Cerebral ventricular dilation in congenital myotonic dystrophy

Cerebral ventricular dilation in congenital myotonic dystrophy

Cerebral ventricular dilation in congenital myotonic dystrophy R. R e g e v , MD, L. S. d e Vries, MD, J. Z. H e c k m a t t , MB, ChB, MRCP, a n d V...

2MB Sizes 0 Downloads 202 Views

Cerebral ventricular dilation in congenital myotonic dystrophy R. R e g e v , MD, L. S. d e Vries, MD, J. Z. H e c k m a t t , MB, ChB, MRCP, a n d V. Dubowitz, BSe, PhD, MD, FRCP, DCH From the Department of P,aediatrics and Neonatal Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London

Ultrasonography or computed tomography scanning of the brain was performed in 10 infants with congenital myotonic dystrophy between the a g e of I day and 2 months, and showed intracranial abnormalites in all. Ventricular dilation was diagnosed in eight (80%), subarachnoid hemorrhage in one, and white matter infarcts in one. The common finding of ventricular dilation is probably related to developmental brain abnormality dating back to fetal life, because it was already present in three infants scanned on the first day of life. Neonatal asphyxia was present in seven infants, associated with intraventricular hemorrhage in two. The relationship between these changes and mental retardation, which is a c o m m o n feature in this disease, is unclear. (J PI~DIATR1987;111:372-6)

Congenital myotonic dystrophy, a dominantly inherited disease in which the mother is always the affected parent, 1,2 is characterized by hypotonia, facial weakness, respiratory and feeding difficulties, 3 and variable deformities such as talipes equinovarus. There is often associated polyhydramnios, which may be a factor in the frequent occurrence of preterm labor. Infants who survive the neonatal period may have mental retardation, the underlying pathogenesis of which is not clear. Some reports have attributed it to fetal impairment in brain development4; others have emphasized the later progessive changes in the brain, relating them to the typical mental status of adult patients with myotonia? We report the frequent association of neonatal intracranial abnormalities in congenital myotonic dystrophy, as identified during routine imaging with ultrasonography. METHODS The patients included in the study were admitted to the Hammersmith Hospital Regional Neonatal Unit or referred to our Muscle Clinic during 1982-1986. A diagnosis of congenital myotonic dystrophy was unsuspected Submitted for publication Jan. 27, 1987;accepted March 31, 1987. Reprint requests: Prof. V. Dubowitz, Department of Paediatrics and Neonatal Medicine, Hammersmith Hospital, DuCane Road, London W12 OHS, England.

372

when the baby had generalized hypotonia, facial diplegia, and respiratory and feeding difficulties, and was confirmed by demonstrating clinical or electromyographic myotonia in the mother. In all babies in our unit, ultrasonography was performed through the anterior fontanelle on admission and at least weekly thereafter while inpatients, and whenever possible in the follow-up clinic. In two infants not initially assessed by us, CT scanning of the brain, rather than ultrasonography, was performed at the referring hospital, lntraventri-

[

CT IVH

Computed tomography lntraventricular hemorrhage

9

I

cular hemorrhage was graded according to the three-point grading system of Levene et al. 6 Ventricular dilation was diagnosed when the ventricular width was above the 97th centile for age] Ten babies with congenital myotonic dystrophy who had brain scans were included in this study. Three were inborn; seven were referred from other hospitals, five in the neonatal period and two at ages 2 and 7 months, respectively. RESULTS The mean gestational age of the 10 infants was 35.8 weeks (range 32 to 40 weeks), and mean birth weight 2.26

Volume 111 Number 3

Table

Ventricular dilation in congenital myotonic dystrophy

373

I. Obstetric a n d clinical data

Patient

Sex

Gestational age (wk)

1 2 3 4 5 6 7 8 9 10

F F M M M M F M M M

38 34 35 34 35 38 36 34 32 40

Hydramnios

Decreased fetal movement

Delivery

Apgar score (1/5/10 min)

+ + + + + ? + + -

+ ? ? + + ? + + + +

Cesarean Vaginal Vaginal Cesarean Vaginal Vaginal Cesarean Cesarean Vaginal Cesarean

0/3/4 1/5/8 4/5/5 5/8 2/4 1/7/4 6/7/8 4/5 7/9 1/3/5

Hypotonia

Ventilation ~

Nasogastric feeding

+ + + + + + + + + +

+ + + + + + + + -(R)

+ + + + + + + + + +

Talipes

Facial diplegia

+ + + + + + -

*Intubation and mechanical ventilation; (R), intubation for resuscitation.

T a b l e II. Brain imaging i n congenital myotonic dystrophy First ultrasound scan

Ultrasound scan on referral ( a g e )

1" 2* 3 4

Ventricular dilation Ventricular dilation Normal Normal

5 6 7 8

ND ND Normal IVH Ventricular dilation Ventricular dilation Ventricular dilation

Ventricular dilation Ventricular dilation Ventricular dilation (12 d) Bilateral IVH Ventricular dilation (23 d) ND ND Ventricular dilation (2 mo) IVH Ventricular dilation Hydrocephalus Ventricular dilation Ventricular dilation (7 mo)

Patient

9* 10

CT scan ND ND ND ND ND Subarachnoid hemorrhage Infarcts ND ND ND ND

ND, not done. *Inborn baby.

kg (range 1.33 to 4.0 kg). Obstetric and clinical data are s u m m a r i z e d in T a b l e I. H y d r a m n i o s and decreased fetal m o v e m e n t were noted in seven pregnancies. Five infants were delivered by cesarean section. N e o n a t a l asphyxia was present in seven babies, all of whom needed mechanical ventilation. On examination, all 10 infants were found to have hypotonia; nine h a d facial diplegia, a n d talipes was present in six. All infants needed subsequent nasogastric feeding. All 10 infants h a d intracranial abnormalities on imaging studies ( T a b l e II). T h e r e was ventricular dilation in eight, intraventricular h e m o r r h a g e in two, s u b a r a c h n o i d hem o r r h a g e in one, and white m a t t e r infarcts in one. O f the eight babies with ventricular dilation, three were inborn babies a n d already h a d dilation on the first day of life (Fig. 1). In two of the five referred infants, the scan had previously been considered normal, but ventricular dilation was found on the first scan done by us at ages 12 days and

2 months, respectively. In the other two referred babies, ventricular dilation was present on the scans done at their local hospitals. I n t r a v e n t r i c u l a r h e m o r r h a g e was diagnosed in two babies with c o n c o m i t a n t ventricular dilation. In one i n f a n t (patient 8), this evolved into hydrocephalus, a n d s h u n t insertion was necessary at age 3 m o n t h s (Fig. 2). In the other infant (patient 4), a scan on the first day of life was reported to be normal; I V H with dilated ventricles was diagnosed on our first scan at age 23 days; repeat scans showed increase in ventricular size without evidence of increased intracranial pressure (Fig. 3, A and B). Ventricular size r e m a i n e d static in the other six infants. C T scans only were performed in two infants; one had a subarachnoid hemorrhage, the other had infarcts in each frontal lobe. D a t a a b o u t head circumference at birth were available for eight patients. T h r e e infants had m e a s u r e m e n t s on the 50th to 90th centile, three on the 10th to 50th centile, and

374

Regev et al.

Fig. t. patient 1. Ventricular dilation Seen on first day of life.

The Journal of Pediatrics September 1987

Fig. 2. Patient 8. Markedly enlarged ventricles at age 2 months, after intraventricular hemorrhage.

Fig. 3. Patient 4. A, Bilateral intraventricular hemorrhage with ventricular dilation at age 23 days. B, Marked progression of ventricular dilation at age 9 months.

two on the 10th centile. Head'circumference in the babies in whom ventrieular dilation was present on the first day of life was between the 50th and 90th centiles. Head growth was normal along the centiles in six, but was excessive in the two infants with IVH.

DISCUSSION Myotonic dystrophy is known to affect the brain, with resultant mental changes and retardation. Adult patients are hypersomnic, inactive, and apathetic3; these symptoms can be attributed to alveolar hypoventilation in sgme cases.

Volume 111 Number 3 These features can be present even in the absence of muscular signs? In some patients, the changes are progressive. Mental retardation is a common featUre in congenital myotonic dystrophy, occurring in about 70% of surviving infants 3', some cases of congenital myotonic dystrophy remain undiagnosed until the child is being examined because of suspected mental retardation: Evidence of brain involvement comes mostly from autopsy studies in adults with myotonic dystrophy; there are no pathognomonic cerebral abnormalities: Macroscopic changes have included reduced brain weight with abnormalities in gyral architecture and ventricular dilation.4,5 Microscopic changes have consisted of distortion of the cortex and heterotopia of neurons in subcortical white m a t t e r : Cytoplasmic inclusion bodies have been described in the thalamus 5.9 and are thought to be the result of some local disturbance in protein metabolism 5, Information about the brain in congenital myotonic dystrophy is sparse. Enlargement Of the ventricular system was demonstrated by Refsum et al) ~ using pneumoencephalograms in adult patients; it was progressive over a period of years, and was attributed to brain atrophy. In Harper's 3 series, the youngest patient with ventricular dilation was 2 years of age, and a pneumoeneepha|ography was done because of marked cranial enlargement. Sarnat et al) a reported three neonatal autopsies in which no specific abnormalities were found; the infants described by Harper 3 had tentorial tears and hemorrhages. Of the four patients with congenital myotonic dystrophy described by Young et al., ~2,two had ventricular dilation on brain CT scan, but this was not confirmed at autopsy, in which no specific abnormality was found. Ventricular dilation was a n almost consistent finding in our study, being present in eight (80%) of 10 infants. In only two could we directly relate the ventricular dilation to IVH, which was diagnosed concomitantly. The pathogenesis of ventrlcular dilation in the other patients is not clear. It is possible that a maternal enviromental factor, 13responsible for the hypotonic syndrome, may als0 cause cerebral dysgenesis and some damage to the ventricutar system. This damage could be e~ther a thalamic lesion obstructing the third ventricle5,9 or IVH occurring in utero, t4 which resolves by birth and leaves ventricular dilation. This might have been the case in the three babies who already had ventricular dilation on the first day of life, without evidence of IVH. Intraventricular hemorrhage with subsequent ventricular dilation occurs in about 40% of preterm infants of less than 32 weeks gestation, ~5 and is much less frequent in term infants) 6 The IVH may be associated with severe birth asPhyxia. Seven of our 10 infants had severe asphyxia

Ventricular dilation in congenital myotonic dystrophy

375

and needed vigorous resuscitation. However, in only two infants was IVH with ventricular dilation diagnosed. It is possible that in the two infants whose initial scan was reported to be normal, a small IVH (grade 2) could have been overlooked, leading later to ventricular dilation. 17 It seems unlikely that the ventricular dilation on the first day of life could be the consequence of birth asphyxia. Acquired antenatal and perinatal anoxia ~4are aggravating factors 3a3 t h a t can result in localized or generalized ischemic-hypoxic brain lesions) 8 Such events could have caused the lesions (subarachnoid hemorrhage and brain infarct) seen on CT scan in two of Our babies) 6 In the systematic examination of other hypotonic infants in the neonatal period, we have observed a high incidence of ventricular dilation in congenital (X linked) severe myotubular myopathy, which is also associated with hydramnios, a high frequency of preterm labor, birth asphyxia, and respiratory and swallowing difficulties. On the other hand, it has not been a feature of spinal muscular atrophy, in which there is usually no asphyxia at birth, nor of Prader-Willi syndrome, in which there is marked hypotonia and swallowing difficulty but usually no respiratory problems. Our data suggest that brain involvement in congenital myotonic dystrophy may date back to fetal life, and that Ventricular dilation is a common sequela. Developmental abnormalities of the brain may render it more susceptible to additional stress perinatally and postnatally, which contributes to later mental deficiency. The ventricular dilation must be closely monitored because it can be progressive and require active treatment. REFERENCES

1, Harper PS, Dyken PR. Early onset dystrophia myotonica: evidence supporting a maternal enviromental factor. Lancet 1972;2:53-5. 2. Dubowitz V. The floppy infant, 2nd ed. Clinics in developmental medicine [No. 76] Philadelphia: Lippincott, 1980. 3. Harper PS. Myotonic dystrophy. Philadelphia: WB Saunders, 1979. 4. Rosman NP, Kak-ulas BA. Mental deficiency associated with muscular dystrophy: a neuropathological study. Brain 1966; 89:769-87. 5. Culebras A, Feldman RG, Merk FB. Cytoplasmatic inclusion bodies within neurons of the thalamus in myotonic dystrophy. J Neurol Sci 1973;19:319-29. 6. Levene MI, Fawer C-L, Lamont RF. Risk factors in the development of intraventricular haemorrhage in the preterm neonate. Ai'ch Dis Child 1982;57:410-7. 7. Levene MI. Measurements of the growth of the lateral ventricle in preterm infants with real-time ultrasound. Arch Dis Child 1981;56:900-4. 8. Calderon R. Myotonic dystrophy: a neglected cause of mental retardation. J PEDIATR 1966;68:423-31.

376

Regev et al.

The Journal of Pediatrics September 1987

9. Wisniewski MH, Berry K, Spiro AJ. Ultrastructure of tha!amic neuronal inclusions in myotonic dystrophy. J Neurol Sci 1975;24:321-9. I0. Refsum S, Lonnum A, Sjaastad O, Engest A. Dystrophia myotonica: repeated pneumoencephalography studies in ten patients. Neurology 1967;17:345-8. 11. Sarnat HB, O'Conner T, Bryne PA. Clinical effects of myotonic dystrophy on pregnancy and the neonate. Arch Neurol 1976;33:459-65. 12. Young RSK, Cang DL, Zalneraitis EL, Krishnamoorthy KS. Dysmaturation in infants of mothers with myotonie dystrophy. Arch Neurol 1981;38:716-9. 13. Dyken PR, Harper PS. Congenital dystophia myotonica. Neurology 1973;2"3:465-73.

14. Larroche. JC. Fetal encephalopathies of circulatory origin. Bioi Neonate 1986;50:;61-74. 15. Levene MI, Starte DR. Longitudinal study of post-haemorrhagic ventricular dilatation in the newborn. Arch Dis Child 1981;56:905-10. 16. Fenichel GM, Webster DL; Wong WKT. Intracranial hemorrhage in the term infant. Arch Neurol 1984;41:30-4. 17. Fishman MA, Dutton RV, Okumura S. Progressive ventriculomegaly following minor intracranial hemorrage in premature infants. Dev Med Child Neurol 1984;26:725-31. 18. Siegel M J, Shaekelfold GD, Perlman JM, Fulling KH. Hypoxic-ischemic encephalopathy in term infants: diagnosis and prognosis evaluated by ultrasound. Radiology 1984;152:395-9.

BOUND VOLUMES AVAILABLE TO SUBSCRIBERS Bound volumes of the 1987 issues of THE JOURNAL OF PEDIATRICS are available to subscribers (only) from the Publisher, at a cost o f $44.00 ($60.00 international) for Vol. 110 (January-June) and Vol. 111 (July-December), shipping charges included. Each bound volume contains subject and author indexes, and all advertising is removed. Copies are shippe d within 60 days after publication of the last issue in the volume. The binding is durable buckram, with the Journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C. V. Mosby Company, Circulation Department, 11830 Westline Industrial Dr.; St. Louis, MO 63146, USA/800-325-4177, ext, 351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular Journal subscription.