Aravindhan Veerapandiyan

Social skills and associated psychopathology in children with chromosome 22q11.2 deletion syndrome: implications for interventions

BACKGROUND Although distinctive neuropsychological impairments have been delineated in children with chromosome 22q11 deletion syndrome (22q11DS), social skills and social cognition remain less well-characterised. OBJECTIVE To examine social skills and social cognition and their relationship with neuropsychological function/behaviour and psychiatric diagnoses in children with 22q11DS. METHODS Sixty-six children with 22q11DS and 54 control participants underwent neuropsychological testing and were administered the Diagnostic Analysis of Non-Verbal Accuracy (DANVA) for face and auditory emotion recognition, a measure of social cognition: their parents/guardians were administered the Social Skills Rating System (SSRS) - parent version, Child Behavior Checklist (CBCL) - parent version and the Computerised Diagnostic Interview Schedule for Children (C-DISC). RESULTS The 22q11DS group exhibited significantly lower social skills total score and more problem social behaviours, lower neurocognitive functioning, higher rates of anxiety disorders and more internalising symptoms than the control group. Participants with 22q11DS also exhibited significant deficits in their ability to read facial expressions compared with the control group, but performed no differently than the control participants in the processing of emotions by tone of voice. Within the 22q11DS group, higher social competency was correlated with higher global assessment of functioning and parental socio-economic status. Social competency was worse in those with anxiety disorders, attention deficit hyperactivity disorder, more than two psychiatric diagnoses on the C-DISC and higher internalising symptoms. No significant correlations of SSRS scores were seen with IQ, executive functions, attention, or verbal learning and memory. No correlations were found between social cognition and social skill scores. CONCLUSION Our results indicate that social skills in children with 22q11DS are associated with behaviour/emotional functioning and not with neurocognition. Thus, treating the behaviour or emotional problems such as attention deficit hyperactivity disorder and anxiety disorders may provide a pathway for improving social skills in these children.

Structural connectivity of the frontal lobe in children with drug-resistant partial epilepsy

The superior longitudinal fasciculus (SLF) II and cingulum are two white matter tracts important for attention and other frontal lobe functions. These functions are often disturbed in children with drug-resistant (DR) partial epilepsy, even when no abnormalities are seen on conventional MRI. We set out to determine whether abnormalities in these structures might be depicted on diffusion tensor imaging (DTI) studies in the absence of abnormalities on conventional MRI. We compared the DTI findings of 12 children with DR partial epilepsy with those of 12 age- and gender-matched controls. We found that the SLF II fractional anisotropy (FA) values of the patients were significantly lower than those of the controls (means: 0.398±0.057 and 0.443±0.059, respectively, P=0.002). Similarly, apparent diffusion coefficient (ADC) and parallel diffusivity values for SLF II were also significantly lower in the patients. There were no differences in the FA and ADC values of the cingulum. Our findings are consistent with abnormal structural connectivity of the frontal lobe in children with DR partial epilepsy and provide a possible explanation for the previously reported functional abnormalities related to the SLF II in these patients.

Oculogyric crises secondary to lamotrigine overdosage

We report four patients with no preexisting movement disorders who developed oculogyric crises secondary to lamotrigine toxicity and had resolution of these crises after dose reduction. Episode numbers ranged from 1–20 per day and episode duration from 2 s to several hours. Mean plasma concentration of lamotrigine at the time of oculogyric crisis was 15.5 μg/mL, with a mean dose of 16 mg/kg per day.

Seizure predisposition after perinatal hypoxia: Effects of subsequent age and of an epilepsy predisposing gene mutation

There is a gap in our knowledge of the factors that modulate the predisposition to seizures following perinatal hypoxia. Herein, we investigate in a mouse model the effects of two distinct factors: developmental stage after the occurrence of the perinatal insult, and the presence of a seizure predisposing mutation.

Electroencephalographic and seizure manifestations in two patients with folate receptor autoimmune antibody-mediated primary cerebral folate deficiency

Seizure semiology and electroencephalographic (EEG) manifestations of autoimmune-mediated cerebral folate deficiency (CFD) before and after therapy have yet to be fully characterized. Here, we report these findings in two such patients. Our first patient presented with the novel manifestation of infantile spasms at the age of 3months, while the second developed the previously reported initial onset of tonic seizures with static developmental delay, but subsequently manifested the novel finding of electrical status epilepticus in sleep at the age of 15years. Awareness of these new manifestations, together with the previously reported manifestations of developmental delay, seizure onset during the first 2years of life, occurrence of tonic, myoclonic-astatic, absence, and generalized tonic-clonic seizures, with an EEG of generalized spike-slow waves and multifocal spikes, is important to increase the index of suspicion of this treatable disorder.

Altered Development of the Dorsolateral Prefrontal Cortex in Chromosome 22q11.2 Deletion Syndrome: An In Vivo Proton Spectroscopy Study

BACKGROUND Chromosome 22q11.2 deletion syndrome (22q11DS), the most common microdeletion in humans, is associated with multiple medical features, almost universal cognitive deficits, and a high risk of schizophrenia. The metabolic basis of the psychological/psychiatric features is not well understood. Volumetric brain imaging studies have shown that gray matter abnormalities in the dorsolateral prefrontal cortex (DLPFC), an area that is believed to be integral for higher neurocognition, as well as being involved in schizophrenia, are associated with the psychological manifestations. However, studies have not characterized any possible metabolite alterations within the DLPFC of children with 22q11DS and their correlations with the psychological findings. METHODS We conducted a short echo time, single-voxel, in vivo proton spectroscopy study involving children with 22q11DS (n = 26) and matched control subjects (n = 23). RESULTS Absolute N-acetylaspartate (NAA) levels from the DLPFC were significantly elevated in children with 22q11DS compared with control subjects and the elevations were associated with poor global functioning and higher rates of comorbid attention-deficit/hyperactivity disorder. Children with 22q11DS had a lack of an age-associated decrease in NAA levels, a trend seen in the control subjects. However, the results did not remain statistically significant after corrections for multiple comparisons were made. CONCLUSIONS These findings represent the first report of proton spectroscopy in children with 22q11DS. The elevated DLPFC NAA levels and the lack of decreasing trends in NAA with age in the 22q11DS group relative to control subjects suggest an alteration in cortical development. Also, such neuronal dysmaturation is associated with psychopathology in children with 22q11DS.

Pseudometabolic presentation of dystrophinopathy due to a missense mutation

Exercise intolerance with myalgia, muscle stiffness, and recurrent rhabdomyolysis due to mutations in the DMD gene can mimic metabolic myopathies leading to delayed or inaccurate diagnoses. In this retrospective chart review, we report 3 unrelated boys with exertional myalgia, muscle stiffness, myoglobinuria, and normal neurological examination due to an identical point mutation in the DMD gene: a hemizygous T‐to‐C change in exon 15 (c.1724T>C) resulting in an amino acid substitution of leucine to proline at codon 575. Two of the 3 boys had normal dystrophin immunostaining and Western blot analysis in muscle. This missense mutation has been reported twice before, with at least 1 patient exhibiting rhabdomyolysis. Our report, however, is the first to describe in detail the clinical findings associated with this specific mutation. Further studies and clinical reports are needed to better understand the pathogenicity of the mutation. Muscle Nerve 42: 975–979, 2010

The role of cephalometry in assessing velopharyngeal dysfunction in velocardiofacial syndrome.

To report our experience with cephalometry in evaluating velopharyngeal dysfunction (VPD) in velocardiofacial syndrome (VCFS) and its utility in assessing the role of cervical spine abnormalities in VPD, prior to surgical correction of VPD.

Chromosome 22q11.2 deletion syndrome in African-American patients: a diagnostic challenge.

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with numerous and variable clinical manifestations including conotruncal heart abnormalities, palatal anomalies, hypoparathyroidism, immune deficiency, and cognitive deficits. The clinical suspicion of this syndrome is often heightened by the presence of characteristic facial features. A previous report highlighted the under‐diagnosis of this condition in African Americans, thought to be related to a paucity of typical facial features. We ascertained the largest cohort (n = 50) of African‐American individuals with 22q11DS reported thus far, across five genetics centers in the United States and report on their facial and other phenotypic features. About

Two Patients With an Anti-N-Methyl-d-Aspartate Receptor Antibody Syndrome-Like Presentation and Negative Results of Testing for Autoantibodies

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