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Congenital muscular dystrophy (Fukuyama type) — Changes in the white matter low density on CT
Congenital Muscular Dystrophy (Fukuyama Type) -Changes in the White Matter Low Density on CT Mieko Yoshioka, MD and Shigeo Saiwai, MD
Sixty-two computed tomographic (CT) scans of 36 patients with congenital muscular dystrophy of Fukuyama type (FCMD) were analysed A low density area in the cerebral white matter was characteristic of FCMD and a special reference was made to the changes in the white matter low density. It was present in 15 patients out of 36 (42%) andfrequently seen in the scans obtained on the younger patients; among 11 scans taken ofpatients between 1 and 2 years of age, 10 scans (91%) showed the white matter low density. Repeated cr scans were carried out on 26 of the 36 cases. Follow-up study revealed Nzat the white matter low density areas were most apparent around the age of one year and decreased or disappeared at 2 or 3 years of age. From these observations, delayed myelination was suspected for the pathogenesis of the low density area found in FCMD. Key words: Computed tomographic scans, congenital muscular dystrophy (Fukuyama type), low density area in the white matter, delayed myelination. Yoshioka M, Saiwai S. Congenital muscular dystrophy (Fukuyama type) - changes in the white matter low density on CT. Brain Dev 1988; 1 0: 41-4
The Fukuyama type of congenital muscular dystrophy (FCMD) is one of three major forms of congenital muscular dystrophy (CMD) [1], and is particularly prevalent in Japan. It is associated with early-onset hypotonia, facial muscle involvement, joint contractures, and severe mental retardation [2]. FCMD is characterized by the coexistence of a congenital degenerative disorder of muscle with a developmental defect of the central nervous system [2]. The major changes in the central nervous system represent an arrest in the migration and differentiation of neurons early in the course of fetal development [3]. This defect is expressed as microcephaly, poly microgyria, pachygyria, lissencephaly, and heterotopias [4]. The etiology of FCMD remains unclear. A genetic factor may be important [5], but some authors have suggested an infectious etiology [6-9]. Recent studies using cranial computed tomography (CT) scans [10] have revealed dilated ventricles, cortical atrophy and a low
From the Departments of Pediatrics (MY) and Radiology (SS), Kobe General Hospital, Kobe. Received for publication: August 4, 1987. Accepted for publication: October 12, 1987. Correspondence address: Dr. M. Yoshioka, Department of Pediatrics, Kobe General Hospital, 4·6, Minatojima-Nakamachi, Chuo·ku, Kobe 650, Japan.,
density area in the cerebral white matter. The latter finding is not uncommonly seen in several forms of CMD, but is especially characteristic of FCMD. At autopsy there was no conclusive evidence on the white matter change of FCMD. We have followed the cranial CT scans in patients with FCMD in hopes of clarifying the nature of the white matter change on CT and acquiring useful data on the pathogenesis of FCMD.
MATERIALS AND METHODS Thirty-six patients with FCMD were studied. There were 16 males and 20 females ranging in age from 17 days to 19 years 5 months, with an average age of 6 years. The diagnosis of these patients was established according to the standard criteria [2]. Detailed clinical and laboratory data on 25 out of these 36 cases have been published previously [10]. Follow-up CT scans were obtained in 26 patients with the interval ranging from two weeks to 33 months, and an average interval of 19 months. Twentyone patients were examined twice, five patients over three times. In all, 62 cranial CT scans were analysed in this study. All patients were examined with an EMI 1010 scanner (120 KV, 10 mm slice thickness) or a General Electric CT / T 8800 high resolution body scanner (120 KV, 10 mm slice thickness).
Case
number 1 32
~
6 7 8
9
10 11
12
13
14 15 16
_ ......
0
~ •
•
~
o
• a scan with low density areas
0
o a scan without low density areas
0 -----...0-----•
•
----.0 0>----0
17
18 19
20
21
22 23 74
25
C>-----<)
o
0
26
27 28 29 30 31 32 33 34 35
~
0------0
~
o
o
o
36L-__~____~__~____- r____~__~____~____r-~.~;==!.
10
6
12
14
16
Age at CT examination
18
____
(in years)
Fig 1 Individual follow-up of patients with FCMD who had or had not a low density area in the white matter on CT. Each horizontal line represents one case. The symbols along each line indicate the CT scan of the patient with or without low density areas at the time of a follow-up study.
Fig 2 Left: the scans of a l-year-old girl with FCMD. A diffuse, low density area is evident in the deep white matter. There is moderate dilatation of the lateral ventricle, especially posteriorly ( colpocephalic). Right: repeat scans at age 2 years. The low density area in the white matter is diminished, especially in the occipitoparietallobe.
RESULTS A low density area in the white matter was present in 15 patients out of 36 (42%). Individual follow-up of patients on CT is shown in Fig 1. The low density areas in the white matter were present frequently in the scans obtained on the younger patients. Among 11 scans taken of patients between 1 and 2 years of age, 10 scans (91 %) showed the white matter low density areas, while 25 scans of patients between 6 and 17 years of age did not
42 Brain & Developmenr, VallO, No 1, 1988
reveal these changes. Two scans obtained in a patient over 17 years of age showed white matter low density areas. This patient had been examined twice and no difference was found in the low density area between these two scans. Repeat CT scans were carried out on 26 of the 36 cases. On the repeat scans, the white matter low density areas found in 14 of the 26 patients at the first examination decreased or disappeared in 8, increased in 2, and
Fig 3 cr scans obtained at 1 year of age (left) and at 3 years 1 month of age (right) in a female with FCMD. Disappearance of the low density area was observed in the latter scan. In addition, dilatation of lateral ventricles is slightly decreased.
Fig 4 CT scans at ages 1 7 days, 7 months, 1 year 2 months and 2 years in a female with FCMD (from left to right). The low density area in the white matter was not visible on the first scan, but appeared in the second scan. It was most prominent in the third scan; some reduction was observed in the last scan. There was moderate dilatation of the lateral ventricle, especially posteriorly (colpocephaly) and smooth subsurface lamination was apparent in the left temporoparietal lobe in the third scan. Slight progress of dilatation of lateral ventricles was also seen.
were unchanged in 2. Two cases showed an increase followed by a decrease in the low density areas. In 8 cases with decrease or disappearance of the low density areas, the first scans were obtained when the patient was about 1 year old and the repeat scans were taken when the patient was over 2 years old (Figs 2, 3). An increase in the low density areas was observed in two cases, who were examined first at around 6 months of age and then at around 1 year of age. Two cases showed no change in the low density areas. In these cases, the first scans were obtained when the patient was over 3 years 6 months of age. Several scans were taken in two patients
during infancy. In these cases, the low density areas were obscure in the first scans, but became apparent when the patient was I year old; the areas then decreased when the patient was around 2 years old (Fig 4).
DISCUSSION This study of follow-up scans in patients with FCMD reveals that the white matter low density areas change as the patient's age increases. The low density areas in the white matter are most apparent when the patient is around the age of one year and decrease or disappear
Yoshioka and Saiwai: CT changes in congenital muscular dystrophy 43
when the patient reaches 2 or 3 years of age. After this, the scans remain unchanged. These observations suggest that the white matter low density areas on CT scans in patients with FCMD is different from those seen in patients with demyelinating (normal myelin formation with subsequent destruction) or dysmyelinating (abnormal formation or maintenance of myelin due to an enzymatic disturbance) disorders [11]. Delayed myelination is the most likely explanation for the change found in FCMD. In previous autopsy studies of FCMD [3,4], the white matter change has not been striking. A mild gliosis or edema in the cerebral white matter or myelin pallor in the centrum semiovale has sometimes been reported, but most cases show no remarkable abnormalities in the cerebral white matter. In most cases, the age at autopsy was over five years. On the other hand, hypomyelination in the cerebrum was noted in one case autopsied at the age of 11 months. A study of lipid composition of the cerebral gray and white matter in a lO-year-old female with FCMD [12] revealed the lipid abnormality was restricted to gangliosides in the gray matter of the brain. The water and lipid content of the cerebral white matter were nearly normal compared to those in the patients with Duchenne muscular dystrophy and the normal control. The periventricular low density areas of FCMD should not be confused with the transependymal resorption of cerebrospinal fluid (TRCSF) found in patients with hydrocephalus [13]. TRCSF produces lucent zones centered anterior to the frontal horns with confluence in the' corpus callosum; these lucent zones extend medially to the trigones and occipital horns. The frontallucencies of FCMD, on the other hand, seldom extend into the genu of the corpus callosum and spare the medial subependymal regions along the trigones and occipital horns. In addition, the low density areas in the white matter found in FCMD disappear from the occipital to the frontal lobe (Fig 2), which is comparable to normal development of myelination [14]. Further pathological studies, especially autopsy studies of brains in cases below one year of age, will be necessary to get pertinent data on the pathogenesis of delayed myelination found in FCMD.
44 Brain & Development, Vol 1 0, No 1, 1988
ACKNOWLEDGMENTS This study was supported by Grant No 86-03 from the National Center for Nervous, Mental and Muscular Disorders (NCNMMD) of the Ministry of Health and Welfare, Japan.
REFERENCES 1. Banker BQ. Congenital muscular dystrophy. In: Engel AG, Banker BQ, eds. Myology. Vol 2. New York: McGraw Hill, 1986;1367-82. 2. Fukuyama Y, Haruna H, Kawazura M. A peculiar form of congenital progressive muscular dystrophy. Paediatr Univ Tokyo (Tokyo) 1960;4:5-8. 3. Takada K, Nakamura H, Tanaka J. Cortical dysplasia in congenital muscular dystrophy with central nervous system involvement (Fukuyama type). J Neuropathol Exp Neurol 1984;43:395-407. 4. Kamoshita S, Konishi Y, Segawa M, Fukuyama Y. Congenital muscular dystrophy as a disease of the central nervous system. Arch Neurol 1976;33:513-6. 5. Fukuyama Y, Ohsawa M. A genetic study of the Fukuyama type congenital muscular dystrophy. Brain Dev (Tokyo) 1984;6:373-90, 6. Misugi N. Light and electron microscopic studies of congenital muscular dystrophy. Brain Dev (Tokyo) 1980;2: 191-9. 7. Kinoshita M, Iwasaki Y, Wada F. A case of congenital polymyositis-a possible pathogenesis of Fukuyama type congenital muscular dystrophy. Rinsho Shinkeigaku (Tokyo) 1980;20:911-6. 8. Olney R, Miller R. Inflammatory infiltration in Fukuyama type congenital muscular dystrophy. Muscle Nerve 1983; 6:75-6. 9. Kohrman MH, Picchietti DL, Wollmann R, Chelmicka-Schorr EW. A variant of Fukuyama congenital muscular dystrophy in a non-Japanese child. Pediatr Neurol 1986;2:290-3. 10. Yoshioka M, Okuno T, Honda Y, Nakano Y. Central nervous system involvement in progressive muscular dystrophy. Arch Dis Child 1980;55:589-94. 11. Heinz ER, Drayer BP, Haenggeli CA, Painter MJ, Crumrine P. Computed tomography in white-matter disease. Radiology 1979;130:371-8. 12. Eda I, Takashima S, Ohno K, Takeshita K. Lipid composition of the cerebral gray and white matter in a case with Fukuyama type congenital muscular dystrophy. Brain Dev (Tokyo) 1985;7:523-5. 13. Lotz PR, Ballinger WE, Quisling RG. Subcortical arteriosclerotic encephalopathy: cr spectrum and pathologic correlation. AJN 1986;7:817-22. 14. Johnson MA, Pennock JM, Bydder GM, et al. Clinical NMR imaging of the brain in children: normal and neurologic disease. AJN 1983;4: 1013-26.
Sixty-two computed tomographic (CT) scans of 36 patients with congenital muscular dystrophy of Fukuyama type (FCMD) were analysed A low density area in the cerebral white matter was characteristic of FCMD and a special reference was made to the changes in the white matter low density. It was present in 15 patients out of 36 (42%) andfrequently seen in the scans obtained on the younger patients; among 11 scans taken ofpatients between 1 and 2 years of age, 10 scans (91%) showed the white matter low density. Repeated cr scans were carried out on 26 of the 36 cases. Follow-up study revealed Nzat the white matter low density areas were most apparent around the age of one year and decreased or disappeared at 2 or 3 years of age. From these observations, delayed myelination was suspected for the pathogenesis of the low density area found in FCMD. Key words: Computed tomographic scans, congenital muscular dystrophy (Fukuyama type), low density area in the white matter, delayed myelination. Yoshioka M, Saiwai S. Congenital muscular dystrophy (Fukuyama type) - changes in the white matter low density on CT. Brain Dev 1988; 1 0: 41-4
The Fukuyama type of congenital muscular dystrophy (FCMD) is one of three major forms of congenital muscular dystrophy (CMD) [1], and is particularly prevalent in Japan. It is associated with early-onset hypotonia, facial muscle involvement, joint contractures, and severe mental retardation [2]. FCMD is characterized by the coexistence of a congenital degenerative disorder of muscle with a developmental defect of the central nervous system [2]. The major changes in the central nervous system represent an arrest in the migration and differentiation of neurons early in the course of fetal development [3]. This defect is expressed as microcephaly, poly microgyria, pachygyria, lissencephaly, and heterotopias [4]. The etiology of FCMD remains unclear. A genetic factor may be important [5], but some authors have suggested an infectious etiology [6-9]. Recent studies using cranial computed tomography (CT) scans [10] have revealed dilated ventricles, cortical atrophy and a low
From the Departments of Pediatrics (MY) and Radiology (SS), Kobe General Hospital, Kobe. Received for publication: August 4, 1987. Accepted for publication: October 12, 1987. Correspondence address: Dr. M. Yoshioka, Department of Pediatrics, Kobe General Hospital, 4·6, Minatojima-Nakamachi, Chuo·ku, Kobe 650, Japan.,
density area in the cerebral white matter. The latter finding is not uncommonly seen in several forms of CMD, but is especially characteristic of FCMD. At autopsy there was no conclusive evidence on the white matter change of FCMD. We have followed the cranial CT scans in patients with FCMD in hopes of clarifying the nature of the white matter change on CT and acquiring useful data on the pathogenesis of FCMD.
MATERIALS AND METHODS Thirty-six patients with FCMD were studied. There were 16 males and 20 females ranging in age from 17 days to 19 years 5 months, with an average age of 6 years. The diagnosis of these patients was established according to the standard criteria [2]. Detailed clinical and laboratory data on 25 out of these 36 cases have been published previously [10]. Follow-up CT scans were obtained in 26 patients with the interval ranging from two weeks to 33 months, and an average interval of 19 months. Twentyone patients were examined twice, five patients over three times. In all, 62 cranial CT scans were analysed in this study. All patients were examined with an EMI 1010 scanner (120 KV, 10 mm slice thickness) or a General Electric CT / T 8800 high resolution body scanner (120 KV, 10 mm slice thickness).
Case
number 1 32
~
6 7 8
9
10 11
12
13
14 15 16
_ ......
0
~ •
•
~
o
• a scan with low density areas
0
o a scan without low density areas
0 -----...0-----•
•
----.0 0>----0
17
18 19
20
21
22 23 74
25
C>-----<)
o
0
26
27 28 29 30 31 32 33 34 35
~
0------0
~
o
o
o
36L-__~____~__~____- r____~__~____~____r-~.~;==!.
10
6
12
14
16
Age at CT examination
18
____
(in years)
Fig 1 Individual follow-up of patients with FCMD who had or had not a low density area in the white matter on CT. Each horizontal line represents one case. The symbols along each line indicate the CT scan of the patient with or without low density areas at the time of a follow-up study.
Fig 2 Left: the scans of a l-year-old girl with FCMD. A diffuse, low density area is evident in the deep white matter. There is moderate dilatation of the lateral ventricle, especially posteriorly ( colpocephalic). Right: repeat scans at age 2 years. The low density area in the white matter is diminished, especially in the occipitoparietallobe.
RESULTS A low density area in the white matter was present in 15 patients out of 36 (42%). Individual follow-up of patients on CT is shown in Fig 1. The low density areas in the white matter were present frequently in the scans obtained on the younger patients. Among 11 scans taken of patients between 1 and 2 years of age, 10 scans (91 %) showed the white matter low density areas, while 25 scans of patients between 6 and 17 years of age did not
42 Brain & Developmenr, VallO, No 1, 1988
reveal these changes. Two scans obtained in a patient over 17 years of age showed white matter low density areas. This patient had been examined twice and no difference was found in the low density area between these two scans. Repeat CT scans were carried out on 26 of the 36 cases. On the repeat scans, the white matter low density areas found in 14 of the 26 patients at the first examination decreased or disappeared in 8, increased in 2, and
Fig 3 cr scans obtained at 1 year of age (left) and at 3 years 1 month of age (right) in a female with FCMD. Disappearance of the low density area was observed in the latter scan. In addition, dilatation of lateral ventricles is slightly decreased.
Fig 4 CT scans at ages 1 7 days, 7 months, 1 year 2 months and 2 years in a female with FCMD (from left to right). The low density area in the white matter was not visible on the first scan, but appeared in the second scan. It was most prominent in the third scan; some reduction was observed in the last scan. There was moderate dilatation of the lateral ventricle, especially posteriorly (colpocephaly) and smooth subsurface lamination was apparent in the left temporoparietal lobe in the third scan. Slight progress of dilatation of lateral ventricles was also seen.
were unchanged in 2. Two cases showed an increase followed by a decrease in the low density areas. In 8 cases with decrease or disappearance of the low density areas, the first scans were obtained when the patient was about 1 year old and the repeat scans were taken when the patient was over 2 years old (Figs 2, 3). An increase in the low density areas was observed in two cases, who were examined first at around 6 months of age and then at around 1 year of age. Two cases showed no change in the low density areas. In these cases, the first scans were obtained when the patient was over 3 years 6 months of age. Several scans were taken in two patients
during infancy. In these cases, the low density areas were obscure in the first scans, but became apparent when the patient was I year old; the areas then decreased when the patient was around 2 years old (Fig 4).
DISCUSSION This study of follow-up scans in patients with FCMD reveals that the white matter low density areas change as the patient's age increases. The low density areas in the white matter are most apparent when the patient is around the age of one year and decrease or disappear
Yoshioka and Saiwai: CT changes in congenital muscular dystrophy 43
when the patient reaches 2 or 3 years of age. After this, the scans remain unchanged. These observations suggest that the white matter low density areas on CT scans in patients with FCMD is different from those seen in patients with demyelinating (normal myelin formation with subsequent destruction) or dysmyelinating (abnormal formation or maintenance of myelin due to an enzymatic disturbance) disorders [11]. Delayed myelination is the most likely explanation for the change found in FCMD. In previous autopsy studies of FCMD [3,4], the white matter change has not been striking. A mild gliosis or edema in the cerebral white matter or myelin pallor in the centrum semiovale has sometimes been reported, but most cases show no remarkable abnormalities in the cerebral white matter. In most cases, the age at autopsy was over five years. On the other hand, hypomyelination in the cerebrum was noted in one case autopsied at the age of 11 months. A study of lipid composition of the cerebral gray and white matter in a lO-year-old female with FCMD [12] revealed the lipid abnormality was restricted to gangliosides in the gray matter of the brain. The water and lipid content of the cerebral white matter were nearly normal compared to those in the patients with Duchenne muscular dystrophy and the normal control. The periventricular low density areas of FCMD should not be confused with the transependymal resorption of cerebrospinal fluid (TRCSF) found in patients with hydrocephalus [13]. TRCSF produces lucent zones centered anterior to the frontal horns with confluence in the' corpus callosum; these lucent zones extend medially to the trigones and occipital horns. The frontallucencies of FCMD, on the other hand, seldom extend into the genu of the corpus callosum and spare the medial subependymal regions along the trigones and occipital horns. In addition, the low density areas in the white matter found in FCMD disappear from the occipital to the frontal lobe (Fig 2), which is comparable to normal development of myelination [14]. Further pathological studies, especially autopsy studies of brains in cases below one year of age, will be necessary to get pertinent data on the pathogenesis of delayed myelination found in FCMD.
44 Brain & Development, Vol 1 0, No 1, 1988
ACKNOWLEDGMENTS This study was supported by Grant No 86-03 from the National Center for Nervous, Mental and Muscular Disorders (NCNMMD) of the Ministry of Health and Welfare, Japan.
REFERENCES 1. Banker BQ. Congenital muscular dystrophy. In: Engel AG, Banker BQ, eds. Myology. Vol 2. New York: McGraw Hill, 1986;1367-82. 2. Fukuyama Y, Haruna H, Kawazura M. A peculiar form of congenital progressive muscular dystrophy. Paediatr Univ Tokyo (Tokyo) 1960;4:5-8. 3. Takada K, Nakamura H, Tanaka J. Cortical dysplasia in congenital muscular dystrophy with central nervous system involvement (Fukuyama type). J Neuropathol Exp Neurol 1984;43:395-407. 4. Kamoshita S, Konishi Y, Segawa M, Fukuyama Y. Congenital muscular dystrophy as a disease of the central nervous system. Arch Neurol 1976;33:513-6. 5. Fukuyama Y, Ohsawa M. A genetic study of the Fukuyama type congenital muscular dystrophy. Brain Dev (Tokyo) 1984;6:373-90, 6. Misugi N. Light and electron microscopic studies of congenital muscular dystrophy. Brain Dev (Tokyo) 1980;2: 191-9. 7. Kinoshita M, Iwasaki Y, Wada F. A case of congenital polymyositis-a possible pathogenesis of Fukuyama type congenital muscular dystrophy. Rinsho Shinkeigaku (Tokyo) 1980;20:911-6. 8. Olney R, Miller R. Inflammatory infiltration in Fukuyama type congenital muscular dystrophy. Muscle Nerve 1983; 6:75-6. 9. Kohrman MH, Picchietti DL, Wollmann R, Chelmicka-Schorr EW. A variant of Fukuyama congenital muscular dystrophy in a non-Japanese child. Pediatr Neurol 1986;2:290-3. 10. Yoshioka M, Okuno T, Honda Y, Nakano Y. Central nervous system involvement in progressive muscular dystrophy. Arch Dis Child 1980;55:589-94. 11. Heinz ER, Drayer BP, Haenggeli CA, Painter MJ, Crumrine P. Computed tomography in white-matter disease. Radiology 1979;130:371-8. 12. Eda I, Takashima S, Ohno K, Takeshita K. Lipid composition of the cerebral gray and white matter in a case with Fukuyama type congenital muscular dystrophy. Brain Dev (Tokyo) 1985;7:523-5. 13. Lotz PR, Ballinger WE, Quisling RG. Subcortical arteriosclerotic encephalopathy: cr spectrum and pathologic correlation. AJN 1986;7:817-22. 14. Johnson MA, Pennock JM, Bydder GM, et al. Clinical NMR imaging of the brain in children: normal and neurologic disease. AJN 1983;4: 1013-26.