Developmental language disorder associated with polymicrogyria

Patients and methods.

We prospectively studied every child presenting with language delay seen at our Child Neurology Outpatient Clinic between January 1998 and January 2000. Our examination included the following: psychological assessment, language evaluation, neurologic examination, and neuroimaging investigation. Inclusion criteria were as follows: children should be at least 4 years of age; primary complaint of language delay; normal hearing by audiometry; IQ >70; and an informed consent form signed by parents or guardians giving permission for their children to take part in this research. Exclusion criteria were severe motor or cognitive handicap. The protocol and the informed consent were approved by the ethical committee of our university hospital.

Results.

From January 1998 to January 2001, 29 consecutive children with primary complaint of language delay were evaluated. Fourteen were excluded because of a global developmental delay, psychological evaluation revealed IQ <70, or because they did not complete all steps of the protocol. The remaining 15 children met all inclusion criteria and are the subjects of this study.

Ages ranged from 4 to 14 years (mean = 6.8) and 11 were boys. Demographic data, psychological evaluation (IQ and handedness), history of pseudobulbar difficulties, family history of developmental language delay, motor development, results of neurologic examination including the careful search for pseudobulbar signs, and neuroimaging findings are presented in table 1. Regarding imaging abnormalities, the term diffuse polymicrogyria (PMG) was used when the cortical abnormality occurred around the entire extent of the sylvian fissure, including the parietal region (figure 1), whereas the term posterior parietal PMG was used when PMG was restricted to the posterior aspects of the parietal regions, without MRI abnormality at the anterior two-thirds of the sylvian fissure. Only two children (Patients 6 and 9) showed asymmetry of polymicrogyric cortex, which predominated on the left. All other children with PMG presented symmetrical bilateral PMG (figure 2). Additional figures with representative samples of imaging abnormalities can be found in the supplementary information on the Neurology Web site (go to www.neurology.org and scroll down the Table of Contents to find the title link for this article).

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Figure 1. (Patient 11). Axial, coronal and sagittal T1-weighted images showing polymicrogyria around the sylvian fissure.

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Figure 2. (Patient 12). Curvilinear reformatting from 12 mm of depth from the cortical surface and coronal T1/IR image (thickness = 3 mm) showing diffuse polymicrogyria around the perisylvian fissure. Note that thin slices and image postprocessing techniques improve the visual display of subtle lesions on MRI.

Table 2 shows the results of the language assessment.

The analysis of the results presented in both tables prompted a further division of the findings according to the extent of the polymicrogyric cortex and the severity of the clinical manifestation: patients with posterior parietal cortical involvement tended to present with a milder form of DLD (Patients 1 through 6), while diffuse polymicrogyric perisylvian cortex involving precentral and frontal regions usually was seen in patients who presented with a severe clinical manifestation (Patients 7 through 12). The other three children had different imaging findings: one child had right frontal PMG on MRI (Patient 13), one had hypogenesis of the corpus callosum and Chiari I (Patient 14), and one had bilateral frontoparietal atrophy (Patient 15).

Discussion.

Studies have shown nonspecific MRI findings4,5⇓ in patients with developmental language disorder (DLD); however, there have been no definite structural brain abnormalities associated with DLD.1 In the current study, we described clear-cut MRI abnormalities in cortical areas involved in language processing in a group of 15 consecutive patients with DLD. All but three patients had PMG in variable degrees involving perisylvian regions or temporoparietal areas. The MRI diagnosis was based on detailed visual analysis of thin slices (3 mm or less) of high-resolution MRI, including techniques of image postprocessing such as multiplanar reconstruction and curvilinear reformatting. These techniques have been shown to improve the visual display of subtle lesions on MRI.8 Gyral abnormalities on MRI are not an “all or none” phenomenon and require expertise and optimal images. Thick MRI slices would miss most of the abnormalities described here. The in vivo diagnosis of these cortical abnormalities casts new light on the physiopathology of DLD.

Many patients with DLD will end up having developmental dyslexia (DD), which implies difficulty in learning how to read and write despite normal intelligence, emotional stability, and adequate family and educational opportunities.2,3⇓ Dyslexia can be viewed as lying within a continuum of DLD.9 Neuropathologic studies of the brains of two patients with DD and history of speech delay or language difficulty showed PMG involving the perisylvian region and left inferior frontal and superior temporal gyri.3 This anatomical distribution coincides with our findings and corroborates that a cortical anomaly involving the perisylvian region plays an important role in the pathogenesis of DD and DLD.

Most of our patients presented with bilateral and symmetric cortical abnormalities, and only three children had asymmetrical lesions: two had bilateral perisylvian PMG with predominance in the left hemisphere, and one had unilateral PMG in the right frontal lobe. Our findings suggest that left-sided predominance of the lesions is not necessarily the rule in DLD, as has been proposed by others.3,10⇓ Indeed, most of our patients presented with symmetrical cortical abnormalities.

Our findings may represent a step further in the understanding of the anatomical distribution of the cortical abnormalities in DLD. Patients with diffuse PMG around the entire sylvian fissure extending to the inferior frontal regions had a more severe clinical manifestation of DLD: they did not speak at all or had severe dysarthria. Conversely, those children whose PMG was limited to the posterior aspects of the parietal regions, without involvement of the anterior two-thirds of the sylvian fissure and frontal lobe, had milder or no dysarthria.

Children with language delay and pseudobulbar signs tend to fail at answering simple questions, and sometimes even drool. It is extremely important that the correct diagnosis of DLD be adequately applied because many patients may be perceived as mentally retarded. The wrong label and the stigma may impair their quality of life and may prevent them from attending regular schools.

The male predominance in our patients is a common finding1,11⇓ in DLD series. In one study that described 12 kindreds with familial perisylvian PMG, the authors concluded that this entity appears to be genetically heterogeneous.12 However, most of the families provided evidence suggestive of or compatible with X-linked transmission, and this may be the explanation of the male predominance. Family history was a common finding in this study and this supports the belief that DLD may be genetically determined.13-16⇓⇓⇓

The finding that eight of our patients presented mild motor delay and one had mild hemiparesis does not rule out DLD, as this term is applied when specific conditions involving mainly the language domain are considered. It is noteworthy that parents of our patients looked for medical assistance because of language delay and not for any other reason.

The complete clinical picture of perisylvian syndrome comprehends pseudobulbar palsy, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies.17,18⇓ DLD has long been considered a manifestation of pseudobulbar paresis since the first descriptions of congenital suprabulbar paresis by Worster–Drought,19-21⇓⇓ who presented a classification of speech disorders in children. Cognitive deficit is part of the syndrome, but in this study we included only individuals with normal or borderline cognitive function; otherwise, they could not be classified as having a specific developmental delay.

Epilepsy is considered to be a frequent symptom in patients with perisylvian PMG.22,23⇓ Seizures occurred in 87% of 31 patients with congenital bilateral perisylvian syndrome (CBPS),22 which probably reflected a selective referral bias of patients seen at epilepsy surgery centers. In another series,12 epilepsy occurred in 43% of patients; this series reflects a broader inclusion criteria. In the current study, although epilepsy was not an exclusion criterion, none of the patients had epilepsy. It is not unlikely, however, that a number of our patients may develop epilepsy in the future. The absence of seizures may be related to the fact that more than half of our children were 6 years old or younger. Patients with malformations of cortical development may not develop epilepsy until the second half of the first decade or even the second decade of life.22

We believe that when CBPS was first described, only patients presenting its severe form could be identified, and they indeed frequently presented epilepsy and cognitive disturbances. However, more recently, the advances in neuroimaging, especially high-resolution MRI and its postprocessing techniques, have enabled the diagnosis of more subtle forms of cortical abnormalities around the sylvian fissure. This reflects a much broader clinical picture of perisylvian syndrome than previously thought.