Our report can be considered original since we describe the earliest clinical presentation and diagnosis of a primary or congenital type of DDM. Early diagnosis in this case could be achieved thanks to a group with experience in pediatric dysmorphology.
In our patient isolated unilateral ventriculomegaly, detected on prenatal US, was confirmed to be related to hemispheric hypotrophy on neonatal transcranial US and MRI. Transcranial Doppler US arose suspicion of left MCA anomaly so we performed a contrast enhanced-MRI angiography that confirmed the reduced caliber of the left MCA and its segments concomitant to unilateral brain hypoplasia.
Clinically apart from the isolated depression exhibited at birth, our patient did not suffer respiratory distress, encephalopathy or multiorgan dysfunction. She showed transient weak suction and an isolated axial hypotonia of central origin persistent at two months with a normal spontaneous motility. Thus until the second month of age, clinical evidence of hemisyndrome in terms of posture, asymmetry of resting muscular tone or spontaneous motility was not present. The normal latency of the principal fVEP component, in the presence of a left occipital lobe hypotrophy, is compatible with the supposed subcortical generators of fVEP [
2]. Nystagmus, immaturity of eye fixation and pursuit may be ascribed to impairment of functionally related cortical and subcortical areas. The first peculiar findings of DDMS, face asymmetry and impaired left upper limb function, emerged by six months of age and at 9 months of age right sided hemiplegia and body hypotrophy affecting also the limbs were clearly evident. Body hypoplasia affecting principally the limbs, contralateral to the atrophic hemisphere and associated with superficial sensory deficit and hemiplegia, can be considered secondary to the impaired hemispheric functions.
In our patient isolated unilateral ventriculomegaly (atrial width 11,8 mm) was detected on prenatal US at 32 + 2 GW. Clinical series suggest that at between 15 and 40 GW, on prenatal ultrasound evaluation, an atrial width of < 10 mm is indicative of normal cerebral ventricular size. Ventriculomegaly corresponds to an atrial width of ≥ 10 mm and is considered mild when the atrial width is between 10 and 12 mm, moderate if 13-15 mm and severe when ≥ 16 mm [
6]. Cerebral lateral ventricular asymmetry, with the two asymmetric atrial width of < 10 mm, is considered a normal variant and is prevalent in male [
7]. Ventriculomegaly can be primarily related to blockage of cerebrospinal fluid outflow through the foramen of Monro or ipsilateral reduced brain tissue with concomitant ex-vacuo ventricular enlargement. Shen et al. described three patterns of CH on MRI: pattern I, diffuse cortical and subcortical atrophy; pattern II, diffuse cortical atrophy associated with expanded porencephalic cysts; and pattern III, old infarction with necrosis in the territory of the MCA [
8]. In our patient at two months of age brain MRI showed a pattern I of CH with peculiar bone and parenchymal changes. Concomitant encephalomalacia has been detected in two of the four reported one-year-old patients with DDMS [
4]. In our patient no hypoxic ischemic parenchymal lesion was present. Several pathological conditions are associated with fetal/neonatal CH (Table
1). Cerebral hemispheric hypoperfusion can be due to aortic coarctation, internal carotid hypoplasia or agenesia, and reduced or absent middle cerebral artery (MCA) and/or its ramifications development [
9]. On the basis of the described congenital vascular changes, hemispheric hypoperfusion, occurring during early brain development, is considered in literature the prevalent etiopathogenic hypothesis for CH in the congenital type of DDMS. DDMS and cerebral migration disorders are associated with abnormalities that affect the development of cerebral arteries and the persistence of embryonic arteries, Dandy Walker malformation and cerebellar malformations, as well as congenital vascular abnormalities, such as facial hemangioma and reticulated capillary malformations have been described [
10]. These findings suggest a common angiogenetic developmental anomaly occurring during the same embryonic period, approximately 4-5 weeks [
11]. Male sex and left hemisphere predisposition to vascular impairment has been reported in DDMS [
3]. Ipsilateral polymicrogyria, mesencephalon and brainstem hypoplasia and crossed cerebellar atrophy are occasionally present [
12‐
14]. At two months of age a contrast enhanced-MR angiography showed a normal appearing of the arteries of the neck (internal carotid arteries and vertebral arteries) and intracranially a reduced caliber of the left middle artery cerebral involving the M1, M2 and M3 segments. The posterior cerebral arteries were within normal limits. Congenital middle cerebral artery hypoplasia must be differentiated from cerebral artery occlusion predisposing to arterial stroke due to thromboembolic events, infectious and non–infectious inflammatory conditions, genetic pathologies, inborn errors of metabolism. Diagnosis of fetal, neonatal, or presumed fetal or neonatal stroke can be made on the basis on clinical history, physical examination, laboratory findings and brain imaging showing peculiar localization and evolution of parenchymal infarct [
15].
Table 1
Congenital and acquired conditions associated with fetal/neonatal cerebral hemiatrophy
Cerebral hemispheric hypoperfusion [ 11] | Periventricular leucolamalacia, |
Brain dysgenesis (schizencephaly, polymicrogyria) | Cerebral hemorrage |
Septo-optic dysplasia | Cerebral infarction |
Sturge-Weber syndrome | Cerebral infection |
Silver-Russel syndrome | |
Encephalocraniocutaneous lipomatosis [ 9] | |
Schimmelpenning syndrome [ 10] | |