Comparison of MRI White Matter Changes with Neuropsychologic Impairment in Cockayne Syndrome Katsuo Sugita, MD, Jun-ichi Takanashi, MD, Mitsuko Ishii, MD, and Hiroo Niimi,
MD
The neuropsychologic function and white matter changes observed on magnetic resonance imaging (MRI) in Cockayne syndrome were studied. MRI with Tz-weighted sequences revealed periventricular hyperintensity and white matter hyperintensity in all 3 Cockayne syndrome patients examined; in contrast, 8 age-matched controls had no periventricular or white matter hyperintensity. MRI scans were graded according to the severity of periventricular or white matter hyperintensity using a scale applied to an elderly patient population. There was no difference in the severity of MRI white matter changes in these 3 Cockayne syndrome patients, 2 of whom had severe neuropsychologic functions and one a relatively milder one. There was no correlation between neuropsychologic impairment and MRI white matter changes. Sugita K, Takanashi J, Ishii M, Niimi H. Comparison of MRI white matter changes with neuropsychologic impairment in Cockayne syndrome. Pediatr Neurol 1992;s: 295-s.
Introduction Cockayne syndrome (CS) is one of the dysmyelinating disorders and has clinical features of premature aging and mental deterioration, in addition to microcephaly, ataxia, intracranial calcification, cachectic dwarfism, pigmentary abnormalities of the retina (i.e., retinitis pigmentosa), sen-
From the Department of Pediatrics; Chiba University School of Medicine; l-8-l Inohana, Chuuou-ku; Chiba 280, Japan.
sorineural deafness, and photosensitivity [ 1,2]. Dysmyelinating or demyelinating disorders in CS exhibit periventricular hyperintensity (PVH) or white matter hyperintensity (WMH) on magnetic resonance imaging (MRI) with Tz-weighted sequences [3,4] that are frequently observed in elderly people [5-71; however, there have been no conclusive data on the correlation between the neuropsychologic function and MRI white matter lesions in CS patients. In this study, we compared the former with the latter in 3 CS patients with mild to severe neurodegeneration. Methods farienr
1. This
13-year-old
female was born after a normal pregnanand has been described previously[8]. History was unremarkable until age 3 years when she exhibited resting tremor in both hands. On examination at age 5 years, she already had a characteristic face with a beak-like nose and other typical features consistent with CS. CT, performed at the age of 6 years, revealed bilateral basal ganglia calcification and cerebellar atrophy. At present, she can still walk without support, although her gait is slightly broad-based and ataxic. Her mental status and language development are mildly retarded. Patients 2 and 3. These 8- and IO-year-old girls had healthy parents and have been described previously [9]. Psychomotor development was normal in both patients during the first year of life, but delayed acquirement of motor milestones became evident thereafter. When examined at our hospital at ages 3 and 4 years, respectively, they had several clinical manifestations typical of CS. CT, performed at the ages of 4 and 5 years, respectively, revealed calciticadon of the basal ganglia as well as of the subcortical white matter. Their motor and intellectual development regressed gradually and now they are spastic and do not walk independently. Eight children (4 males, 4 females), ages 6-15 years (mean age: 10.6 years), were used as normal controls and also examined by MRI and compared with the 3 CS patients. These children were referred for nonneurologic problems or nonspecific neurologic complaints, such as headache or a single seizure. They were free of any neurologic, psychiatric, or major systemic illnesses. MRI. MRI was performed with a superconducting 0.5 T system (Picker International, Highland Heights, OH). All scans were obtained using a contiguous 10 mm multislice technique. The 3 CS patients and 8 controls were examined mainly by Tz-weighted spin-echo (SE) sequences (TR: 2,080 ms, TE: 80 ms), as reported previously [lo]. Axial MRI scans were interpreted using the Fazekas rating scale [5]; PVHs were graded as follows: 0 - Absence; I - “Caps” or pencil-thin lining; 2 - Smooth “halo;” and. 3 - Irregular PVH extending into the deep white matter. Independent deep WMH signals were rated as follows: 0 - Absence; I - Punctate foci; 2 - Beginning of confluence foci; and, 3 - Large confluent areas. Psychomotor Development Testing. We performedthe RevisedKForm Developmental Test [ll] which provides a Posture-Motor Developmental Quotient (PM-DQ), Cognition-Adaptation Developmental Quotient (CA-DQ), and Language-Social Developmental Quotient (I-S-
cy 8141 weeksgestation
Communications should be addressed to: Dr. Sugita; Department of Pediatrics; Chiba University School Medicine; 1-8-1 Inohana, Chuuou-ku; Chiba 280, Japan. Received December 30, 1991; accepted March 9, 1992.
Sugita et al: MRI in Cockayne
of
Syndrome 295
DQ). ment
According to this developmental was divided into motor or mental
test. neuropsychologic impairand was defined by none. mild.
moderate, or severe in the same way as previously reported [10,12] with slight modification. Severe motor or mental impairment was considered to be present in children with motor scores (PM-DQ) of < 50 or mental score (CA-DQ and LS-DQ) of < 50. Moderate impairment was diagnosed with motor or mental scores of 50-70. Children were classified as having mild impairments when motor or mental scores were 71-84. The remaining children were classified as having no functional impairment.
Results We performed MRI scans in 3 CS patients at almost the same time that neuropsychologic testing was performed. MRI with T2-weighted sequences revealed high signal lesions in the periventricular and subcortical white matter in all CS patients, in comparison to the complete absence of PVH or WMH in the 8 controls (Figs l-3). These findings and the neuropsychologic impairments of the patients are summarized in Table 1 and are discussed below. Discussion The clinical symptoms of our 3 patients coincided with the major criteria reported by Sugarman et al. [2]. Accord-
A
ing to Lowry’s classification [ 131, all 3 CS patients had the classic form and should be designated as CS type I. Patient 1 displayed the relatively uncommon features of late age at onset and a clinically milder form of CS, compared to Patients 2 and 3. CS patients, however, have demonstrated a wide range of clinical severity and some CS patients with clinically atypical features, including normal intelligence, have been reported [ 14,151. MRI is a sensitive tool for demonstrating white matter disease. The signal hyperintensity of the white matter on Tz-weighted MRI, previously reported in both types I and II of CS [3,4], was also observed in our 3 CS patients as PVH and WMH, but was not observed in normal agematched young children. PVH and WMH were regarded as evidence of diffuse white matter disease in CS, while Boltshauser et al. assumed that these MRI changes in CS reflected hypomyelination (dysmyelination) rather than demyelination [4]. On the basis of our MRI observations, it was not possible to separate secondary demyelination from primary dysmyelination. Our psychomotor developmental test results for CS failed to disclose a correlation between motor or mental impairment and PVH or WMH on MRI. Nowell et al. reported that MRI is not more sensitive than CT in detect-
B
Figure 2. (A.B) MRI. Patient 3: IO-year-old female wirh severe ps)~cl~ologicfiotcrio,ts. Sin~ilarjhdings as found in Figures IA, IB.
296
PEDIATRIC
NEUROLOGY
Vol. 8 No. 4
neuro-
ing childhood demyelinating or dysmyelinating diseases, although it is more sensitive than CT in detecting the degree of disease present [ 161. On MRI, PVH is often observed in various childhood diseases and conditions, such as obstructive and normal pressure hydrocephalus, multiple sclerosis, and radiation necrosis; its incidence in asymptomatic individuals increases with age [ 171. Conversely, there has been no conclusive data on the correlation of white matter lesions on MRI, especially PVH or WMH, and the later neurologic handicap in low-birthweight infants [ 10,181. Further MRI investigation is needed to clarify the link between the changes in the white matter and their clinical significance in children. It was of interest with respect to the aging process of the brain that cranial MRI findings in progerioid CS patients resembled those reported in the elderly [5-71. In the elderly, Hunt et al. reported that there was no correlation between the neuropsychologic function and the presence of PVH or WMH on MRI and concluded that only white matter changes were of doubtful clinical significance [6]. Recently, Leys et al. also reported a lack of correlation of MRI white matter and periventricular hyperintensity with age or mental status in the elderly [7]. Our results were Table 1. MRI findings patients and controls
and neuropsychologic
MRI Patient No./ Age (yrs)
Grade PVH
Grade WMH
test results
in CS
Neuropsychologic Impairment Motor Mental
CS Patients
l/l3
3
3
Moderate
Mild
218
3
3
Severe
Severe
3/10
3
3
Severe
Severe
0
0
None
None
Controls 5-12/6-I5 Abbreviations: PVH = Periventricular WMH = White matter
hyperintensity hyperintensity
consistent with those of the elderly, concluded by these authors, although it is still in question whether the MRI findings in the elderly can be applied to those of children. Neuropathologic studies of CS have demonstrated that the most constant findings are white matter and cerebeIlar atrophy with patchy demyelination and calcification in the basal ganglia with a variable degree of cerebral and cerebellar calcification [ 19-211. In demyelinating diseases the increase in water and the resultant PVH or WMH were said to result from the destruction of hydrophobic myelin. PVH or WMH, however, was also observed in normal elderly patients. Zimmerman et al. proposed the physiologic rather than the pathophysiologic explanation that PVH may be a reflection of the higher proportion of interstitial water at the ventricular lining resulting from concentric bulk flow within the white matter from the larger more peripheral site toward the more confined periventricular region in the normal elderly [ 171. Furthermore, marked variability in the intensity and extent of individual brain lesions has been observed in CS. This variability led different authors to stress different aspects of the neuropathologic picture. Crome and Kanjilal referred to the changes in their patients as “calcifying vasopathy of the brain” and considered the white matter changes to be angiopathy [21]. The diffuse white matter lesions observed on MRI in CS patients may potentially represent diffuse subcortical arteriosclerotic encephalopathy, which is usually observed in the elderly. These physiologic and pathologic similarities to aging brain may be one explanation for the lack of a link between neurologic impairment and MRI white matter changes in CS.
References [l] Coclcayne EA. Dwarfism with retinal atrophy and deafness. Arch Dis Child 1936;11:1-8. [2] Sugarman GI, Landing BH, Reed WB. Cockayne syndrome: Clinical study of two patients and neuropathologic findings in one. Clin Pediatr 1977;16:225-32. [3] Dabbagh 0. Swaiman KF. Cockayne syndrome: MRI correlates of hypomyelination. Pediatr Neurol 1988;4: 113-6. [4] Boltshauser E. Yalcinkaya C, Wichmann W, Reutter F, Prader A, Valavanis A. MIU in Cockayne syndrome type I. Neuroradiology 1989;3 I:2767.
Sugita et al: MRI in Cockayne
Syndrome
297
[5] Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJNR 1987;8:421-6. [6] Hunt AL, Orrison WW, Yeo RA, et al. Clinical significance of MRI white matter lesions in the elderly. Neurology 1989;39:1470-4. [7] Leys D, Soetaert G, Petit H, Fauquette A. Pruvo J-P, Steinling M. Periventricular and white matter magnetic resonance imaging hyperintensities do not differ between Alzheimer’s disease and normal aging, Arch Neurol 1990:47:524-7. [8] Suglta K, Takanashi J, Suzuki N. Niimi H. Comparison of cellular sensitivity to uv killing with neuropsychological impairment in Cockayne syndrome patients. Brain Dev 1991;13:163-6. [9] Suglta K, Iai M. Tamai K, Aihara M, Arima M. UV or x-ray sensitivity of cells from Cockayne syndrome. No To Hattatsu 1986;lS: 286-91. [lo] Suglta K, Takeuchi A, Iai M, Tanabe Y. Neurologic sequelae and MRI in low-birth weight patients. Pediatr Neurol 1989;5:365-9. [ll] Shimazu M. ed. Revised K-form developmental test. Nakanishi Press, Kyoto, 1985; 103-24. [12] Sugita K, Iai M, Inoue T, Ohta R. Normative data and the effect of correction for prematurity on test scores in the psychomotor development of extremely low birthweight infants. Brain Dev 1990;12: 334-8.
298
PEDIATRIC
NEUROLOGY
Vol. 8 No. 4
[13] Lowry RB. Early onset of Cockayne syndrome. Am J Med Genet 1982;13:209-IO. [I41 Kennedy RM, Rowe VD, Kepes JJ. Cockayne syndrome: An atypical case. Neurology 1980:30: 1268-72. [15] Lanning M, Simila S. Cockayne’s syndrome, report of a case with normal intelligence. Z Kinderheilkd 1970; 109:70-5. [16] Nowell MA, Grossman RI, Hackney DB, Zimmerman RA. Goldberg HI, Bilaniuk LT. MR imaging of white matter disease in children. AJNR 1988;9:503-9. [17] Zimmerman RD. Fleming CA, Lee BCP, Saiot-Louis LA, Deck MDF. Perivennicular hyperintensity as seen by magnetic resonance: Prevalence and significance. AJNR 19867: 13-20. [18] Lipper EG, Ross GS, Heier L. Nass R. Magnetic resonance imaging in children of very low birth weight with suspected brain abnormalities. J Pediatr 1988;113:1046-9. [19] Soffer D, Grotsky W, Rapin I, Suzuki K. Cockayne syndrome: Unusual neuropathological findings and review of the literature. Ann Neurol 1979;6:340-8. [20] Moosa A, Dubowitz V. Peripheral neuropathy in Cockayne’s syndrome. Arch Dis Child 1970;45:674-7. [21] Crome L, Kanjilal GC. Cockayne’s syndrome: Case report. J Neurol Neurosurg Psychiatry 1971;34: 171-S.
MD
The neuropsychologic function and white matter changes observed on magnetic resonance imaging (MRI) in Cockayne syndrome were studied. MRI with Tz-weighted sequences revealed periventricular hyperintensity and white matter hyperintensity in all 3 Cockayne syndrome patients examined; in contrast, 8 age-matched controls had no periventricular or white matter hyperintensity. MRI scans were graded according to the severity of periventricular or white matter hyperintensity using a scale applied to an elderly patient population. There was no difference in the severity of MRI white matter changes in these 3 Cockayne syndrome patients, 2 of whom had severe neuropsychologic functions and one a relatively milder one. There was no correlation between neuropsychologic impairment and MRI white matter changes. Sugita K, Takanashi J, Ishii M, Niimi H. Comparison of MRI white matter changes with neuropsychologic impairment in Cockayne syndrome. Pediatr Neurol 1992;s: 295-s.
Introduction Cockayne syndrome (CS) is one of the dysmyelinating disorders and has clinical features of premature aging and mental deterioration, in addition to microcephaly, ataxia, intracranial calcification, cachectic dwarfism, pigmentary abnormalities of the retina (i.e., retinitis pigmentosa), sen-
From the Department of Pediatrics; Chiba University School of Medicine; l-8-l Inohana, Chuuou-ku; Chiba 280, Japan.
sorineural deafness, and photosensitivity [ 1,2]. Dysmyelinating or demyelinating disorders in CS exhibit periventricular hyperintensity (PVH) or white matter hyperintensity (WMH) on magnetic resonance imaging (MRI) with Tz-weighted sequences [3,4] that are frequently observed in elderly people [5-71; however, there have been no conclusive data on the correlation between the neuropsychologic function and MRI white matter lesions in CS patients. In this study, we compared the former with the latter in 3 CS patients with mild to severe neurodegeneration. Methods farienr
1. This
13-year-old
female was born after a normal pregnanand has been described previously[8]. History was unremarkable until age 3 years when she exhibited resting tremor in both hands. On examination at age 5 years, she already had a characteristic face with a beak-like nose and other typical features consistent with CS. CT, performed at the age of 6 years, revealed bilateral basal ganglia calcification and cerebellar atrophy. At present, she can still walk without support, although her gait is slightly broad-based and ataxic. Her mental status and language development are mildly retarded. Patients 2 and 3. These 8- and IO-year-old girls had healthy parents and have been described previously [9]. Psychomotor development was normal in both patients during the first year of life, but delayed acquirement of motor milestones became evident thereafter. When examined at our hospital at ages 3 and 4 years, respectively, they had several clinical manifestations typical of CS. CT, performed at the ages of 4 and 5 years, respectively, revealed calciticadon of the basal ganglia as well as of the subcortical white matter. Their motor and intellectual development regressed gradually and now they are spastic and do not walk independently. Eight children (4 males, 4 females), ages 6-15 years (mean age: 10.6 years), were used as normal controls and also examined by MRI and compared with the 3 CS patients. These children were referred for nonneurologic problems or nonspecific neurologic complaints, such as headache or a single seizure. They were free of any neurologic, psychiatric, or major systemic illnesses. MRI. MRI was performed with a superconducting 0.5 T system (Picker International, Highland Heights, OH). All scans were obtained using a contiguous 10 mm multislice technique. The 3 CS patients and 8 controls were examined mainly by Tz-weighted spin-echo (SE) sequences (TR: 2,080 ms, TE: 80 ms), as reported previously [lo]. Axial MRI scans were interpreted using the Fazekas rating scale [5]; PVHs were graded as follows: 0 - Absence; I - “Caps” or pencil-thin lining; 2 - Smooth “halo;” and. 3 - Irregular PVH extending into the deep white matter. Independent deep WMH signals were rated as follows: 0 - Absence; I - Punctate foci; 2 - Beginning of confluence foci; and, 3 - Large confluent areas. Psychomotor Development Testing. We performedthe RevisedKForm Developmental Test [ll] which provides a Posture-Motor Developmental Quotient (PM-DQ), Cognition-Adaptation Developmental Quotient (CA-DQ), and Language-Social Developmental Quotient (I-S-
cy 8141 weeksgestation
Communications should be addressed to: Dr. Sugita; Department of Pediatrics; Chiba University School Medicine; 1-8-1 Inohana, Chuuou-ku; Chiba 280, Japan. Received December 30, 1991; accepted March 9, 1992.
Sugita et al: MRI in Cockayne
of
Syndrome 295
DQ). ment
According to this developmental was divided into motor or mental
test. neuropsychologic impairand was defined by none. mild.
moderate, or severe in the same way as previously reported [10,12] with slight modification. Severe motor or mental impairment was considered to be present in children with motor scores (PM-DQ) of < 50 or mental score (CA-DQ and LS-DQ) of < 50. Moderate impairment was diagnosed with motor or mental scores of 50-70. Children were classified as having mild impairments when motor or mental scores were 71-84. The remaining children were classified as having no functional impairment.
Results We performed MRI scans in 3 CS patients at almost the same time that neuropsychologic testing was performed. MRI with T2-weighted sequences revealed high signal lesions in the periventricular and subcortical white matter in all CS patients, in comparison to the complete absence of PVH or WMH in the 8 controls (Figs l-3). These findings and the neuropsychologic impairments of the patients are summarized in Table 1 and are discussed below. Discussion The clinical symptoms of our 3 patients coincided with the major criteria reported by Sugarman et al. [2]. Accord-
A
ing to Lowry’s classification [ 131, all 3 CS patients had the classic form and should be designated as CS type I. Patient 1 displayed the relatively uncommon features of late age at onset and a clinically milder form of CS, compared to Patients 2 and 3. CS patients, however, have demonstrated a wide range of clinical severity and some CS patients with clinically atypical features, including normal intelligence, have been reported [ 14,151. MRI is a sensitive tool for demonstrating white matter disease. The signal hyperintensity of the white matter on Tz-weighted MRI, previously reported in both types I and II of CS [3,4], was also observed in our 3 CS patients as PVH and WMH, but was not observed in normal agematched young children. PVH and WMH were regarded as evidence of diffuse white matter disease in CS, while Boltshauser et al. assumed that these MRI changes in CS reflected hypomyelination (dysmyelination) rather than demyelination [4]. On the basis of our MRI observations, it was not possible to separate secondary demyelination from primary dysmyelination. Our psychomotor developmental test results for CS failed to disclose a correlation between motor or mental impairment and PVH or WMH on MRI. Nowell et al. reported that MRI is not more sensitive than CT in detect-
B
Figure 2. (A.B) MRI. Patient 3: IO-year-old female wirh severe ps)~cl~ologicfiotcrio,ts. Sin~ilarjhdings as found in Figures IA, IB.
296
PEDIATRIC
NEUROLOGY
Vol. 8 No. 4
neuro-
ing childhood demyelinating or dysmyelinating diseases, although it is more sensitive than CT in detecting the degree of disease present [ 161. On MRI, PVH is often observed in various childhood diseases and conditions, such as obstructive and normal pressure hydrocephalus, multiple sclerosis, and radiation necrosis; its incidence in asymptomatic individuals increases with age [ 171. Conversely, there has been no conclusive data on the correlation of white matter lesions on MRI, especially PVH or WMH, and the later neurologic handicap in low-birthweight infants [ 10,181. Further MRI investigation is needed to clarify the link between the changes in the white matter and their clinical significance in children. It was of interest with respect to the aging process of the brain that cranial MRI findings in progerioid CS patients resembled those reported in the elderly [5-71. In the elderly, Hunt et al. reported that there was no correlation between the neuropsychologic function and the presence of PVH or WMH on MRI and concluded that only white matter changes were of doubtful clinical significance [6]. Recently, Leys et al. also reported a lack of correlation of MRI white matter and periventricular hyperintensity with age or mental status in the elderly [7]. Our results were Table 1. MRI findings patients and controls
and neuropsychologic
MRI Patient No./ Age (yrs)
Grade PVH
Grade WMH
test results
in CS
Neuropsychologic Impairment Motor Mental
CS Patients
l/l3
3
3
Moderate
Mild
218
3
3
Severe
Severe
3/10
3
3
Severe
Severe
0
0
None
None
Controls 5-12/6-I5 Abbreviations: PVH = Periventricular WMH = White matter
hyperintensity hyperintensity
consistent with those of the elderly, concluded by these authors, although it is still in question whether the MRI findings in the elderly can be applied to those of children. Neuropathologic studies of CS have demonstrated that the most constant findings are white matter and cerebeIlar atrophy with patchy demyelination and calcification in the basal ganglia with a variable degree of cerebral and cerebellar calcification [ 19-211. In demyelinating diseases the increase in water and the resultant PVH or WMH were said to result from the destruction of hydrophobic myelin. PVH or WMH, however, was also observed in normal elderly patients. Zimmerman et al. proposed the physiologic rather than the pathophysiologic explanation that PVH may be a reflection of the higher proportion of interstitial water at the ventricular lining resulting from concentric bulk flow within the white matter from the larger more peripheral site toward the more confined periventricular region in the normal elderly [ 171. Furthermore, marked variability in the intensity and extent of individual brain lesions has been observed in CS. This variability led different authors to stress different aspects of the neuropathologic picture. Crome and Kanjilal referred to the changes in their patients as “calcifying vasopathy of the brain” and considered the white matter changes to be angiopathy [21]. The diffuse white matter lesions observed on MRI in CS patients may potentially represent diffuse subcortical arteriosclerotic encephalopathy, which is usually observed in the elderly. These physiologic and pathologic similarities to aging brain may be one explanation for the lack of a link between neurologic impairment and MRI white matter changes in CS.
References [l] Coclcayne EA. Dwarfism with retinal atrophy and deafness. Arch Dis Child 1936;11:1-8. [2] Sugarman GI, Landing BH, Reed WB. Cockayne syndrome: Clinical study of two patients and neuropathologic findings in one. Clin Pediatr 1977;16:225-32. [3] Dabbagh 0. Swaiman KF. Cockayne syndrome: MRI correlates of hypomyelination. Pediatr Neurol 1988;4: 113-6. [4] Boltshauser E. Yalcinkaya C, Wichmann W, Reutter F, Prader A, Valavanis A. MIU in Cockayne syndrome type I. Neuroradiology 1989;3 I:2767.
Sugita et al: MRI in Cockayne
Syndrome
297
[5] Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJNR 1987;8:421-6. [6] Hunt AL, Orrison WW, Yeo RA, et al. Clinical significance of MRI white matter lesions in the elderly. Neurology 1989;39:1470-4. [7] Leys D, Soetaert G, Petit H, Fauquette A. Pruvo J-P, Steinling M. Periventricular and white matter magnetic resonance imaging hyperintensities do not differ between Alzheimer’s disease and normal aging, Arch Neurol 1990:47:524-7. [8] Suglta K, Takanashi J, Suzuki N. Niimi H. Comparison of cellular sensitivity to uv killing with neuropsychological impairment in Cockayne syndrome patients. Brain Dev 1991;13:163-6. [9] Suglta K, Iai M. Tamai K, Aihara M, Arima M. UV or x-ray sensitivity of cells from Cockayne syndrome. No To Hattatsu 1986;lS: 286-91. [lo] Suglta K, Takeuchi A, Iai M, Tanabe Y. Neurologic sequelae and MRI in low-birth weight patients. Pediatr Neurol 1989;5:365-9. [ll] Shimazu M. ed. Revised K-form developmental test. Nakanishi Press, Kyoto, 1985; 103-24. [12] Sugita K, Iai M, Inoue T, Ohta R. Normative data and the effect of correction for prematurity on test scores in the psychomotor development of extremely low birthweight infants. Brain Dev 1990;12: 334-8.
298
PEDIATRIC
NEUROLOGY
Vol. 8 No. 4
[13] Lowry RB. Early onset of Cockayne syndrome. Am J Med Genet 1982;13:209-IO. [I41 Kennedy RM, Rowe VD, Kepes JJ. Cockayne syndrome: An atypical case. Neurology 1980:30: 1268-72. [15] Lanning M, Simila S. Cockayne’s syndrome, report of a case with normal intelligence. Z Kinderheilkd 1970; 109:70-5. [16] Nowell MA, Grossman RI, Hackney DB, Zimmerman RA. Goldberg HI, Bilaniuk LT. MR imaging of white matter disease in children. AJNR 1988;9:503-9. [17] Zimmerman RD. Fleming CA, Lee BCP, Saiot-Louis LA, Deck MDF. Perivennicular hyperintensity as seen by magnetic resonance: Prevalence and significance. AJNR 19867: 13-20. [18] Lipper EG, Ross GS, Heier L. Nass R. Magnetic resonance imaging in children of very low birth weight with suspected brain abnormalities. J Pediatr 1988;113:1046-9. [19] Soffer D, Grotsky W, Rapin I, Suzuki K. Cockayne syndrome: Unusual neuropathological findings and review of the literature. Ann Neurol 1979;6:340-8. [20] Moosa A, Dubowitz V. Peripheral neuropathy in Cockayne’s syndrome. Arch Dis Child 1970;45:674-7. [21] Crome L, Kanjilal GC. Cockayne’s syndrome: Case report. J Neurol Neurosurg Psychiatry 1971;34: 171-S.
