- Email: [email protected]
Delayed Myelination at the Onset of Cryptogenic West Syndrome
Delayed Myelination at the Onset of Cryptogenic West Syndrome Tomoyuki Takano, MD, Anri Hayashi, MD, Tatsuyuki Sokoda, MD, Chihiro Sawai, MD, Yuko Sakaue, MD, and Yoshihiro Takeuchi, MD To evaluate the prognostic value of delayed myelination at the onset of cryptogenic West syndrome, the relationship between the seizure or developmental outcome and myelination was examined. Cranial magnetic resonance imaging studies were performed in nine cryptogenic cases. Infantile spasms were controlled in all patients, but three cases showed a mild developmental delay at 2 years after onset. Delayed myelination was observed in three cases (33.3%) on T1-weighted images and in two cases (22.2%) on T2-weighted images. In the present study, neither the seizure outcome nor developmental status was positively correlated with the existence of delayed myelination at the onset of cryptogenic West syndrome. © 2007 by Elsevier Inc. All rights reserved. Takano T, Hayashi A, Sokoda T, Sawai C, Sakaue Y, Takeuchi Y. Delayed myelination at the onset of cryptogenic West syndrome. Pediatr Neurol 2007;37:417-420.
Introduction West syndrome is characterized by infantile spasms, hypsarrhythmia, and intellectual disability. This syndrome is classified within two etiologic groups, as symptomatic and cryptogenic, in the International Classification of Epilepsies and Epileptic Syndromes [1]. The cryptogenic group does not present any observable underlying cerebral lesion, whereas the symptomatic group has pre-existing brain damage. The most common pre-existing brain abnormalities that are visualized by magnetic resonance imaging are a thinning of the corpus callosum, dilatation of the cerebral ventricles, delayed myelination, lesions of diencephalic deep gray matter, and an enlargement of the subarachnoid space [2]. However, delayed myelination appears to be independent of any specific etiology, and it
From Department of Pediatrics, Shiga University of Medical Science, Seta-Tsukinowa, Otsu 520-2192, Japan.
© 2007 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2007.06.021 ● 0887-8994/07/$—see front matter
is sometimes difficult to assess in the absence of neuropathological investigations [3]. Idiopathic West syndrome has been previously reported to occur in a normal child; the hypsarrhythmic pattern is typical and symmetric, and it reappears between individual spasms during clusters [4]. Even in idiopathic West syndrome, which is expected to be a more benign outcome, delayed myelination has been observed in about half of all patients [5]. In children with cryptogenic West syndrome and with tuberous sclerosis, myelination has been reported to be either normal or only mildly delayed in the first month after the onset of the spasms, but delayed myelination seems to increase in the course of the West syndrome [6]. To evaluate the prognostic value of delayed myelination at onset, the relationship between the seizure or developmental outcome and brain myelination was investigated in patients with cryptogenic West syndrome. Subjects and Methods From 1999 to 2005, cranial magnetic resonance imaging examinations were performed in nine patients with West syndrome, to evaluate the development of myelination. All patients had been diagnosed to have cryptogenic West syndrome, and they had no gross structural brain lesions on magnetic resonance imaging. Symptomatic cases or patients with obvious underlying cerebral lesions were excluded from the study. Each patient fulfilled the criteria for the diagnosis of West syndrome: namely, the clinical appearance of infantile spasms, hypsarrhythmia on electroencephalogram (EEG), and arrest of psychomotor development. In these patients, a detailed clinical history was obtained including the age at onset, the seizure type, the stage of development at onset, the treatment, and the frequency of seizures and developmental status 2 years after onset. The developmental status was classified into three categories: normal development (developmental quotient DQ ⬎ 75), mild developmental delay (DQ ⫽ 74-50), and severe developmental delay (DQ ⬍ 50). Magnetic resonance imaging studies were performed using a 1.5-T Signa scanner (General Electric Medical Systems, Milwaukee, WI). Axial scans were obtained parallel to the orbitomeatal line with a slice thickness of 5 mm. All images were obtained using spin-echo pulse sequence (TR: 600 ms, TE: 35 ms, T1 weighted; TR: 2000 ms, TE: 100
Communications should be addressed to: Dr. Takano; Department of Pediatrics; Shiga University of Medical Science; Seta-Tsukinowa, Otsu 520-2192, Japan. E-mail: [email protected] Received April 3, 2007; accepted June 27, 2007.
Takano et al: Myelination in West Syndrome 417
ms, T2 weighted). Fluid attenuated inversion recovery (FLAIR) images were also analyzed (TI: 2200 ms, TR: 10,002 ms, TE: 142 ms), to detect more subtle brain lesions. Based on the standard development of brain myelination under magnetic resonance imaging determined in previous studies [7,8], signal intensities were examined at 13 different brain segments: middle cerebellar peduncle, crus cerebri, internal capsule posterior limb, internal capsule anterior limb, corpus callosum splenium, corpus callosum genu, centrum semiovale, occipital central white matter, frontal central white matter, temporal central white matter, occipital peripheral white matter, frontal peripheral white matter, and temporal peripheral white matter. Hyperintense and hypointense areas, relative to the gray matter, were assessed to be myelinated white matter in a T1-weighted image and a T2-weighted image, respectively. Myelination was considered to be delayed if it occurred at least 2 months late, according to the standards established by Barkovich et al. [9] under T1-weighted or T2-weighted imaging. All magnetic resonance imaging were performed within 1 month of onset of West syndrome and before treatment with adrenocorticotropic hormone therapy (0.4 IU/kg once every day for 2 weeks, once every other day for 2 weeks, and twice weekly for 2 weeks). All images were retrospectively analyzed by at least two of the authors, including pediatric neurologists.
and one by ZNS (zonisamide) (case 6). In each case, these anticonvulsants became effective by the 3rd week after the first administration. The seizures of all patients were controlled for 2 years after onset. The developmental outcome was normal in six cases (cases 1, 2, 4, 5, 6, and 9); the other three cases showed a mild developmental delay (cases 3, 7, and 8) at 2 years after onset. A comparison of the normal development of myelination together with the age limits revealed delayed myelination in three cases under T1-weighted imaging (cases 3, 4, and 7) (Fig 1) and two cases under T2-weighted imaging (cases 4 and 8) (Fig 2). The correlation between seizure outcome or developmental status 2 years after onset and delayed myelination at the onset of West syndrome was examined. Neither seizure outcome (P ⫽ 1.000) nor developmental status (P ⫽ 0.047) was positively correlated with the existence of delayed myelination.
Results
Discussion
The clinical histories of the nine patients with West syndrome are summarized in Table 1. The time of onset of spasms ranged from 4 to 11 months. The main types of spasms were brief axial movements in flexion or extension of neck or limbs. Two cases showed only upward gazing. All patients had normal development prior to the first spasms. Spasms were controlled in all patients: six cases were controlled by adrenocorticotropic hormone (cases 1, 2, 3, 7, 8, and 9), two by VPA (valproate) (cases 4 and 5),
Myelin deposition is a crucial process during brain maturation. A positive correlation has been observed between the progress of myelination and psychomotor development, suggesting that myelination demonstrates the functional maturity of the brain [10]. In West syndrome, the most important factor determining developmental outcome is whether the patient is classified as cryptogenic-idiopathic or as symptomatic. The percentage of patients with a normal developmental outcome ranged
Table 1.
Clinical and demographic characteristics of nine patients with cryptogenic West syndrome
Case
Sex
Age at Onset, mo
1 2
M F
4 6
3 4 5 6
M F M F
6 6 6 7
7
M
9
8
F
10
9
F
11
Delayed Myelination T1 T2
Treatment*
Extension of four limbs Extension of upper limbs; flexion of neck and lower limbs Flexion of upper limbs; upward gazing Flexion of neck and four limbs Upward gazing Flexion of neck and lower limbs; extension of upper limbs Flexion of neck; extension of four limbs Flexion of neck and four limbs; upward gazing Upward gazing
VB6, VPA, ZNS, ACTH VB6, VPA, ACTH
Normal Normal
⫺ ⫺
⫺ ⫺
VB6, VPA, ZNS, ACTH VB6, VPA VB6, VPA ZNS
Mild delay Normal Normal Normal
⫹ ⫹ ⫺ ⫺
⫺ ⫹ ⫺ ⫺
VPA, ACTH
Mild delay
⫹
⫺
VPA, VB6, ACTH
Mild delay
⫺
⫹
VPA, VB6, ACTH
Normal
⫺
⫺
Abbreviations: ACTH ⫽ Adrenocorticotropic hormone F ⫽ Female M ⫽ Male T1, T2 ⫽ T1-weighted, T2-weighted VB6 ⫽ Pyridoxine VPA ⫽ Valproate ZNS ⫽ Zonisamide ⫹, ⫺ ⫽ Positive (yes), negative (no) * Bold italic type highlights the most effective anticonvulsant in each case. † In all cases, seizure status 2 years after onset was controlled.
418
Developmental Status, 2 years after Onset†
Spasms
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Vol. 37 No. 6
Figure 1. Myelination under T1-weighted magnetic resonance imaging, showing the standard line of normal myelination together with age limits. Numbers on closed circles are case numbers. Cases 3, 4, and 7 are located below the standard line, revealing myelination delayed by at least 2 months. Abbreviations: C Semi ⫽ centrum semiovale; CC: g ⫽ corpus callosum genu; CC: sp ⫽ corpus callosum splenium; Cr S ⫽ crus cerebri; FWM: c ⫽ frontal central white matter; FWM: p ⫽ frontal peripheral white matter; IC: ant ⫽ internal capsule anterior limb; IC: pos ⫽ internal capsule posterior limb; MCP ⫽ middle cerebellar peduncle; OWM: c ⫽ occipital central white matter; OWM: p ⫽ occipital peripheral white matter; TWM: c ⫽ temporal central white matter; and TWM: p ⫽ temporal peripheral white matter.
from 5% to 19% among the symptomatic cases, and from 30% to 70% among the cryptogenic cases [11]. Delayed myelination is more frequently observed in patients with symptomatic West syndrome than in those with idiopathic West syndrome. In the cryptogenic cases, the delay of myelination tends to increase during the course of this syndrome, at least in children with a poor clinical outcome [6]. Cortical hypometabolism, detected by positron emission tomography scans, has also been suggested to be positively correlated with delayed myelination at 10 months of age [12]. These investigations indicate that identifying the myelination status at the onset of West syndrome is important for accurately evaluating the prognosis of this disease— especially because there are no gross structural brain abnormalities in this group. Maturation of the cortical, physiological, and morphological properties of the nervous system, including myelination is closely related to epileptogenesis. Abnormalities
in myelin development have been related to the age of onset of infantile spasms in association with the maximal maturational changes of dendritic synapses and mitotic activities at that time [13]. The maturation of neocortical pyramidal neurons and the thalamocortical system may also be related to the ability to produce the high voltage cortical activity underlying hypsarrhythmia [14]. Despite these investigations, there is still no direct evidence of a causal relationship between epileptic spasms and delayed myelination. Various factors have been studied to evaluate the prognosis of West syndrome [15]. Early factors associated with a good prognosis include the mild nature of psychomotor regression, the persistence of spindles on electroencephalograms recorded during non-rapid eye movement sleep, and a prompt improvement in the clinical status and electroencephalography recordings in response to treatment [15]. Unfavorable factors include severe
Figure 2. Myelination under T2-weighted magnetic resonance imaging, showing the standard line of normal myelination together with age limits. Numbers on closed circles are case numbers. Cases 4 and 8 are located below the standard line, revealing myelination delayed by at least 2 months. Abbreviations are as given for Figure 1.
Takano et al: Myelination in West Syndrome 419
regression, focalized electroencephalographic abnormalities, failure of development to resume promptly after the initiation of therapy, the recurrence of spasms, onset before 5 months or after 1 year of age, and hypsarrhythmia associated with a discontinuation of treatment [15]. A delay in the initiation of treatment is associated with an adverse cognitive outcome, only in cryptogenic cases [16]. In symptomatic cases, it appears that the myelination pattern is related to the psychomotor retardation but not to the severity of seizures in West syndrome [3]. The persistence of chaotic activity on the electroencephalogram is seen primarily in cases with severe developmental delay [2]. Myelination is one of the most important factors influencing brain maturation and epileptogenesis. In the present study, however, neither the seizure outcome nor the developmental status positively correlated with the existence of delayed myelination at the onset of cryptogenic West syndrome.
References [1] Commission on Pediatric Epilepsy of the International League Against Epilepsy. Workshop on infantile spasms. Epilepsia 1992;33:195. [2] Saltik S, Kocer N, Dervent A. Magnetic resonance imaging findings in infantile spasms: etiologic and pathophysiologic aspects. J Child Neurol 2003;18:241-6. [3] Muroi J, Okuno T, Kuno C, et al. An MRI study of the myelination pattern in West syndrome. Brain Dev 1996;18:179-84. [4] Plouin P, Jalin C, Dulac O, et al. Enregistrement ambulatoire de
420
PEDIATRIC NEUROLOGY
Vol. 37 No. 6
I’EEG pendant 24 heures dans les spasms infantiles epileptiques. Rev Electroencephalogr Neurophysiol Clin 1987;17:309-18. [5] Kasai K, Watanabe K, Negoro T, et al. Delayed myelination in West syndrome. Psychiatry Clin Neurosci 1995;49:S256-6. [6] Schropp C, Staudt M, Staudt F, et al. Delayed myelination in children with West syndrome: an MRI-study. Neuropediatrics 1994;25: 116-20. [7] Kizildag B, Dusunceli E, Fitoz S, Erden I. The role of classic spin echo and FLAIR sequences for the evaluation of myelination in MR imaging. Diagn Interv Radiol 2005;11:130-6. [8] Barkovich AJ. Normal development of the neonatal and infant brain, skull, and spine. In: Barkovich AJ. Pediatric neuroimaging, 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2005:17-75. [9] Barkovich AJ. Concepts of myelin and myelination in neuroradiology. Am J Neuroradiol 2000;21:1099-109. [10] Van der Knaap MS, Valk J, Bakker CJ, et al. Myelination as an expression of the functional maturity of the brain. Dev Med Child Neurol 1991;33:849-57. [11] Cowan LD, Hudson LS. The epidemiology and natural history of infantile spasms. J Child Neurol 1991;6:355-64. [12] Natsume J, Watanabe K, Maeda N, et al. Cortical hypometabolism and delayed myelination in West syndrome. Epilepsia 1996;37: 1180-4. [13] Riikonen R. Infantile spasms: some new theoretical aspects. Epilepsia 1983;24:159-68. [14] Avanzini G, Sancini G, Canafoglia L, Franceschetti S. Maturation of cortical physiological properties relevant to epileptogenesis. In: Avanzini G, Spreafico R, Andermann F, editors. Abnormal cortical development and epilepsy: from basic to clinica science. London: John Libbey, 1999:63-75. [15] Watanabe K. West syndrome: etiological and prognostic aspects. Brain Dev 1998;20:1-8. [16] Koo B, Hwang PA, Logan WJ. Infantile spasms: outcome and prognostic factors of cryptogenic and symptomatic groups. Neurology 1993;43:2322-7.
Introduction West syndrome is characterized by infantile spasms, hypsarrhythmia, and intellectual disability. This syndrome is classified within two etiologic groups, as symptomatic and cryptogenic, in the International Classification of Epilepsies and Epileptic Syndromes [1]. The cryptogenic group does not present any observable underlying cerebral lesion, whereas the symptomatic group has pre-existing brain damage. The most common pre-existing brain abnormalities that are visualized by magnetic resonance imaging are a thinning of the corpus callosum, dilatation of the cerebral ventricles, delayed myelination, lesions of diencephalic deep gray matter, and an enlargement of the subarachnoid space [2]. However, delayed myelination appears to be independent of any specific etiology, and it
From Department of Pediatrics, Shiga University of Medical Science, Seta-Tsukinowa, Otsu 520-2192, Japan.
© 2007 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2007.06.021 ● 0887-8994/07/$—see front matter
is sometimes difficult to assess in the absence of neuropathological investigations [3]. Idiopathic West syndrome has been previously reported to occur in a normal child; the hypsarrhythmic pattern is typical and symmetric, and it reappears between individual spasms during clusters [4]. Even in idiopathic West syndrome, which is expected to be a more benign outcome, delayed myelination has been observed in about half of all patients [5]. In children with cryptogenic West syndrome and with tuberous sclerosis, myelination has been reported to be either normal or only mildly delayed in the first month after the onset of the spasms, but delayed myelination seems to increase in the course of the West syndrome [6]. To evaluate the prognostic value of delayed myelination at onset, the relationship between the seizure or developmental outcome and brain myelination was investigated in patients with cryptogenic West syndrome. Subjects and Methods From 1999 to 2005, cranial magnetic resonance imaging examinations were performed in nine patients with West syndrome, to evaluate the development of myelination. All patients had been diagnosed to have cryptogenic West syndrome, and they had no gross structural brain lesions on magnetic resonance imaging. Symptomatic cases or patients with obvious underlying cerebral lesions were excluded from the study. Each patient fulfilled the criteria for the diagnosis of West syndrome: namely, the clinical appearance of infantile spasms, hypsarrhythmia on electroencephalogram (EEG), and arrest of psychomotor development. In these patients, a detailed clinical history was obtained including the age at onset, the seizure type, the stage of development at onset, the treatment, and the frequency of seizures and developmental status 2 years after onset. The developmental status was classified into three categories: normal development (developmental quotient DQ ⬎ 75), mild developmental delay (DQ ⫽ 74-50), and severe developmental delay (DQ ⬍ 50). Magnetic resonance imaging studies were performed using a 1.5-T Signa scanner (General Electric Medical Systems, Milwaukee, WI). Axial scans were obtained parallel to the orbitomeatal line with a slice thickness of 5 mm. All images were obtained using spin-echo pulse sequence (TR: 600 ms, TE: 35 ms, T1 weighted; TR: 2000 ms, TE: 100
Communications should be addressed to: Dr. Takano; Department of Pediatrics; Shiga University of Medical Science; Seta-Tsukinowa, Otsu 520-2192, Japan. E-mail: [email protected] Received April 3, 2007; accepted June 27, 2007.
Takano et al: Myelination in West Syndrome 417
ms, T2 weighted). Fluid attenuated inversion recovery (FLAIR) images were also analyzed (TI: 2200 ms, TR: 10,002 ms, TE: 142 ms), to detect more subtle brain lesions. Based on the standard development of brain myelination under magnetic resonance imaging determined in previous studies [7,8], signal intensities were examined at 13 different brain segments: middle cerebellar peduncle, crus cerebri, internal capsule posterior limb, internal capsule anterior limb, corpus callosum splenium, corpus callosum genu, centrum semiovale, occipital central white matter, frontal central white matter, temporal central white matter, occipital peripheral white matter, frontal peripheral white matter, and temporal peripheral white matter. Hyperintense and hypointense areas, relative to the gray matter, were assessed to be myelinated white matter in a T1-weighted image and a T2-weighted image, respectively. Myelination was considered to be delayed if it occurred at least 2 months late, according to the standards established by Barkovich et al. [9] under T1-weighted or T2-weighted imaging. All magnetic resonance imaging were performed within 1 month of onset of West syndrome and before treatment with adrenocorticotropic hormone therapy (0.4 IU/kg once every day for 2 weeks, once every other day for 2 weeks, and twice weekly for 2 weeks). All images were retrospectively analyzed by at least two of the authors, including pediatric neurologists.
and one by ZNS (zonisamide) (case 6). In each case, these anticonvulsants became effective by the 3rd week after the first administration. The seizures of all patients were controlled for 2 years after onset. The developmental outcome was normal in six cases (cases 1, 2, 4, 5, 6, and 9); the other three cases showed a mild developmental delay (cases 3, 7, and 8) at 2 years after onset. A comparison of the normal development of myelination together with the age limits revealed delayed myelination in three cases under T1-weighted imaging (cases 3, 4, and 7) (Fig 1) and two cases under T2-weighted imaging (cases 4 and 8) (Fig 2). The correlation between seizure outcome or developmental status 2 years after onset and delayed myelination at the onset of West syndrome was examined. Neither seizure outcome (P ⫽ 1.000) nor developmental status (P ⫽ 0.047) was positively correlated with the existence of delayed myelination.
Results
Discussion
The clinical histories of the nine patients with West syndrome are summarized in Table 1. The time of onset of spasms ranged from 4 to 11 months. The main types of spasms were brief axial movements in flexion or extension of neck or limbs. Two cases showed only upward gazing. All patients had normal development prior to the first spasms. Spasms were controlled in all patients: six cases were controlled by adrenocorticotropic hormone (cases 1, 2, 3, 7, 8, and 9), two by VPA (valproate) (cases 4 and 5),
Myelin deposition is a crucial process during brain maturation. A positive correlation has been observed between the progress of myelination and psychomotor development, suggesting that myelination demonstrates the functional maturity of the brain [10]. In West syndrome, the most important factor determining developmental outcome is whether the patient is classified as cryptogenic-idiopathic or as symptomatic. The percentage of patients with a normal developmental outcome ranged
Table 1.
Clinical and demographic characteristics of nine patients with cryptogenic West syndrome
Case
Sex
Age at Onset, mo
1 2
M F
4 6
3 4 5 6
M F M F
6 6 6 7
7
M
9
8
F
10
9
F
11
Delayed Myelination T1 T2
Treatment*
Extension of four limbs Extension of upper limbs; flexion of neck and lower limbs Flexion of upper limbs; upward gazing Flexion of neck and four limbs Upward gazing Flexion of neck and lower limbs; extension of upper limbs Flexion of neck; extension of four limbs Flexion of neck and four limbs; upward gazing Upward gazing
VB6, VPA, ZNS, ACTH VB6, VPA, ACTH
Normal Normal
⫺ ⫺
⫺ ⫺
VB6, VPA, ZNS, ACTH VB6, VPA VB6, VPA ZNS
Mild delay Normal Normal Normal
⫹ ⫹ ⫺ ⫺
⫺ ⫹ ⫺ ⫺
VPA, ACTH
Mild delay
⫹
⫺
VPA, VB6, ACTH
Mild delay
⫺
⫹
VPA, VB6, ACTH
Normal
⫺
⫺
Abbreviations: ACTH ⫽ Adrenocorticotropic hormone F ⫽ Female M ⫽ Male T1, T2 ⫽ T1-weighted, T2-weighted VB6 ⫽ Pyridoxine VPA ⫽ Valproate ZNS ⫽ Zonisamide ⫹, ⫺ ⫽ Positive (yes), negative (no) * Bold italic type highlights the most effective anticonvulsant in each case. † In all cases, seizure status 2 years after onset was controlled.
418
Developmental Status, 2 years after Onset†
Spasms
PEDIATRIC NEUROLOGY
Vol. 37 No. 6
Figure 1. Myelination under T1-weighted magnetic resonance imaging, showing the standard line of normal myelination together with age limits. Numbers on closed circles are case numbers. Cases 3, 4, and 7 are located below the standard line, revealing myelination delayed by at least 2 months. Abbreviations: C Semi ⫽ centrum semiovale; CC: g ⫽ corpus callosum genu; CC: sp ⫽ corpus callosum splenium; Cr S ⫽ crus cerebri; FWM: c ⫽ frontal central white matter; FWM: p ⫽ frontal peripheral white matter; IC: ant ⫽ internal capsule anterior limb; IC: pos ⫽ internal capsule posterior limb; MCP ⫽ middle cerebellar peduncle; OWM: c ⫽ occipital central white matter; OWM: p ⫽ occipital peripheral white matter; TWM: c ⫽ temporal central white matter; and TWM: p ⫽ temporal peripheral white matter.
from 5% to 19% among the symptomatic cases, and from 30% to 70% among the cryptogenic cases [11]. Delayed myelination is more frequently observed in patients with symptomatic West syndrome than in those with idiopathic West syndrome. In the cryptogenic cases, the delay of myelination tends to increase during the course of this syndrome, at least in children with a poor clinical outcome [6]. Cortical hypometabolism, detected by positron emission tomography scans, has also been suggested to be positively correlated with delayed myelination at 10 months of age [12]. These investigations indicate that identifying the myelination status at the onset of West syndrome is important for accurately evaluating the prognosis of this disease— especially because there are no gross structural brain abnormalities in this group. Maturation of the cortical, physiological, and morphological properties of the nervous system, including myelination is closely related to epileptogenesis. Abnormalities
in myelin development have been related to the age of onset of infantile spasms in association with the maximal maturational changes of dendritic synapses and mitotic activities at that time [13]. The maturation of neocortical pyramidal neurons and the thalamocortical system may also be related to the ability to produce the high voltage cortical activity underlying hypsarrhythmia [14]. Despite these investigations, there is still no direct evidence of a causal relationship between epileptic spasms and delayed myelination. Various factors have been studied to evaluate the prognosis of West syndrome [15]. Early factors associated with a good prognosis include the mild nature of psychomotor regression, the persistence of spindles on electroencephalograms recorded during non-rapid eye movement sleep, and a prompt improvement in the clinical status and electroencephalography recordings in response to treatment [15]. Unfavorable factors include severe
Figure 2. Myelination under T2-weighted magnetic resonance imaging, showing the standard line of normal myelination together with age limits. Numbers on closed circles are case numbers. Cases 4 and 8 are located below the standard line, revealing myelination delayed by at least 2 months. Abbreviations are as given for Figure 1.
Takano et al: Myelination in West Syndrome 419
regression, focalized electroencephalographic abnormalities, failure of development to resume promptly after the initiation of therapy, the recurrence of spasms, onset before 5 months or after 1 year of age, and hypsarrhythmia associated with a discontinuation of treatment [15]. A delay in the initiation of treatment is associated with an adverse cognitive outcome, only in cryptogenic cases [16]. In symptomatic cases, it appears that the myelination pattern is related to the psychomotor retardation but not to the severity of seizures in West syndrome [3]. The persistence of chaotic activity on the electroencephalogram is seen primarily in cases with severe developmental delay [2]. Myelination is one of the most important factors influencing brain maturation and epileptogenesis. In the present study, however, neither the seizure outcome nor the developmental status positively correlated with the existence of delayed myelination at the onset of cryptogenic West syndrome.
References [1] Commission on Pediatric Epilepsy of the International League Against Epilepsy. Workshop on infantile spasms. Epilepsia 1992;33:195. [2] Saltik S, Kocer N, Dervent A. Magnetic resonance imaging findings in infantile spasms: etiologic and pathophysiologic aspects. J Child Neurol 2003;18:241-6. [3] Muroi J, Okuno T, Kuno C, et al. An MRI study of the myelination pattern in West syndrome. Brain Dev 1996;18:179-84. [4] Plouin P, Jalin C, Dulac O, et al. Enregistrement ambulatoire de
420
PEDIATRIC NEUROLOGY
Vol. 37 No. 6
I’EEG pendant 24 heures dans les spasms infantiles epileptiques. Rev Electroencephalogr Neurophysiol Clin 1987;17:309-18. [5] Kasai K, Watanabe K, Negoro T, et al. Delayed myelination in West syndrome. Psychiatry Clin Neurosci 1995;49:S256-6. [6] Schropp C, Staudt M, Staudt F, et al. Delayed myelination in children with West syndrome: an MRI-study. Neuropediatrics 1994;25: 116-20. [7] Kizildag B, Dusunceli E, Fitoz S, Erden I. The role of classic spin echo and FLAIR sequences for the evaluation of myelination in MR imaging. Diagn Interv Radiol 2005;11:130-6. [8] Barkovich AJ. Normal development of the neonatal and infant brain, skull, and spine. In: Barkovich AJ. Pediatric neuroimaging, 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2005:17-75. [9] Barkovich AJ. Concepts of myelin and myelination in neuroradiology. Am J Neuroradiol 2000;21:1099-109. [10] Van der Knaap MS, Valk J, Bakker CJ, et al. Myelination as an expression of the functional maturity of the brain. Dev Med Child Neurol 1991;33:849-57. [11] Cowan LD, Hudson LS. The epidemiology and natural history of infantile spasms. J Child Neurol 1991;6:355-64. [12] Natsume J, Watanabe K, Maeda N, et al. Cortical hypometabolism and delayed myelination in West syndrome. Epilepsia 1996;37: 1180-4. [13] Riikonen R. Infantile spasms: some new theoretical aspects. Epilepsia 1983;24:159-68. [14] Avanzini G, Sancini G, Canafoglia L, Franceschetti S. Maturation of cortical physiological properties relevant to epileptogenesis. In: Avanzini G, Spreafico R, Andermann F, editors. Abnormal cortical development and epilepsy: from basic to clinica science. London: John Libbey, 1999:63-75. [15] Watanabe K. West syndrome: etiological and prognostic aspects. Brain Dev 1998;20:1-8. [16] Koo B, Hwang PA, Logan WJ. Infantile spasms: outcome and prognostic factors of cryptogenic and symptomatic groups. Neurology 1993;43:2322-7.