- Email: [email protected]
Proton magnetic resonance spectroscopy in children with spastic diplegia
Neuroscience Letters 363 (2004) 62–64 www.elsevier.com/locate/neulet
Proton magnetic resonance spectroscopy in children with spastic diplegia Wojciech Kulaka,*, Wojciech Sobanieca, Bozena Kubasb, Jerzy Waleckib a
Department of Pediatric Neurology, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland Department of Radiology, Medical University of Bialystok, M. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland
b
Received 20 October 2003; received in revised form 31 January 2004; accepted 19 March 2004
Abstract The objective of this prospective study was the application of proton magnetic resonance spectroscopy in children with spastic diplegia (SD) to determine the metabolite profile of SD children in the left basal ganglia, and to assess the relationship of this profile with motor and mental development. Patients with SD showed reduced ratios of N-acetylaspartate (NAA)/creatine (Cr), NAA/choline (Cho), NAA/myoinositol (mI), Cho/NAA, Cho/Cr and Cho/mI in the basal ganglia compared to a well-matched control group. On the other hand, we noted increased Cr/NAA, Cr/Cho and mI/NAA ratios in the SD patients as compared with controls. NAA/mI ratios were positively correlated with the severity scale of cerebral palsy in SD children. There was also a significant correlation between Cr/NAA and mental retardation. Increased Cr/NAA, Cr/Cho and mI/NAA ratios in SD children may suggest the existence of the compensatory mechanisms in these patients. The NAA/mI ratio could be used as an additional marker of SD severity and Cr/NAA as a marker of the mental retardation. q 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Proton magnetic resonance spectroscopy; Basal ganglia; Cerebral palsy; Spastic diplegia
Cerebral palsy (CP) is a chronic disorder of movement and posture caused by non-progressive damage to the developing brain, which occurs prenatally, perinatally or postnatally. Patients with CP may have some problems other than this motor impairment, such as mental retardation, epilepsy and sensory disturbance [8,11]. Spastic diplegia (SD) is the most common form of CP. The basal ganglia, and more specifically the corpus striatum, play a central role in the feedback loop that modulates cerebral cortical function [15]. Disruption of cortico-striatal pathways seems to be of particular importance with regard to neurobehavioral abnormalities [3]. This is highly relevant in CP children because for several reasons the basal ganglia are vulnerable to injury during a restricted period in brain development [7,14]. Proton magnetic resonance spectroscopy (1H-MRS) is widely applied in the determination and differentiation of brain tumors, hypoxia, post-radiotherapy changes and other lesions mimicking neoplasm-like abscesses [2,4,13,16,17]. 1H-MRS has proven to be a useful tool for the early evaluation of brain injury in asphyxiated neonates [8,9]. High lactate (Lac) levels and low Nacetylaspartate (NAA) levels are the most common findings. A fall in the NAA/choline (Cho) ratio also indicates an adverse prognosis. NAA is a neuronal marker and the other metabolites can be viewed as cerebral indicators of energy metabolism creatine (Cr) and of cytoplasmic Lac and * Corresponding author. Tel.: þ 48-85-7450812; fax: þ 48-85-7450812. E-mail address: [email protected] (W. Kulak).
mitochondrial (Glx) redox state. Myo-inositol (mI) is a precursor for the phosphatidylinositol second messenger system, and it regulates osmotic processes within the brain and takes part in mood states. Pronounced elevation of mI may reflect demyelination and glial proliferation. The decrease in the NAA/Cr ratio may indicate neuroaxonal damage or deficient neuronal formation [12,13]. The increased Cho/Cr and mI/Cr levels, which could indicate increased membrane turnover and myelin breakdown and astrocytosis, respectively, might correspond to glial cell proliferation [10,16]. The NAA/Cho and NAA/Cr ratios are lower in patients with mental retardation than in controls [6]. Only in one study, that of Kra¨geloh-Mann et al. [7], was 1 H-MRS performed on two children with dyskinetic CP. They found a decrease in NAA/Cr and Cho/Cr ratios in the basal ganglia. To our knowledge, no MRS study has been conducted in children with SD. The objective of this prospective study was the application of 1H-MRS to children with SD: (a) to determine the metabolite profile of SD children in the basal ganglia; and (b) to assess the relationship of this profile with motor and mental development. The study was approved by the local Ethical Committee. The present study included 19 children with SD and 19 healthy matched control subjects (details are summarized in Table 1). The children with SD are under the care of the Department of Pediatric Neurology in Bialystok. A group of
0304-3940/03/$ - see front matter q 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.03.043
W. Kulak et al. / Neuroscience Letters 363 (2004) 62–64 Table 1 Clinical data of children with SD and controls
Table 2 Metabolite ratios in the left basal ganglia in children with SD and the control group (mean ^ standard deviation)
Data
SD (n ¼ 19)
Controls (n ¼ 19)
Age (years) (range 4– 15) Gender Boys Girls Gestation (weeks) (25–41) Delivery Term , 37 tyg. Apgar scores (1–10) 5–10 0–4 (asphyxia) Birth weight (g)
9.44 ^ 4.85
9.89 ^ 4.40
10 9 25– 41 35.40 ^ 5.43
9 10 35–42 38.2 ^ 1.69
12 7 6.04 ^ 3.95
17 2 8.90 ^ 1.80
Low birth weight (,2500 g) Normal birth weight (.2500 g)
1400–4500 2736 ^ 1045 7 12
63
2800–4480 3400 ^ 450 0 19
19 healthy children matched for age, sex, and social background were recruited as a comparison group. SD was defined as motor disabilities caused by non-progressive damage to the developing brain [11]. The degree of CP severity was assessed in our patients according to Arguelles et al. [1]: 3, very severe, when patients do not have any postural control; 2, severe, can walk with maximum support; 1, moderate, can walk with some support; 0, mild, can walk unaided. All the children in this group had one or more formal psychological assessments (the typical Wechsler Intelligence Scale for Children, Polish version). Mentally handicapped – formal psychological testing results indicated function in the mentally deficient range. Mental retardation was divided into mild (IQ 70–84), moderate (IQ 50–69) and severe (IQ ,50). Normal children had an IQ of .90. All MR scans were obtained using a 1.5 T MR scanner (Picker Edge Eclipse) with use of a standard circular polarized head coil. Imaging sequences with T1-weighted FAST scan (TR 300 ms, TE 4.5, 5 mm thick sections) pre-
Metabolites
SD group (n ¼ 19)
Control group (n ¼ 19)
t value
P value
NAA/Cr NAA/Cho NAA/mI
1.63 ^ 0.18 1.98 ^ 0.26 3.08 ^ 0.68
1.99 ^ 0.16 2.17 ^ 0.17 3.84 ^ 0.70
5.95 2.58 3.33
,0.001 ,0.05 ,0.01
Cr/NAA Cr/Cho Cr/mI
0.59 ^ 0.06 1.15 ^ 0.13 1.87 ^ 0.38
0.49 ^ 0.02 1.06 ^ 0.10 1.92 ^ 0.37
5.43 2.11 0.45
,0.001 ,0.05 NS
Cho/NAA Cho/Cr Cho/mI
0.51 ^ 0.06 0.87 ^ 0.09 1.59 ^ 0.33
0.47 ^ 0.04 0.95 ^ 0.10 1.81 ^ 0.27
2.28 2.31 2.17
,0.05 ,0.05 ,0.05
mI/NAA mI/Cr mI/Cho
0.33 ^ 0.07 0.58 ^ 0.13 0.66 ^ 0.66
0.26 ^ 0.04 0.53 ^ 0.07 0.57 ^ 0.11
3.55 1.43 1.62
,0.01 NS NS
Two tailed t-test; NS, not significant.
and post i.v. contrast media administration (0.1 mmol/kg, Megnevist, Schering) were performed. FSE T2-weighted and FLAIR series (TR 5000 ms, TE 127.6, 5 mm thick sections) were used. For 1H-MRS single voxel PRESS sequence, with TR 1500 ms, TE 35 ms, NEX 192, 2 kHz bandwidth, and a single-voxel (2 £ 2 £ 2 cm3) located in the left basal ganglia (thalamus, capsula interna) from an axial section, the MOIST method for suppressing the water signal was applied. Spectroscopic data were analyzed using the Via 2.0 C (Picker) software package. In the spectrum estimation, signals of NAA were obtained at 2.01 parts per million (ppm), with Cr at 3.0 ppm, Cho at 3.22 ppm, and mI at 3.55 ppm (Fig. 1). Peak area metabolite ratios (NAA/Cr, NAA/Cho, NAA/mI, Cr/NAA, Cr/Cho, Cr/mI, Cho/NAA, Cho/Cr, Cho/mI, mI/NAA, mI/Cr, mI/Cho) were calculated. This is the first study of 1H-MRS in SD patients, so we used all the possible ratios. The total study time averaged 30– 40 min. Barbiturate anesthesia does not interfere with the main visible brain metabolites measured during 1H-MRS [9].
Fig. 1. 1H-MRS of the left basal ganglia in controls and patients. Metabolite resonances refer to NAA, Cr, Cho and mI.
64
W. Kulak et al. / Neuroscience Letters 363 (2004) 62–64
Four children needed sedation. We used thiopental (3 mg/kg body weight i.v.) in anesthesia. We used Student’s t-test for independent samples to compare the means from the groups in the 1H-MRS variables. Spearman’s rank test was used to measure the strength of association between metabolite ratios and the severity scale of CP and mental development. For all the analyses, we used the two-tailed significance (P , 0:05). Seventeen SD children had hypoxic-ischemic lesions with patterns of periventricular leucomalacia, subcortical lesions or cortical infarction in MR. Two patients had normal MR scans. The reduced ratios of NAA/Cr, NAA/Cho, NAA/mI, Cho/NAA, Cho/Cr and Cho/mI of SD children and controls in the basal ganglia differed significantly (Table 2). On the other hand, we noted increased ratios of Cr/NAA, Cr/Cho and mI/NAA in the SD patients as compared with the controls. NAA/mI ratios (r ¼ 0:584, P , 0:01) were positively correlated with the severity scale of CP in SD children. Cr/NAA ratios (r ¼ 0:516, P , 0:05) were significantly correlated with mental retardation in SD patients. Current research suggests that clearly a relationship exists between normal brain function and NAA, and that monitoring the level of NAA may provide important information about brain function [6]. It has been suggested that NAA may also be lost from neurons still functioning as a result of alterations in the brain [6]. Previous studies of perinatal asphyxia (PA) using 1H-MRS have shown that NAA/Cho ratios are significantly lower in patients with an adverse outcome than in survivors without handicaps [5] and that this ratio relates to neuromotor and cognitive performances at 12 months of age. Our results also support those of Maneru et al. [10] and Barkovich et al. [2]. In this study, we also found a decrease of NAA/Cho ratios as compared with the control group. Maneru et al. [10] performed a 1H-MRS study in patients aged from 13 to 21 years with antecedents of PA. Patients with PA showed reduced values of NAA in both the basal ganglia, which is consistent with our findings. Neuropsychological testing showed group differences in tasks related to attention and memory. We found that the Cr/NAA ratios were correlated with mental development. Some limitations of this study should be mentioned. The study was performed on 19 children with SD. It would, however, be desirable to obtain new data from a larger group. A multivoxel 1H-MRS approach would be of great interest to assess other cerebral regions involved in CP. In conclusion, the present findings showed reduced values of NAA and Cho in the basal ganglia in SD children. This may be indicative of neuronal loss subsequent to an anoxic episode during the prenatal or perinatal periods. On the other hand, elevated Cr values in SD children may reflect an increase in the metabolism in the basal ganglia. The increased mI/NAA ratios suggest the existence of gliosis in the patients examined. The NAA/mI ratios were
positively correlated with the severity scale of CP in SD children. The Cr/NAA ratios were significantly correlated with mental retardation in SD patients.
References [1] P.P. Arguelles, J.M. Lima, F.S. Vilaplana, Epilepsia en nin˜os com para´lisis cerebral, Acta Pediatr. Esp. 53 (1995) 304– 308. [2] A.J. Barkovich, K. Baranski, D. Vigneron, J.C. Partridge, D.K. Hallam, B.L. Hajnal, D.M. Ferriero, Proton MR spectroscopy for the evaluation of brain injury in asphyxiated, term neonates, AJNR Am. J. Neuroradiol. 20 (1999) 1399– 1405. [3] B. Brouwer, P. Ashby, Do injuries to the developing human brain alter corticospinal projections?, Neurosci. Lett. 189 (1990) 225–230. [4] P. Gideon, B. Sperling, P. Arlien-Soborg, T.S. Olsen, O. Henriksen, Long-term follow-up of cerebral infarction patients with proton magnetic resonance spectroscopy, Stroke 25 (1994) 967–973. [5] D.F. Groenendaal, R. Veenhoven, J. Van der Grond, G.H. Jansen, T. Witkamp, L.S. De Vries, Cerebral lactate and N-acetyl-aspartate/ choline ratios in asphyxiated full-term neonates demonstrated in vivo using proton magnetic resonance spectroscopy, Pediatr. Res. 35 (1994) 148 –151. [6] T. Hashimoto, M. Tayama, M. Miyazaki, Y. Yoneda, T. Yoshimoto, M. Harada, H. Miyoshi, M. Tanouchi, Y. Kuroda, Reduced Nacetylaspartate in the brain observed on in vivo proton magnetic resonance spectroscopy in patients with mental retardation, Pediatr. Neurol. 13 (1995) 205–208. [7] I. Kra¨geloh-Mann, A. Helber, I. Mader, M. Staudt, M. Wolff, F. Groenendaal, L.S. De Vries, Bilateral lesions of thalamus and basal ganglia: origin and outcome, Dev. Med. Child Neurol. 44 (2002) 477 –484. [8] W. Kulak, W. Sobaniec, Risk factors and prognosis of epilepsy in children with cerebral palsy in north-eastern Poland, Brain Dev. 45 (2003) 499 –506. [9] N.M. Lundbom, T. Manner, M. Komu, O. Peltola, K.A. Leino, O.A. Kirvela, Barbiturate anesthesia and brain proton spectroscopy, AJNR Am. J. Neuroradiol. 20 (1999) 1543–1546. [10] C. Maneru, C. Junque, N. Bargallo, M. Olondo, F. Botet, M. Tallada, J. Guardia, J.M. Mercader, (1)H-MR spectroscopy is sensitive to subtle effects of perinatal asphyxia, Neurology 25 (2001) 1115– 1118. [11] L. Mutch, E. Alberman, B. Hagberg, K. Kodama, M.V. Perat, Cerebral palsy epidemiology: where are we now and where are we going?, Dev. Med. Child Neurol. 34 (1992) 547– 555. [12] E. Novotny, S. Ashwal, M. Shevell, Proton magnetic resonance spectroscopy: an emerging technology in pediatric neurology research, Pediatr. Res. 44 (1998) 1–10. [13] S.G. Pavlakis, P.B. Kingsley, R. Harper, S. Buckwald, R. Spinazzola, Y. Frank, I. Prohovnik, Correlation of basal ganglia magnetic resonance spectroscopy with Apgar score in perinatal asphyxia, Arch. Neurol. 56 (1999) 1476–1481. [14] Z. Seidl, J. Sussova, J. Obenberger, M. Vaneckova, T. Vitak, J. Rydland, Magnetic resonance imaging in diplegic form of cerebral palsy, Brain Dev. 34 (2001) 46–49. [15] S.M. Sherman, R.W. Guillery, The role of the thalamus in the flow of information to the cortex, Phil. Trans. R. Soc. London B Biol. Sci. 357 (2002) 1695–1708. [16] S.K. Shu, S. Ashwal, B.A. Holshouser, G. Nystrom, D.B. Hinshaw Jr., Prognostic value of 1H-MRS in perinatal CNS insults, Pediatr. Neurol. 17 (1997) 309–318. [17] E. Tarasow, A. Wiercinska-Drapalo, B. Kubas, W. Dzienis, A. Orzechowska-Bobkiewicz, D. Prokopowicz, J. Walecki, Cerebral MR spectroscopy in neurologically asymptomatic HIV-infected patients, Acta Radiol. 44 (2003) 206–212.
Proton magnetic resonance spectroscopy in children with spastic diplegia Wojciech Kulaka,*, Wojciech Sobanieca, Bozena Kubasb, Jerzy Waleckib a
Department of Pediatric Neurology, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland Department of Radiology, Medical University of Bialystok, M. Sklodowskiej-Curie 24a, 15-276 Bialystok, Poland
b
Received 20 October 2003; received in revised form 31 January 2004; accepted 19 March 2004
Abstract The objective of this prospective study was the application of proton magnetic resonance spectroscopy in children with spastic diplegia (SD) to determine the metabolite profile of SD children in the left basal ganglia, and to assess the relationship of this profile with motor and mental development. Patients with SD showed reduced ratios of N-acetylaspartate (NAA)/creatine (Cr), NAA/choline (Cho), NAA/myoinositol (mI), Cho/NAA, Cho/Cr and Cho/mI in the basal ganglia compared to a well-matched control group. On the other hand, we noted increased Cr/NAA, Cr/Cho and mI/NAA ratios in the SD patients as compared with controls. NAA/mI ratios were positively correlated with the severity scale of cerebral palsy in SD children. There was also a significant correlation between Cr/NAA and mental retardation. Increased Cr/NAA, Cr/Cho and mI/NAA ratios in SD children may suggest the existence of the compensatory mechanisms in these patients. The NAA/mI ratio could be used as an additional marker of SD severity and Cr/NAA as a marker of the mental retardation. q 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Proton magnetic resonance spectroscopy; Basal ganglia; Cerebral palsy; Spastic diplegia
Cerebral palsy (CP) is a chronic disorder of movement and posture caused by non-progressive damage to the developing brain, which occurs prenatally, perinatally or postnatally. Patients with CP may have some problems other than this motor impairment, such as mental retardation, epilepsy and sensory disturbance [8,11]. Spastic diplegia (SD) is the most common form of CP. The basal ganglia, and more specifically the corpus striatum, play a central role in the feedback loop that modulates cerebral cortical function [15]. Disruption of cortico-striatal pathways seems to be of particular importance with regard to neurobehavioral abnormalities [3]. This is highly relevant in CP children because for several reasons the basal ganglia are vulnerable to injury during a restricted period in brain development [7,14]. Proton magnetic resonance spectroscopy (1H-MRS) is widely applied in the determination and differentiation of brain tumors, hypoxia, post-radiotherapy changes and other lesions mimicking neoplasm-like abscesses [2,4,13,16,17]. 1H-MRS has proven to be a useful tool for the early evaluation of brain injury in asphyxiated neonates [8,9]. High lactate (Lac) levels and low Nacetylaspartate (NAA) levels are the most common findings. A fall in the NAA/choline (Cho) ratio also indicates an adverse prognosis. NAA is a neuronal marker and the other metabolites can be viewed as cerebral indicators of energy metabolism creatine (Cr) and of cytoplasmic Lac and * Corresponding author. Tel.: þ 48-85-7450812; fax: þ 48-85-7450812. E-mail address: [email protected] (W. Kulak).
mitochondrial (Glx) redox state. Myo-inositol (mI) is a precursor for the phosphatidylinositol second messenger system, and it regulates osmotic processes within the brain and takes part in mood states. Pronounced elevation of mI may reflect demyelination and glial proliferation. The decrease in the NAA/Cr ratio may indicate neuroaxonal damage or deficient neuronal formation [12,13]. The increased Cho/Cr and mI/Cr levels, which could indicate increased membrane turnover and myelin breakdown and astrocytosis, respectively, might correspond to glial cell proliferation [10,16]. The NAA/Cho and NAA/Cr ratios are lower in patients with mental retardation than in controls [6]. Only in one study, that of Kra¨geloh-Mann et al. [7], was 1 H-MRS performed on two children with dyskinetic CP. They found a decrease in NAA/Cr and Cho/Cr ratios in the basal ganglia. To our knowledge, no MRS study has been conducted in children with SD. The objective of this prospective study was the application of 1H-MRS to children with SD: (a) to determine the metabolite profile of SD children in the basal ganglia; and (b) to assess the relationship of this profile with motor and mental development. The study was approved by the local Ethical Committee. The present study included 19 children with SD and 19 healthy matched control subjects (details are summarized in Table 1). The children with SD are under the care of the Department of Pediatric Neurology in Bialystok. A group of
0304-3940/03/$ - see front matter q 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.03.043
W. Kulak et al. / Neuroscience Letters 363 (2004) 62–64 Table 1 Clinical data of children with SD and controls
Table 2 Metabolite ratios in the left basal ganglia in children with SD and the control group (mean ^ standard deviation)
Data
SD (n ¼ 19)
Controls (n ¼ 19)
Age (years) (range 4– 15) Gender Boys Girls Gestation (weeks) (25–41) Delivery Term , 37 tyg. Apgar scores (1–10) 5–10 0–4 (asphyxia) Birth weight (g)
9.44 ^ 4.85
9.89 ^ 4.40
10 9 25– 41 35.40 ^ 5.43
9 10 35–42 38.2 ^ 1.69
12 7 6.04 ^ 3.95
17 2 8.90 ^ 1.80
Low birth weight (,2500 g) Normal birth weight (.2500 g)
1400–4500 2736 ^ 1045 7 12
63
2800–4480 3400 ^ 450 0 19
19 healthy children matched for age, sex, and social background were recruited as a comparison group. SD was defined as motor disabilities caused by non-progressive damage to the developing brain [11]. The degree of CP severity was assessed in our patients according to Arguelles et al. [1]: 3, very severe, when patients do not have any postural control; 2, severe, can walk with maximum support; 1, moderate, can walk with some support; 0, mild, can walk unaided. All the children in this group had one or more formal psychological assessments (the typical Wechsler Intelligence Scale for Children, Polish version). Mentally handicapped – formal psychological testing results indicated function in the mentally deficient range. Mental retardation was divided into mild (IQ 70–84), moderate (IQ 50–69) and severe (IQ ,50). Normal children had an IQ of .90. All MR scans were obtained using a 1.5 T MR scanner (Picker Edge Eclipse) with use of a standard circular polarized head coil. Imaging sequences with T1-weighted FAST scan (TR 300 ms, TE 4.5, 5 mm thick sections) pre-
Metabolites
SD group (n ¼ 19)
Control group (n ¼ 19)
t value
P value
NAA/Cr NAA/Cho NAA/mI
1.63 ^ 0.18 1.98 ^ 0.26 3.08 ^ 0.68
1.99 ^ 0.16 2.17 ^ 0.17 3.84 ^ 0.70
5.95 2.58 3.33
,0.001 ,0.05 ,0.01
Cr/NAA Cr/Cho Cr/mI
0.59 ^ 0.06 1.15 ^ 0.13 1.87 ^ 0.38
0.49 ^ 0.02 1.06 ^ 0.10 1.92 ^ 0.37
5.43 2.11 0.45
,0.001 ,0.05 NS
Cho/NAA Cho/Cr Cho/mI
0.51 ^ 0.06 0.87 ^ 0.09 1.59 ^ 0.33
0.47 ^ 0.04 0.95 ^ 0.10 1.81 ^ 0.27
2.28 2.31 2.17
,0.05 ,0.05 ,0.05
mI/NAA mI/Cr mI/Cho
0.33 ^ 0.07 0.58 ^ 0.13 0.66 ^ 0.66
0.26 ^ 0.04 0.53 ^ 0.07 0.57 ^ 0.11
3.55 1.43 1.62
,0.01 NS NS
Two tailed t-test; NS, not significant.
and post i.v. contrast media administration (0.1 mmol/kg, Megnevist, Schering) were performed. FSE T2-weighted and FLAIR series (TR 5000 ms, TE 127.6, 5 mm thick sections) were used. For 1H-MRS single voxel PRESS sequence, with TR 1500 ms, TE 35 ms, NEX 192, 2 kHz bandwidth, and a single-voxel (2 £ 2 £ 2 cm3) located in the left basal ganglia (thalamus, capsula interna) from an axial section, the MOIST method for suppressing the water signal was applied. Spectroscopic data were analyzed using the Via 2.0 C (Picker) software package. In the spectrum estimation, signals of NAA were obtained at 2.01 parts per million (ppm), with Cr at 3.0 ppm, Cho at 3.22 ppm, and mI at 3.55 ppm (Fig. 1). Peak area metabolite ratios (NAA/Cr, NAA/Cho, NAA/mI, Cr/NAA, Cr/Cho, Cr/mI, Cho/NAA, Cho/Cr, Cho/mI, mI/NAA, mI/Cr, mI/Cho) were calculated. This is the first study of 1H-MRS in SD patients, so we used all the possible ratios. The total study time averaged 30– 40 min. Barbiturate anesthesia does not interfere with the main visible brain metabolites measured during 1H-MRS [9].
Fig. 1. 1H-MRS of the left basal ganglia in controls and patients. Metabolite resonances refer to NAA, Cr, Cho and mI.
64
W. Kulak et al. / Neuroscience Letters 363 (2004) 62–64
Four children needed sedation. We used thiopental (3 mg/kg body weight i.v.) in anesthesia. We used Student’s t-test for independent samples to compare the means from the groups in the 1H-MRS variables. Spearman’s rank test was used to measure the strength of association between metabolite ratios and the severity scale of CP and mental development. For all the analyses, we used the two-tailed significance (P , 0:05). Seventeen SD children had hypoxic-ischemic lesions with patterns of periventricular leucomalacia, subcortical lesions or cortical infarction in MR. Two patients had normal MR scans. The reduced ratios of NAA/Cr, NAA/Cho, NAA/mI, Cho/NAA, Cho/Cr and Cho/mI of SD children and controls in the basal ganglia differed significantly (Table 2). On the other hand, we noted increased ratios of Cr/NAA, Cr/Cho and mI/NAA in the SD patients as compared with the controls. NAA/mI ratios (r ¼ 0:584, P , 0:01) were positively correlated with the severity scale of CP in SD children. Cr/NAA ratios (r ¼ 0:516, P , 0:05) were significantly correlated with mental retardation in SD patients. Current research suggests that clearly a relationship exists between normal brain function and NAA, and that monitoring the level of NAA may provide important information about brain function [6]. It has been suggested that NAA may also be lost from neurons still functioning as a result of alterations in the brain [6]. Previous studies of perinatal asphyxia (PA) using 1H-MRS have shown that NAA/Cho ratios are significantly lower in patients with an adverse outcome than in survivors without handicaps [5] and that this ratio relates to neuromotor and cognitive performances at 12 months of age. Our results also support those of Maneru et al. [10] and Barkovich et al. [2]. In this study, we also found a decrease of NAA/Cho ratios as compared with the control group. Maneru et al. [10] performed a 1H-MRS study in patients aged from 13 to 21 years with antecedents of PA. Patients with PA showed reduced values of NAA in both the basal ganglia, which is consistent with our findings. Neuropsychological testing showed group differences in tasks related to attention and memory. We found that the Cr/NAA ratios were correlated with mental development. Some limitations of this study should be mentioned. The study was performed on 19 children with SD. It would, however, be desirable to obtain new data from a larger group. A multivoxel 1H-MRS approach would be of great interest to assess other cerebral regions involved in CP. In conclusion, the present findings showed reduced values of NAA and Cho in the basal ganglia in SD children. This may be indicative of neuronal loss subsequent to an anoxic episode during the prenatal or perinatal periods. On the other hand, elevated Cr values in SD children may reflect an increase in the metabolism in the basal ganglia. The increased mI/NAA ratios suggest the existence of gliosis in the patients examined. The NAA/mI ratios were
positively correlated with the severity scale of CP in SD children. The Cr/NAA ratios were significantly correlated with mental retardation in SD patients.
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