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Adult-onset leukoencephalopathy with vanishing white matter
European Journal of Radiology Extra 46 (2003) 90 /92 http://intl.elsevierhealth.com/journals/ejrx
Adult-onset leukoencephalopathy with vanishing white matter Masaru Matsui a,*, Kotaro Mizutani b, Yukio Miki c, Takahiro Mezaki a, Yuu Takahashi d, Hiroshi Shibasaki a a
Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan b Department of Neurology, Sakakibara Hakuho Hospital, 5630 Sakakibaracho, Hisai 514-1251, Japan c Department of Nuclear Medicine and Diagnostic Imaging, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan d Department of Neurology, Ise General Hospital, 3038 Kusube-cho, Ise 516-0014, Japan Received 30 July 2002; received in revised form 16 September 2002; accepted 18 September 2002
Abstract Leukoencephalopathy with vanishing white matter is a new disease entity with characteristic features of MRI. This disease usually occurs in children and is thought to be rare, particularly in the non-Caucasian population. We present an adult-onset Japanese case of leukoencephalopathy with vanishing white matter. MRI findings in this case included linear high signal intensity on T2-weighted and fluid-attenuated inversion recovery images in the pons in addition to typical abnormalities in the cerebral white matter. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Leukoencephalopathy; Vanishing white matter; MRI; Ataxia; Spasticity
1. Introduction
2. Case report
Leukoencephalopathy with vanishing white matter (VWM) was recently defined as an autosomal recessive disorder characterized by chronic progressive cerebellar ataxia, spasticity and unique MRI findings [1 /3]. This disease is also referred to as childhood ataxia with diffuse central hypomyelination (CACH) [4]. VWM was initially thought to occur only in childhood [1,2,4], but adolescent-onset cases and a young adult in a presymptomatic state have also been reported [3]. Prass et al. [5] recently reported the first case of a VWM patient with onset in late adulthood who had presented with mild dementia, and they proposed that VWM should be considered in any demented adult patients associated with extensive white matter lesions. We here describe an adult-onset Japanese case of VWM. To our knowledge, this is the first report of an adult VWM patient of Asian origin.
The patient was a 47-year-old female. She developed slowly progressive gait disturbance and hand clumsiness at the age of 42. Neurological examination showed cerebellar ataxia and exaggerated deep tendon reflexes in all extremities with bilateral Babinski sign. She could not walk independently. There was no sensory loss or visual loss. The Mini-Mental State Examination score was 26 of 30, although she had no complaint of mental slowness. The family history was negative for similar disease. She was married and had four healthy children. Her parents were not related. Laboratory studies were normal, including routine blood screening, adrenal and thyroid function tests, amino acid analysis, the levels of very long chain fatty acids, and the activities of lysosomal enzymes (arylsulfatase A, a-glucosidase, bglucosidase, a-galactosidase, b-galactosidase and b-hexosaminidase). Routine cerebrospinal fluid (CSF) analyses were normal. Glycine in the CSF was not examined in our case, although van der Knaap et al. reported a moderate elevation of CSF glycine in VWM [6]. Brain MRI showed symmetric and diffuse abnormal signals in the cerebral white matter (Fig. 1a/c). The abnormal
* Corresponding author. Tel.: /81-75-751-3768; fax: /81-75-7619780 E-mail address: [email protected] (M. Matsui).
1571-4675/03/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S1571-4675(03)00054-3
M. Matsui et al. / European Journal of Radiology Extra 46 (2003) 90 /92
91
Fig. 1. Axial T1-weighted (SE, TR/TE /500/20) (a), T2-weighted (FSE, TR/TE /5000/88) (b, f) and FLAIR (TR/TI/TE /6900/1700/110) (c), and sagittal FLAIR (TR/TI/TE /6900/1700/110) (d) and T1-weighted (SE, TR/TE /500/20) (e) images obtained at 0.5 T. Cerebral white matter was symmetrically and diffusely abnormal (a, b, c). Within the abnormal white matter, a dotlike pattern was visible on axial images (a, c) and a radiating pattern on sagittal images (d). Corpus callosum atrophy was noted (arrows) (e). A linear high signal was identified bilaterally in the pontine tegmentum (arrows), and the cerebellar white matter was mildly hyperintense (f).
white matter in parts had a signal intensity close to that of CSF on all pulse sequences. In areas of CSF-like white matter, a dotlike pattern was found on axial images (Fig. 1a, c) and a radiating pattern on sagittal images (Fig. 1d). The corpus callosum was atrophic (Fig. 1e). In the pons, a linear high signal was identified bilaterally on T2-weighted (Fig. 1f) and fluid-attenuated inversion recovery (FLAIR) images. The signal intensity
of the cerebellar white matter was mildly increased on T2-weighted (Fig. 1f) and FLAIR images.
3. Discussion VWM was initially defined radiologically among unclassified cases of leukoencephalopathies [1]. The
92
M. Matsui et al. / European Journal of Radiology Extra 46 (2003) 90 /92
Fig. 1 (Continued)
MRI features of VWM [2,3] are as follows: (1) the cerebral white matter is symmetrically and diffusely abnormal; (2) part or all of the abnormal white matter has a signal intensity close to that of CSF on all pulse sequences including FLAIR sequence; (3) within the areas of CSF-like white matter, a dotlike pattern is seen on axial images and a radiating pattern on sagittal images. The present patient had all these findings and fulfilled the diagnostic criteria for VWM [3]. Van der Knaap et al. [2,3] reported that the brainstem can be affected in VWM. The involvement of the pontine corticospinal tracts, central tegmental tracts and/or transverse pontine fibers was demonstrated by MRI in some cases of VWM [2,3,7]. In our case, a linear high signal on T2-weighted and FLAIR images was clearly identified bilaterally in the pontine tegmentum, which may correspond to myelin loss in the ventral trigeminothalamic tracts pathologically described by van der Knaap et al. [2]. The clinical features of our patient were very similar to those reported in previous cases of VWM. Furthermore, she had typical MRI abnormalities such as a dotlike pattern and a radiating pattern in the cerebral white matter. Our case suggested that VWM should be considered in the differential diagnosis of adult-onset leukoencephalopathy even though there is no complaint of mental decline.
References [1] Hanefeld F, Holzbach U, Kruse B, Wilichowski E, Christen HJ, Frahm J. Diffuse white matter disease in three children: an encephalopathy with unique features on magnetic resonance imaging and proton magnetic resonance spectroscopy. Neuropediatrics 1993;24:244 /8. [2] van der Knaap MS, Barth PG, Gabree¨ls FJM, Franzoni E, Begeer JH, Stroink H, Rotteveel JJ, Valk J. A new leukoencephalopathy with vanishing white matter. Neurology 1997;48:845 /55. [3] van der Knaap MS, Kamphorst W, Barth PG, Kraaijeveld CL, Gut E, Valk J. Phenotypic variation in leukoencephalopathy with vanishing white matter. Neurology 1998;51:540 /7. [4] Schiffmann R, Moller JR, Trapp BD, Shih HHL, Farrer RG, Katz DA, Alger JR, Parker CC, Hauer PE, Kaneski CR, Heiss JD, Kaye EM, Quarles RH, Brady RO, Barton NW. Childhood ataxia with diffuse central nervous system hypomyelination. Ann Neurol 1994;35:331 /40. [5] Prass K, Bru¨ck W, Schro¨der NWJ, Bender A, Prass M, Wolf T, van der Knaap MS, Zschenderlein R. Adult-onset leukoencephalopathy with vanishing white matter presenting with dementia. Ann Neurol 2001;50:665 /8. [6] van der Knaap MS, Wevers RA, Kure S, Gabreels FJ, Verhoeven NM, van Raaij-Selten B, Jaeken J. Increased cerebrospinal fluid glycine: a biochemical marker for a leukoencephalopathy with vanishing white matter. J Child Neurol 1999;14:728 /31. [7] Francalanci P, Eymard-Pierre E, Dionisi-Vici C, Boldrini R, Piemonte F, Virgili R, Fariello G, Bosman C, Santorelli FM, Boespflug-Tanguy O, Bertini E. Fatal infantile leukodystrophy: a severe variant of CACH/VWM syndrome, allelic to chromosome 3q27. Neurology 2001;57:265 /70.
Adult-onset leukoencephalopathy with vanishing white matter Masaru Matsui a,*, Kotaro Mizutani b, Yukio Miki c, Takahiro Mezaki a, Yuu Takahashi d, Hiroshi Shibasaki a a
Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan b Department of Neurology, Sakakibara Hakuho Hospital, 5630 Sakakibaracho, Hisai 514-1251, Japan c Department of Nuclear Medicine and Diagnostic Imaging, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan d Department of Neurology, Ise General Hospital, 3038 Kusube-cho, Ise 516-0014, Japan Received 30 July 2002; received in revised form 16 September 2002; accepted 18 September 2002
Abstract Leukoencephalopathy with vanishing white matter is a new disease entity with characteristic features of MRI. This disease usually occurs in children and is thought to be rare, particularly in the non-Caucasian population. We present an adult-onset Japanese case of leukoencephalopathy with vanishing white matter. MRI findings in this case included linear high signal intensity on T2-weighted and fluid-attenuated inversion recovery images in the pons in addition to typical abnormalities in the cerebral white matter. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Leukoencephalopathy; Vanishing white matter; MRI; Ataxia; Spasticity
1. Introduction
2. Case report
Leukoencephalopathy with vanishing white matter (VWM) was recently defined as an autosomal recessive disorder characterized by chronic progressive cerebellar ataxia, spasticity and unique MRI findings [1 /3]. This disease is also referred to as childhood ataxia with diffuse central hypomyelination (CACH) [4]. VWM was initially thought to occur only in childhood [1,2,4], but adolescent-onset cases and a young adult in a presymptomatic state have also been reported [3]. Prass et al. [5] recently reported the first case of a VWM patient with onset in late adulthood who had presented with mild dementia, and they proposed that VWM should be considered in any demented adult patients associated with extensive white matter lesions. We here describe an adult-onset Japanese case of VWM. To our knowledge, this is the first report of an adult VWM patient of Asian origin.
The patient was a 47-year-old female. She developed slowly progressive gait disturbance and hand clumsiness at the age of 42. Neurological examination showed cerebellar ataxia and exaggerated deep tendon reflexes in all extremities with bilateral Babinski sign. She could not walk independently. There was no sensory loss or visual loss. The Mini-Mental State Examination score was 26 of 30, although she had no complaint of mental slowness. The family history was negative for similar disease. She was married and had four healthy children. Her parents were not related. Laboratory studies were normal, including routine blood screening, adrenal and thyroid function tests, amino acid analysis, the levels of very long chain fatty acids, and the activities of lysosomal enzymes (arylsulfatase A, a-glucosidase, bglucosidase, a-galactosidase, b-galactosidase and b-hexosaminidase). Routine cerebrospinal fluid (CSF) analyses were normal. Glycine in the CSF was not examined in our case, although van der Knaap et al. reported a moderate elevation of CSF glycine in VWM [6]. Brain MRI showed symmetric and diffuse abnormal signals in the cerebral white matter (Fig. 1a/c). The abnormal
* Corresponding author. Tel.: /81-75-751-3768; fax: /81-75-7619780 E-mail address: [email protected] (M. Matsui).
1571-4675/03/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S1571-4675(03)00054-3
M. Matsui et al. / European Journal of Radiology Extra 46 (2003) 90 /92
91
Fig. 1. Axial T1-weighted (SE, TR/TE /500/20) (a), T2-weighted (FSE, TR/TE /5000/88) (b, f) and FLAIR (TR/TI/TE /6900/1700/110) (c), and sagittal FLAIR (TR/TI/TE /6900/1700/110) (d) and T1-weighted (SE, TR/TE /500/20) (e) images obtained at 0.5 T. Cerebral white matter was symmetrically and diffusely abnormal (a, b, c). Within the abnormal white matter, a dotlike pattern was visible on axial images (a, c) and a radiating pattern on sagittal images (d). Corpus callosum atrophy was noted (arrows) (e). A linear high signal was identified bilaterally in the pontine tegmentum (arrows), and the cerebellar white matter was mildly hyperintense (f).
white matter in parts had a signal intensity close to that of CSF on all pulse sequences. In areas of CSF-like white matter, a dotlike pattern was found on axial images (Fig. 1a, c) and a radiating pattern on sagittal images (Fig. 1d). The corpus callosum was atrophic (Fig. 1e). In the pons, a linear high signal was identified bilaterally on T2-weighted (Fig. 1f) and fluid-attenuated inversion recovery (FLAIR) images. The signal intensity
of the cerebellar white matter was mildly increased on T2-weighted (Fig. 1f) and FLAIR images.
3. Discussion VWM was initially defined radiologically among unclassified cases of leukoencephalopathies [1]. The
92
M. Matsui et al. / European Journal of Radiology Extra 46 (2003) 90 /92
Fig. 1 (Continued)
MRI features of VWM [2,3] are as follows: (1) the cerebral white matter is symmetrically and diffusely abnormal; (2) part or all of the abnormal white matter has a signal intensity close to that of CSF on all pulse sequences including FLAIR sequence; (3) within the areas of CSF-like white matter, a dotlike pattern is seen on axial images and a radiating pattern on sagittal images. The present patient had all these findings and fulfilled the diagnostic criteria for VWM [3]. Van der Knaap et al. [2,3] reported that the brainstem can be affected in VWM. The involvement of the pontine corticospinal tracts, central tegmental tracts and/or transverse pontine fibers was demonstrated by MRI in some cases of VWM [2,3,7]. In our case, a linear high signal on T2-weighted and FLAIR images was clearly identified bilaterally in the pontine tegmentum, which may correspond to myelin loss in the ventral trigeminothalamic tracts pathologically described by van der Knaap et al. [2]. The clinical features of our patient were very similar to those reported in previous cases of VWM. Furthermore, she had typical MRI abnormalities such as a dotlike pattern and a radiating pattern in the cerebral white matter. Our case suggested that VWM should be considered in the differential diagnosis of adult-onset leukoencephalopathy even though there is no complaint of mental decline.
References [1] Hanefeld F, Holzbach U, Kruse B, Wilichowski E, Christen HJ, Frahm J. Diffuse white matter disease in three children: an encephalopathy with unique features on magnetic resonance imaging and proton magnetic resonance spectroscopy. Neuropediatrics 1993;24:244 /8. [2] van der Knaap MS, Barth PG, Gabree¨ls FJM, Franzoni E, Begeer JH, Stroink H, Rotteveel JJ, Valk J. A new leukoencephalopathy with vanishing white matter. Neurology 1997;48:845 /55. [3] van der Knaap MS, Kamphorst W, Barth PG, Kraaijeveld CL, Gut E, Valk J. Phenotypic variation in leukoencephalopathy with vanishing white matter. Neurology 1998;51:540 /7. [4] Schiffmann R, Moller JR, Trapp BD, Shih HHL, Farrer RG, Katz DA, Alger JR, Parker CC, Hauer PE, Kaneski CR, Heiss JD, Kaye EM, Quarles RH, Brady RO, Barton NW. Childhood ataxia with diffuse central nervous system hypomyelination. Ann Neurol 1994;35:331 /40. [5] Prass K, Bru¨ck W, Schro¨der NWJ, Bender A, Prass M, Wolf T, van der Knaap MS, Zschenderlein R. Adult-onset leukoencephalopathy with vanishing white matter presenting with dementia. Ann Neurol 2001;50:665 /8. [6] van der Knaap MS, Wevers RA, Kure S, Gabreels FJ, Verhoeven NM, van Raaij-Selten B, Jaeken J. Increased cerebrospinal fluid glycine: a biochemical marker for a leukoencephalopathy with vanishing white matter. J Child Neurol 1999;14:728 /31. [7] Francalanci P, Eymard-Pierre E, Dionisi-Vici C, Boldrini R, Piemonte F, Virgili R, Fariello G, Bosman C, Santorelli FM, Boespflug-Tanguy O, Bertini E. Fatal infantile leukodystrophy: a severe variant of CACH/VWM syndrome, allelic to chromosome 3q27. Neurology 2001;57:265 /70.