory and learning in unilateral posterior cerebral infarction. A report on 30 cases. Brain 1988;111:1061–77. 5. Kumral E, Bayulkem G, Atac C, et al. Spectrum of superficial posterior cerebral artery territory infarcts. Eur J Neurol 2004;11:237–46. 6. Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993;43:250–60. 7. Auchus AP, Chen CP, Sodagar SN, et al. Single stroke dementia: insights from 12 cases in Singapore. J Neurol Sci 2002;203–4:85–9. 8. Szirmai I, Vastagh I, Szombathelyi E, et al. Strategic infarcts of the thalamus in vascular dementia. J Neurol Sci 2002;203–4:91–7. 9. Cals N, Devuyst G, Afsar N, et al. Pure superficial posterior cerebral artery territory infarction in The Lausanne Stroke Registry. J Neurol 2002;249: 855–61.
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