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Paediatric neuro-imaging: Diagnosis
S K Misser
, MB ChB, FCRad (D) SA
Lake Smit and Partners, Durban, South Africa
We
congratulate Professor Savvas Andronikou of the Department of
Radiology, University of Pretoria, for his spot-on diagnosis,
for which he receives the award of R1 000 from the RSSA. Dr
Misser
elaborates below on the images
and findings. Please refer to page 45 of the March 2013 issue
of the SAJR (http://dx.doi.org/10.7196/SAJR.843)
for the investigative images.
Diagnosis
Imaging and findings
A 2-year-old boy presented with microcephaly and developmental delay. The MRI images referred to above, were obtained.
The sagittal T1 (Fig. 1) sequence shows an
abnormal appearance of the corpus callosum. The entire body of
the corpus callosum is remarkably thin. Only the splenium and
part of the genu is relatively spared. Along with the posterior
frontal and parietal lobe cerebral fusion, note the absence of
the septum pellucidum and fused frontal horns of the lateral
ventricles (Figs 2 - 4). The sylvian fissures appear continuous
across the hemispheres. MRA of the intracranial vessels (Fig. 5)
demonstrates an azygous anterior cerebral artery. The
combination of features is compatible with a syntelencephaly
subtype of holoprosencephaly.
Discussion
Holoprosencephaly
(HPE) is perhaps one of the more complex and captivating
congenital brain malformations, with its striking imaging
phenotype abnormalities and complex neurological impairment.
It is characterised by failure of cleavage of the
prosencephalon, a process that usually occurs between the 18th
and 28th days of gestation. The overall incidence is much
higher than expected, with up to 1 in 250 conceptions
affected. With the immense improvement in neuro-imaging,
particularly in magnetic resonance imaging, we are now able to
delineate the specific areas of involvement including cerebral
frontal and parietal lobes, basal ganglia, thalami, orbits and
facial structures. There are four subtypes of this
malformation. The spectrum includes the classic HPE subtypes
in the De Myer classification (viz. alobar, semilobar and
lobar HPE), in addition to the fourth subtype known as the
middle interhemispheric variant of holoprosencephaly (MIH) or
syntelencephaly (Table 1). Solitary median maxillary
central incisor is one of several microforms of autosomal
dominant HPE not usually included in the classification.
MIH is a relatively milder clinical form of holoprosencephaly, first described in 1993 by Barkovich et al.1 Although akin to other forms of holoprosencephaly, MIH is thought to develop on a somewhat different pattern of midline non-cleavage. The classic subtypes of HPE all involve induction of the embryonic floor plate, and SHH is the primary gene abnormality described among several others. In contrast, in the pathogenesis of MIH it is the embryonic roof plate that is involved. Mutations of the ZIC2 gene on chromosome 13, which plays a critical role in differentiation of the roof plate of the developing embryo, have been implicated in MIH.2
The affected children present with a variety of deficits including spasticity, dystonia and oromotor dysfunction affecting feeding and speech. Seizures as well as mild cognitive and visual impairment are noted in these children. Endocrinopathy is not a common feature owing to sparing of the hypothalamus and basal forebrain. When compared with other forms of HPE, the overall functional levels including mobility, hand/arm function and speech are better in patients with MIH.
On MR imaging, MIH is characterised by abnormal fusion of the posterior frontal and parietal regions of the cerebral hemispheres. The anterior portions of the frontal lobes, olfactory tracts and the occipital lobes are usually normal. There is frequent incomplete cleavage of the heads of the caudate nuclei and thalami, but the hypothalamus and lentiform nuclei are well-separated. Almost all patients with MIH have a single or azygous anterior cerebral artery. There is a coronal configuration of the sylvian fissures which are continuous across the cerebral vertex. Frequent association with heterotopias and malformations of cortical development have been reported.3
In the presence of typical MRI features, a
reasonably confident diagnosis of syntelencephaly may be made
even antenatally.4
This radiological diagnosis may serve as a valuable tool in
prognostication and in the counselling of parents.
1. Barkovich AJ, Quint DJ. Middle interhemispheric fusion: An unusual variant of holoprosencephaly. AJNR 1993;14:431-440.
2. Brown L, Odent S, David V, et al. Holoprosencephaly due to mutations in ZIC2: Alanine tract expansion mutations may be caused by parental somatic recombination. Hum Mol Genet 2001;10:791-796.
3. Fujimoto S, Togari H, Banno T, Wada Y. Syntelencephaly associated with connected transhemispheric cleft of focal cortical dysplasia. Pediatr Neurol 1999;20:397-389.
4. Pulitzer SB, Simon EM, Crombleholme TM, Golden JA. Prenatal MR findings of the Middle Interhemispheric Variant of Holoprosencephaly. AJNR 2004;25:1034-1036.
5. Kanekar S, Shively A, Kaneda H. Malformations of ventral induction. Semin Ultrasound CT MRI 2011 32(3):200-210.
S Afr J Rad 2013;17(2):72-73. DOI:10.7196/SAJR.889