Acta Paediatr 81: 613-17. 1992
Neuroradiological findings in children with congenital myotonic dystrophy Y Tanabe, M Iai, K Tamai', N Fujimoto' and K Sugita' Ditrision of Neurology, Chiba Children's Hospital and Department of Pediatrics'. Chiba University School of Medicine, Chiba, Japan'
Tanabe Y, Iai M, Tamai K , Fujimoto N, Sugita K. Neuroradiological findings in children with congenital myotonic dystrophy. Acta Prediatr 1992;81:613-17. Stockholm. ISSN 0803-5253 We studied seven children with congenital myotonic dystrophy, aged 2.1-8.3 years, and the results of computed tomography and magnetic resonance imaging of the brain were analyzed and neurological development was assessed from the neqnatal period. We found that ventricular dilatation that had been seen on the first day of life in two of three infants had not progressed in sequential follow-up computed tomography scans taken at intervals of one to six years. Also, in T2-weighted magnetic resonance imagings, areas of periventricular hyperintensity were identified in all children, as well as areas of subcortical hyperintensity in one child. Further, an asphyxia1 episode had occurred at birth in five patients and the extent of the periventricular hyperintensity was found to correlate significantly with Apgar scores, indicating that the degree of perinatal asphyxia that had occurred was responsible for the abnormalities uncovered by the magnetic resonance imagings. However, there was no correlation between the neurodevelopmental outcome and the extent of the periventricularhyperintensity or ventriculomegaly. Therefore, in patients with congenital myotonic dystrophy, a neonatal episode of asphyxia can be responsible for a finding of periventricular hyperintensity, but it is unlikely that an integral part of the mental retardation is attributable to brain damage due to perinatal asphyxia. 0 Cerebral MRI, congenital myotonic dystrophy, C T Y Tanabe, Division of Neurology, Chiba Children's Hospital, 579-1 Heta-cho, Chiba, Japan 280-02
Mental retardation is a common problem in the later life of children with congenital myotonic dystrophy ( I , 2), an autosomal dominantly inherited multisystemic disease. Similarly, intellectual impairment and personality changes are also major clinical signs in adult patients with myotonic dystrophy (3-5). However, much of the etiology and pathophysiology of the brain dysfunctions in patients with both congenital and adult-onset myotonic dystrophy remain to be clarified. Recently, since the introduction of magnetic resonance imaging (MRI), several studies have noted an abnormal T2 signal intensity in the periventricular and subcortical distribution of patients with myotonic dystrophy (6-8), but the clinical significance remains unclear and only a few patients with congenital myotonic dystrophy have been examined. In this study, we have analyzed the results of computed tomography (CT) and MRI findings in patients with congenital myotonic dystrophy, so as to identify the specific abnormalities of the brain in congenital myotonic dystrophy. Also, we have investigated if the extent of ventricular dilation deteriorates with time, i.e. from the neonatal period to later life, and have compared the neuroimaging results with neurodevelopmental prognosis.
Patients and methods Patients This study comprised seven unselected patients (five males and two females). The patients were diagnosed as having congenital myotonic dystrophy based on characteristic clinical pictures at the neonatal period, including generalized hypotonia, facial diplegia, and respiratory and/or feeding difficulties, and also by identifying manifestations of myotonia in the mothers. Table 1 shows the obsteric and clinical data of these patients. Patients 3 and 4 were siblings, and four of the seven patients were preterm infants. The mean gestational age was 37.3 weeks and mean birth weight was 2.69 kg. Hydramnios was a feature of two pregnancies and three patients were delivered by caesarean section. Birth asphyxia had occurred in five patients. Apgar scores, recorded 5 min efter birth, ranged from 1 to 8. Only one patient (patient I), who was the most severely affected by asphyxiation, required mechanical ventilation. Neurodevelopmental and neuroradiological evaluation At the time of assessment of neurological development and M R I examination, the patients' ages ranged from
614
Y Tanuhe el (11.
ACTA PRDIATR 81 (1992)
Tuble 1. Obstetric and clinical data in congenital myotonic dystrophy.
Age/sex
Gestation (weeks)/Birth weight (g)
5 yr 10 mo. Male 8 yr 4 mo./Male 4 yr 1 1 mo./Female 2 yr 4 mo./Female 7 yr 5 mo./Male 2 yr 1 mo./Male 7 yr 2 mo./Male
36/ 1894 32/2200 39/2740 40/2990 40/2810 37/3270 37/2960
Patients
I 2 3 4 5 6 7
Apgar score (5 min)
Perinatal problem Hydramnios, Caesarean Caesarean Caesarean Hydramnios SDH"
I 6 6 6 5 8 8
Asphyxia
+ + +
Artificial ventilation
+
-
-
-
-
+ +
Age of unaided walking -
2yr6mo. 2 yr 3 mo. 1 yr IOmo. 2yr4mo. 1 yr 8 mo. I yr 3 mo.
DQb DTR' 12 40 54 72 40 59 69
-
-
+ + + -
"SDH = Subdural hematoma; bDQ= developmental quotient; CDTR=deep tendon reflex.
2.1 to 8.3 years. Delayed motor milestone was noted in all patients, except for one (patient 7). Patient 1 was the most severely handicapped; a quadriplegic who could not sit up by himself. Neurological development was assessed by a method described previously (9), and by the Revised K-Form Developmental Test (lo), which provides a full scale developmental quotient; the results in these patients ranged from 12 to 72, whereas the developmental quotient of normal children is greater than 95. MRI was performed using a superconducting 0.5-T system (General Electric, Milwaukee, Wisconsin), with scannings of coronal and transaxial cranial sections by T2weighted spin-echo sequences 2000/80 (TR/TE), and conventional inversion recovery sequences using a parameter of 2000/500 (TR/TI) for imaging. Cranial C T scans were performed at birth in three patients. Further C T scans of these three patients and an additional three patients were performed as follows: (a) during the first six months after birth, and (b) at intervals of one to six years, so as to assess changes in ventricular size. Two indices (1 1) were used to compare changes that occurred in ventricular size between periods (a) and (b): the frontal horn index, the greatest external diameter of the frontal bone divided by the greatest distance between the anterior horns; and the cella media index, the greatest external diameter between the temporal bones divided by the greatest distance between the lateral ventricles at the level of the cella media. Statistical analysis was performed using the Spearmans's test. Informed consent was obtained from the parents of all patients and the study protocol was approved by the research committee.
Results CTjindings
The neuroradiological findings are summarized in Table 2. Of the three children studied at the neonatal period, C T scans showed that two had moderate ventricular
dilation, but no other structural changes. In assessments using the morphometrical method mentioned above, i.e. the frontal horn index and the cella media index, in which the smaller number indicates the more prominent degree of ventricular dilation, six of seven patients were identified as having ventricular dilation on follow-up C T scans. However, no progressive ventricular dilation was found in the sequential C T scans in all five patients examined, since no significant changes in our indices were observed between periods (a) and (b). MRI.findings and clinical correlation (Table 2)
The most common MRI findings of the T2-weighted spin-echo sequences in all seven patients studied were well-defined bilateral high-intensity lesions. The extent and intensity of periventricular hyperintensity varied, from periventricular hyperintensity of small limited foci just posterior to the occipital horn (patient 7, Fig. 1) to a diffuse and continuous periventricular hyperintensity with irregular lateral margins that extended to the frontal horns of the lateral ventricle (patient 1, Fig. 2). In all patients, the increased periventricular hyperintensity signal on TZweighted spin-echo sequences corresponded in part to the low-signal area on conventional inversion recovery images. According to the increased extent and intensity, in the same manner that has been described previously (9), three grades of periventricular hyperintensity were defined: mild (patients 5, 6 and 7): limited foci of periventricular hyperintensity just posterior to the occipital horns; moderate (patients 3 and 4): "rims" of periventricular hyperintensity as found dorsolateral to the atria, extending anteriorly at most to the bodies and not to the frontal horns of the lateral ventricles; and marked (patients 1 and 2): diffuse, continuous periventricualr hyperintensity with irregular lateral margins, as was seen extending to the frontal horns of the lateral ventricles. In one patient (patient 3 ), several small high-intensity lesions were seen in the subcortical white matter of the bilateral fronto-parietal area. Ventriculomegaly was observed in six of the seven
CT at neonate Not done Not done Ventriculomegaly Ventriculomegaly Normal Not done Not done 2.21 Not done 2.90 2.3 I 3.30 2.80 5.25
FHI~ 2.67 Not done 2.86 3.43 3.42 3.71 4.38
CMI 2.53" 2.21" 2.83" 2.67a 3.08" 2.85" 4.27
FHI 2.69" 3.00" 3.14= 3.38" 3.33" 3.62" 3.87
CMIe
Later CT(b) Interval (a)-(b)
-
Marked Marked Moderate Moderate Mild Mild
Ventriculomegaly
PVHb Marked Moderate Moderate Mild Mild Mild Mild
-
-
-
-
+
-
SCHC
SCH = subcortical hyperintensity;
Marked Moderate Moderate Mild Mild Mild Mild
Loss of white matter
MRI findings
PVH = periventricular hyperintensity;
4 yr 1 1 mo. I yr 6 yr I 1 mo. I yr 9 mo. 2 yr 8 mo.
-
4 yr 10 mo.
" Defined as abnormal ventricular dilatation by the data of Meese et al. (1 1); FHI = frontal horn index; CMI =cella media index.
4 5 6 7
1 2 3
Patient
Early CT(a)
CT findings
Table 2. Neuroradiological findings in congenital Myotonic Dystrophy.
N 10
.n
-
m
---
-1 8
t
E!
$
6 16
Y Tanabe et al.
ACTA PEDIATR 81 (1992)
patients (patients 6 and 7) who had no history of birth asphyxia. Similarly, there was a significant correlation between the extent of periventricular hyperintensity and ventriculomegaly ( p < 0.05). In contrast, there was no significant correlation between the full-scale developmental quotient and periventricular hyperintensity grade or the extent of ventriculomegaly, except for the full-scale developmental quotient of the most severely handicapped child (patient 1) who had marked periventricular hyperintensity and ventriculomegaly.
Discussion Abnormal MRI findings of the brain were confirmed in all our patients with congenital myotonic dystrophy. These included distinctive periventricular hyperintensity signals on T2-weighted spin-echo sequences and a decrease in the volume of white matter, especially in the occipital lobe, that paralleled the degree of ventriculomegal y. Previous MRI studies of patients with myotonic dystrophy, mainly of the adult-onset form, have demonstrated several abnormalities of the brain, including ventriculomegaly and patchy areas of increased T2 signal in the white matter (6-8). Grantz et al. ( 6 ) found that two patients with congenital myotonic dystrophy showed periventricular hyperintensity, which was possibly due to birth asphyxia, whereas periventricular hyperintensity was not detected in juvenile-onset patients, who usually have no history of perinatal distress. However, congenital and adult-onset myotonic dystrophy cannot be compared in this regard, because the pathological background influencing the brain of congenital myotonic dystrophy during the prenatal and perinatal period, such as the dysmaturation in the developing brain and brain damage from birth asphyxia, is entirely distinct from the pathological background of adult-onset myotonic dystrophy. Our results confirmed a significant correlation between Apgar scores at birth and the extent of periventricular hyperintensity, together with a proportional atrophy of the white matter. Our MRI findings are also consistent with other studies of brain damage in Fig. 2. Patient 7. (A) Axial image on conventional inversion recovery sequences demonstrates a well-defined area of a decreased signal patients who suffered from asphyxia at preterm or at intensity immediatelyadjacent to the dorsolateral aspect of the lateral full-term delivery. Based on our limited experience, no ventricles. (B) Corresponding T2-weighted spin-echo image reveals other exogenous pathologic influences in the developing bilateral, symmetrical small foci of periventricular hyperintensity brain during the prenatal or perinatal period, except for (arrow). congenital infection (12) or perinatal asphyxia (13), can cause lesions with an increased T2 signal intensity in the white matter. Therefore, this suggests that the perivenpatients. The extent of this ventriculomegaly and the tricular hyperintensity seen in patients with congenital loss of white matter could be similarly classified in each myotonic dystrophy is caused, at least in part, by patient into three gradings as was performed for the perinatal asphyxia. grades of periventricular hyperintensity and Apgar Most neuropathological investigations (14- 18), scores ( p < 0.05). Also, an unexpected association of except for a patient found to have heterotopic foci ( 1 9), mild periventricular hyperintensity was seen in two have indicated that perinatal brain damage is induced by
ACTA PEDIATR 81 (1992)
birth asphyxia. No reports have shown findings of dysplasticity or any anomalies in the brains of patients with congenital myotonic dystrophy. However, we cannot exclude the possibility that the patients who were pathologically studied by MRI were more severely affected as neonates than the patients who had survived the neonatal period. Although we found an unexpected periventricular hyperintensity and a mild atrophy of the white matter in two non-asphyxiated patients, the possibility of an anoxic event cannot be fully negated. We ascertained, by C T scans, a ventricular enlargement in two of three patients soon after birth and verified a close correlation between ventriculomegaly and periventricular hyperintensity. Therefore, this has led us to consider that antenatal or perinatal brain damage is a common etiological factor contributing to both ventriculomegaly and periventricular hyperintensity. Destructive brain damage during fetal life can produce a finding of periventricular hyperintensity and the consequent ventricular dilation, which has been shown on later MRI investigation in our two patients who had ventriculomegaly at birth. Therfore, it is not necessarily true that the ventriculomegaly seen in the neonate with congenital myotonic dystrophy indicates that the developmental brain abnormalities resulted primarily from genetic influences, which several investigators have suggested ( 5 , 20). With regard to patients with congenital myotonic dystrophy, there have been few reports that have investigated changes in ventricular size that occur with aging by means of follow-up C T scans over a long period. Using quantitative indices, we have proved, however, that no proportional difference occurs in the ventricular size between later infancy and childhood. Thus, it can be assumed that pathological change in the brain of congenital myotonic dystrophy is not progressive and degenerative. In a British study of congenital myotonic dystrophy, Harper (1) has shown an equal intelligent quotient level in both asphyxiated and nonasphyxiated patients, whereas in another study (2) a higher incidence of mental retardation has been shown in children who had a history of perinatal distress such as perinatal anoxia. However, we could not find any significant correlation between the severity of mental impairment and the degree of structural change assessed by periventricular hyperintensity on MRI, except for two patients with severe mental retardation who had marked ventriculomegaly and the finding of periventricular hyperintensity that was diffusely extended. Therefore, it is difficult to conclude that mental retardation is attributable only to an insult to the brain such as by perinatal anoxia. The perinatal factors undoubtedly aggravate the brain organic lesion in some
CT and MRI in congenital myotonic dysrrophv
61 7
patients with congenital myotonic dystrophy and, consequently, influence neurodevelopmental outcome in later life. Thus careful obstetric and neonatal management must be maintained for both the carrying mother and the patient with congenital myotonic dystrophy.
References 1. Harper PS. Congenital myotonic dystrophy in Britain. 1. Clinical
aspects. Arch Dis Child 1975;50:505- 13 2. Dyken PR, Harper PS. Congenital dystrophica myotonica. Neurology 1973;23:465-73 3. Adie WJ. Greenfield JG. Dystrophia myotonica (myotonia atrophica). Brain 1923;46:73-127 4. Caughey JE, Myrianthopoulos NC. Dystrophia Myotonica and Related Disorders. Springfield. 111: Charles C Thomas, 1963 5. Harper PS. Genetic studies in myotonic dystrophy. DM Thesis. Oxford, UK: University of Oxford 6. Glantz RH, Wright RB, Huckman MS, Garron DC, Siege1 IM. Central nervous system magnetic resonance imaging findings in myotonic dystrophy. Arch Neurol 1988;45:36-7 7 Huber SJ, Kissel JT, Shuttleworth EC, Chakeres DW, Clapp LE, Brogan MA. Magnetic resonance imaging and clinical correlates of intellectual impairment in myotonic dystrophy. Arch Neurol 1989;46:536-40. 8. Peterson MC, Dew MS, Powe LK. High-resolution magnetic resonance imaging findings in juvenile-onset myotonic dystrophy. Arch Neurol 1989;46:481-2 9. Sugita K, Takeuchi A, Iai M, Tanabe Y. Neurologic sequelae and MRI in low-birth weight patients. Pediatr Neurol 1989; 5:365-59 10. Minema S. Revised K-form Developmental Test. Kyoto: Nakanishi Press, 1985:103 24 1 I . Meese W, Kluge W, Grumme T, Hopfenmuller W. CT evaluation of the CSF spaces of healthy persons. Neuroradiology 1980;19: 131-6. 12. Barkovich AJ. Pediatric Neuroimaging. New York: Raven Press, 1990:293-325 13. Barkovich JA, Truwit CL. Brain damage from perinatal asphyxia: correlation of MR findings with gestational age. AJNR 1990;11:1087-96 14. Bossen EH, Shelburne JD, Verkauf BS. Respiratory muscle involvement in infantile myotonic dystrophy. Arch Pathol 1974;97:250-2 15. Chudley AE, Barmada MA. diaphragmatic elevation in neonatal myotonic dystrophy. Am J Dis Child 1979;133:1182-5 16. Sarnat HB, O’Connor T, Byrne PA. Clinical effects of myotonic dystrophy on pregnancy and the neonate. Arch Neurol 1976; 33:459-65 17. Silver MM, Vilos GA, Silver MD, Shaheed WS, Turner KL. Morphologic and morphometric analyses of muscle in the neonatal myotonic dystrophy syndrome. Hum Pathol 1984; 15:1171-82 18. Young RSY, Gang DL, Zalneraitis EL, Krishnamoorthy KS. Dysmaturation in infants of the mothers with myotonic dystrophy. Arch Neurol 1981;38:716-19 19. Rosman NP, Kakulas BA. Mental deficiency associated with muscular dystrophy. Brain 1966;89:769-87 20. Harper PS. Myotonic Dystrophy, 2nd Edn. Philadelphia: WB Saunders, 1989:187-225 Received June 17, 1991. Accepted Oct. 7, 1991
Neuroradiological findings in children with congenital myotonic dystrophy Y Tanabe, M Iai, K Tamai', N Fujimoto' and K Sugita' Ditrision of Neurology, Chiba Children's Hospital and Department of Pediatrics'. Chiba University School of Medicine, Chiba, Japan'
Tanabe Y, Iai M, Tamai K , Fujimoto N, Sugita K. Neuroradiological findings in children with congenital myotonic dystrophy. Acta Prediatr 1992;81:613-17. Stockholm. ISSN 0803-5253 We studied seven children with congenital myotonic dystrophy, aged 2.1-8.3 years, and the results of computed tomography and magnetic resonance imaging of the brain were analyzed and neurological development was assessed from the neqnatal period. We found that ventricular dilatation that had been seen on the first day of life in two of three infants had not progressed in sequential follow-up computed tomography scans taken at intervals of one to six years. Also, in T2-weighted magnetic resonance imagings, areas of periventricular hyperintensity were identified in all children, as well as areas of subcortical hyperintensity in one child. Further, an asphyxia1 episode had occurred at birth in five patients and the extent of the periventricular hyperintensity was found to correlate significantly with Apgar scores, indicating that the degree of perinatal asphyxia that had occurred was responsible for the abnormalities uncovered by the magnetic resonance imagings. However, there was no correlation between the neurodevelopmental outcome and the extent of the periventricularhyperintensity or ventriculomegaly. Therefore, in patients with congenital myotonic dystrophy, a neonatal episode of asphyxia can be responsible for a finding of periventricular hyperintensity, but it is unlikely that an integral part of the mental retardation is attributable to brain damage due to perinatal asphyxia. 0 Cerebral MRI, congenital myotonic dystrophy, C T Y Tanabe, Division of Neurology, Chiba Children's Hospital, 579-1 Heta-cho, Chiba, Japan 280-02
Mental retardation is a common problem in the later life of children with congenital myotonic dystrophy ( I , 2), an autosomal dominantly inherited multisystemic disease. Similarly, intellectual impairment and personality changes are also major clinical signs in adult patients with myotonic dystrophy (3-5). However, much of the etiology and pathophysiology of the brain dysfunctions in patients with both congenital and adult-onset myotonic dystrophy remain to be clarified. Recently, since the introduction of magnetic resonance imaging (MRI), several studies have noted an abnormal T2 signal intensity in the periventricular and subcortical distribution of patients with myotonic dystrophy (6-8), but the clinical significance remains unclear and only a few patients with congenital myotonic dystrophy have been examined. In this study, we have analyzed the results of computed tomography (CT) and MRI findings in patients with congenital myotonic dystrophy, so as to identify the specific abnormalities of the brain in congenital myotonic dystrophy. Also, we have investigated if the extent of ventricular dilation deteriorates with time, i.e. from the neonatal period to later life, and have compared the neuroimaging results with neurodevelopmental prognosis.
Patients and methods Patients This study comprised seven unselected patients (five males and two females). The patients were diagnosed as having congenital myotonic dystrophy based on characteristic clinical pictures at the neonatal period, including generalized hypotonia, facial diplegia, and respiratory and/or feeding difficulties, and also by identifying manifestations of myotonia in the mothers. Table 1 shows the obsteric and clinical data of these patients. Patients 3 and 4 were siblings, and four of the seven patients were preterm infants. The mean gestational age was 37.3 weeks and mean birth weight was 2.69 kg. Hydramnios was a feature of two pregnancies and three patients were delivered by caesarean section. Birth asphyxia had occurred in five patients. Apgar scores, recorded 5 min efter birth, ranged from 1 to 8. Only one patient (patient I), who was the most severely affected by asphyxiation, required mechanical ventilation. Neurodevelopmental and neuroradiological evaluation At the time of assessment of neurological development and M R I examination, the patients' ages ranged from
614
Y Tanuhe el (11.
ACTA PRDIATR 81 (1992)
Tuble 1. Obstetric and clinical data in congenital myotonic dystrophy.
Age/sex
Gestation (weeks)/Birth weight (g)
5 yr 10 mo. Male 8 yr 4 mo./Male 4 yr 1 1 mo./Female 2 yr 4 mo./Female 7 yr 5 mo./Male 2 yr 1 mo./Male 7 yr 2 mo./Male
36/ 1894 32/2200 39/2740 40/2990 40/2810 37/3270 37/2960
Patients
I 2 3 4 5 6 7
Apgar score (5 min)
Perinatal problem Hydramnios, Caesarean Caesarean Caesarean Hydramnios SDH"
I 6 6 6 5 8 8
Asphyxia
+ + +
Artificial ventilation
+
-
-
-
-
+ +
Age of unaided walking -
2yr6mo. 2 yr 3 mo. 1 yr IOmo. 2yr4mo. 1 yr 8 mo. I yr 3 mo.
DQb DTR' 12 40 54 72 40 59 69
-
-
+ + + -
"SDH = Subdural hematoma; bDQ= developmental quotient; CDTR=deep tendon reflex.
2.1 to 8.3 years. Delayed motor milestone was noted in all patients, except for one (patient 7). Patient 1 was the most severely handicapped; a quadriplegic who could not sit up by himself. Neurological development was assessed by a method described previously (9), and by the Revised K-Form Developmental Test (lo), which provides a full scale developmental quotient; the results in these patients ranged from 12 to 72, whereas the developmental quotient of normal children is greater than 95. MRI was performed using a superconducting 0.5-T system (General Electric, Milwaukee, Wisconsin), with scannings of coronal and transaxial cranial sections by T2weighted spin-echo sequences 2000/80 (TR/TE), and conventional inversion recovery sequences using a parameter of 2000/500 (TR/TI) for imaging. Cranial C T scans were performed at birth in three patients. Further C T scans of these three patients and an additional three patients were performed as follows: (a) during the first six months after birth, and (b) at intervals of one to six years, so as to assess changes in ventricular size. Two indices (1 1) were used to compare changes that occurred in ventricular size between periods (a) and (b): the frontal horn index, the greatest external diameter of the frontal bone divided by the greatest distance between the anterior horns; and the cella media index, the greatest external diameter between the temporal bones divided by the greatest distance between the lateral ventricles at the level of the cella media. Statistical analysis was performed using the Spearmans's test. Informed consent was obtained from the parents of all patients and the study protocol was approved by the research committee.
Results CTjindings
The neuroradiological findings are summarized in Table 2. Of the three children studied at the neonatal period, C T scans showed that two had moderate ventricular
dilation, but no other structural changes. In assessments using the morphometrical method mentioned above, i.e. the frontal horn index and the cella media index, in which the smaller number indicates the more prominent degree of ventricular dilation, six of seven patients were identified as having ventricular dilation on follow-up C T scans. However, no progressive ventricular dilation was found in the sequential C T scans in all five patients examined, since no significant changes in our indices were observed between periods (a) and (b). MRI.findings and clinical correlation (Table 2)
The most common MRI findings of the T2-weighted spin-echo sequences in all seven patients studied were well-defined bilateral high-intensity lesions. The extent and intensity of periventricular hyperintensity varied, from periventricular hyperintensity of small limited foci just posterior to the occipital horn (patient 7, Fig. 1) to a diffuse and continuous periventricular hyperintensity with irregular lateral margins that extended to the frontal horns of the lateral ventricle (patient 1, Fig. 2). In all patients, the increased periventricular hyperintensity signal on TZweighted spin-echo sequences corresponded in part to the low-signal area on conventional inversion recovery images. According to the increased extent and intensity, in the same manner that has been described previously (9), three grades of periventricular hyperintensity were defined: mild (patients 5, 6 and 7): limited foci of periventricular hyperintensity just posterior to the occipital horns; moderate (patients 3 and 4): "rims" of periventricular hyperintensity as found dorsolateral to the atria, extending anteriorly at most to the bodies and not to the frontal horns of the lateral ventricles; and marked (patients 1 and 2): diffuse, continuous periventricualr hyperintensity with irregular lateral margins, as was seen extending to the frontal horns of the lateral ventricles. In one patient (patient 3 ), several small high-intensity lesions were seen in the subcortical white matter of the bilateral fronto-parietal area. Ventriculomegaly was observed in six of the seven
CT at neonate Not done Not done Ventriculomegaly Ventriculomegaly Normal Not done Not done 2.21 Not done 2.90 2.3 I 3.30 2.80 5.25
FHI~ 2.67 Not done 2.86 3.43 3.42 3.71 4.38
CMI 2.53" 2.21" 2.83" 2.67a 3.08" 2.85" 4.27
FHI 2.69" 3.00" 3.14= 3.38" 3.33" 3.62" 3.87
CMIe
Later CT(b) Interval (a)-(b)
-
Marked Marked Moderate Moderate Mild Mild
Ventriculomegaly
PVHb Marked Moderate Moderate Mild Mild Mild Mild
-
-
-
-
+
-
SCHC
SCH = subcortical hyperintensity;
Marked Moderate Moderate Mild Mild Mild Mild
Loss of white matter
MRI findings
PVH = periventricular hyperintensity;
4 yr 1 1 mo. I yr 6 yr I 1 mo. I yr 9 mo. 2 yr 8 mo.
-
4 yr 10 mo.
" Defined as abnormal ventricular dilatation by the data of Meese et al. (1 1); FHI = frontal horn index; CMI =cella media index.
4 5 6 7
1 2 3
Patient
Early CT(a)
CT findings
Table 2. Neuroradiological findings in congenital Myotonic Dystrophy.
N 10
.n
-
m
---
-1 8
t
E!
$
6 16
Y Tanabe et al.
ACTA PEDIATR 81 (1992)
patients (patients 6 and 7) who had no history of birth asphyxia. Similarly, there was a significant correlation between the extent of periventricular hyperintensity and ventriculomegaly ( p < 0.05). In contrast, there was no significant correlation between the full-scale developmental quotient and periventricular hyperintensity grade or the extent of ventriculomegaly, except for the full-scale developmental quotient of the most severely handicapped child (patient 1) who had marked periventricular hyperintensity and ventriculomegaly.
Discussion Abnormal MRI findings of the brain were confirmed in all our patients with congenital myotonic dystrophy. These included distinctive periventricular hyperintensity signals on T2-weighted spin-echo sequences and a decrease in the volume of white matter, especially in the occipital lobe, that paralleled the degree of ventriculomegal y. Previous MRI studies of patients with myotonic dystrophy, mainly of the adult-onset form, have demonstrated several abnormalities of the brain, including ventriculomegaly and patchy areas of increased T2 signal in the white matter (6-8). Grantz et al. ( 6 ) found that two patients with congenital myotonic dystrophy showed periventricular hyperintensity, which was possibly due to birth asphyxia, whereas periventricular hyperintensity was not detected in juvenile-onset patients, who usually have no history of perinatal distress. However, congenital and adult-onset myotonic dystrophy cannot be compared in this regard, because the pathological background influencing the brain of congenital myotonic dystrophy during the prenatal and perinatal period, such as the dysmaturation in the developing brain and brain damage from birth asphyxia, is entirely distinct from the pathological background of adult-onset myotonic dystrophy. Our results confirmed a significant correlation between Apgar scores at birth and the extent of periventricular hyperintensity, together with a proportional atrophy of the white matter. Our MRI findings are also consistent with other studies of brain damage in Fig. 2. Patient 7. (A) Axial image on conventional inversion recovery sequences demonstrates a well-defined area of a decreased signal patients who suffered from asphyxia at preterm or at intensity immediatelyadjacent to the dorsolateral aspect of the lateral full-term delivery. Based on our limited experience, no ventricles. (B) Corresponding T2-weighted spin-echo image reveals other exogenous pathologic influences in the developing bilateral, symmetrical small foci of periventricular hyperintensity brain during the prenatal or perinatal period, except for (arrow). congenital infection (12) or perinatal asphyxia (13), can cause lesions with an increased T2 signal intensity in the white matter. Therefore, this suggests that the perivenpatients. The extent of this ventriculomegaly and the tricular hyperintensity seen in patients with congenital loss of white matter could be similarly classified in each myotonic dystrophy is caused, at least in part, by patient into three gradings as was performed for the perinatal asphyxia. grades of periventricular hyperintensity and Apgar Most neuropathological investigations (14- 18), scores ( p < 0.05). Also, an unexpected association of except for a patient found to have heterotopic foci ( 1 9), mild periventricular hyperintensity was seen in two have indicated that perinatal brain damage is induced by
ACTA PEDIATR 81 (1992)
birth asphyxia. No reports have shown findings of dysplasticity or any anomalies in the brains of patients with congenital myotonic dystrophy. However, we cannot exclude the possibility that the patients who were pathologically studied by MRI were more severely affected as neonates than the patients who had survived the neonatal period. Although we found an unexpected periventricular hyperintensity and a mild atrophy of the white matter in two non-asphyxiated patients, the possibility of an anoxic event cannot be fully negated. We ascertained, by C T scans, a ventricular enlargement in two of three patients soon after birth and verified a close correlation between ventriculomegaly and periventricular hyperintensity. Therefore, this has led us to consider that antenatal or perinatal brain damage is a common etiological factor contributing to both ventriculomegaly and periventricular hyperintensity. Destructive brain damage during fetal life can produce a finding of periventricular hyperintensity and the consequent ventricular dilation, which has been shown on later MRI investigation in our two patients who had ventriculomegaly at birth. Therfore, it is not necessarily true that the ventriculomegaly seen in the neonate with congenital myotonic dystrophy indicates that the developmental brain abnormalities resulted primarily from genetic influences, which several investigators have suggested ( 5 , 20). With regard to patients with congenital myotonic dystrophy, there have been few reports that have investigated changes in ventricular size that occur with aging by means of follow-up C T scans over a long period. Using quantitative indices, we have proved, however, that no proportional difference occurs in the ventricular size between later infancy and childhood. Thus, it can be assumed that pathological change in the brain of congenital myotonic dystrophy is not progressive and degenerative. In a British study of congenital myotonic dystrophy, Harper (1) has shown an equal intelligent quotient level in both asphyxiated and nonasphyxiated patients, whereas in another study (2) a higher incidence of mental retardation has been shown in children who had a history of perinatal distress such as perinatal anoxia. However, we could not find any significant correlation between the severity of mental impairment and the degree of structural change assessed by periventricular hyperintensity on MRI, except for two patients with severe mental retardation who had marked ventriculomegaly and the finding of periventricular hyperintensity that was diffusely extended. Therefore, it is difficult to conclude that mental retardation is attributable only to an insult to the brain such as by perinatal anoxia. The perinatal factors undoubtedly aggravate the brain organic lesion in some
CT and MRI in congenital myotonic dysrrophv
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patients with congenital myotonic dystrophy and, consequently, influence neurodevelopmental outcome in later life. Thus careful obstetric and neonatal management must be maintained for both the carrying mother and the patient with congenital myotonic dystrophy.
References 1. Harper PS. Congenital myotonic dystrophy in Britain. 1. Clinical
aspects. Arch Dis Child 1975;50:505- 13 2. Dyken PR, Harper PS. Congenital dystrophica myotonica. Neurology 1973;23:465-73 3. Adie WJ. Greenfield JG. Dystrophia myotonica (myotonia atrophica). Brain 1923;46:73-127 4. Caughey JE, Myrianthopoulos NC. Dystrophia Myotonica and Related Disorders. Springfield. 111: Charles C Thomas, 1963 5. Harper PS. Genetic studies in myotonic dystrophy. DM Thesis. Oxford, UK: University of Oxford 6. Glantz RH, Wright RB, Huckman MS, Garron DC, Siege1 IM. Central nervous system magnetic resonance imaging findings in myotonic dystrophy. Arch Neurol 1988;45:36-7 7 Huber SJ, Kissel JT, Shuttleworth EC, Chakeres DW, Clapp LE, Brogan MA. Magnetic resonance imaging and clinical correlates of intellectual impairment in myotonic dystrophy. Arch Neurol 1989;46:536-40. 8. Peterson MC, Dew MS, Powe LK. High-resolution magnetic resonance imaging findings in juvenile-onset myotonic dystrophy. Arch Neurol 1989;46:481-2 9. Sugita K, Takeuchi A, Iai M, Tanabe Y. Neurologic sequelae and MRI in low-birth weight patients. Pediatr Neurol 1989; 5:365-59 10. Minema S. Revised K-form Developmental Test. Kyoto: Nakanishi Press, 1985:103 24 1 I . Meese W, Kluge W, Grumme T, Hopfenmuller W. CT evaluation of the CSF spaces of healthy persons. Neuroradiology 1980;19: 131-6. 12. Barkovich AJ. Pediatric Neuroimaging. New York: Raven Press, 1990:293-325 13. Barkovich JA, Truwit CL. Brain damage from perinatal asphyxia: correlation of MR findings with gestational age. AJNR 1990;11:1087-96 14. Bossen EH, Shelburne JD, Verkauf BS. Respiratory muscle involvement in infantile myotonic dystrophy. Arch Pathol 1974;97:250-2 15. Chudley AE, Barmada MA. diaphragmatic elevation in neonatal myotonic dystrophy. Am J Dis Child 1979;133:1182-5 16. Sarnat HB, O’Connor T, Byrne PA. Clinical effects of myotonic dystrophy on pregnancy and the neonate. Arch Neurol 1976; 33:459-65 17. Silver MM, Vilos GA, Silver MD, Shaheed WS, Turner KL. Morphologic and morphometric analyses of muscle in the neonatal myotonic dystrophy syndrome. Hum Pathol 1984; 15:1171-82 18. Young RSY, Gang DL, Zalneraitis EL, Krishnamoorthy KS. Dysmaturation in infants of the mothers with myotonic dystrophy. Arch Neurol 1981;38:716-19 19. Rosman NP, Kakulas BA. Mental deficiency associated with muscular dystrophy. Brain 1966;89:769-87 20. Harper PS. Myotonic Dystrophy, 2nd Edn. Philadelphia: WB Saunders, 1989:187-225 Received June 17, 1991. Accepted Oct. 7, 1991
