A meta‐analysis of literacy and language in children with rolandic epilepsy

Smith, Anna; Bajomo, Omotomilola; Pal, Deb K.

doi:10.1111/dmcn.12856

Cited by 60 publications

(56 citation statements)

References 46 publications

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“…At the mild end is the common childhood disorder of Rolandic epilepsy (RE), frequently associated with speech and oromotor deficits, as well as reading disability, attention, and memory problems 3 . Focal seizures commonly occur during sleep and the defining electroencephalographic (EEG) abnormality is blunt centrotemporal spikes (CTS) during sleep 4 .…”

Section: Introductionmentioning

confidence: 99%

Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency – molecular profiling and functional rescue

Addis

Virdee

Vidler

et al. 2017

Sci Rep

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Mutations in the N-methyl-D-aspartate receptor (NMDAR) gene GRIN2A cause epilepsy-aphasia syndrome (EAS), a spectrum of epileptic, cognitive and language disorders. Using bioinformatic and patient data we shortlisted 10 diverse missense mutations for characterisation. We used high-throughput calcium-flux assays and patch clamp recordings of transiently transfected HEK-293 cells for electrophysiological characterization, and Western blotting and confocal imaging to assay expression and surface trafficking. Mutations P79R, C231Y, G483R and M705V caused a significant reduction in glutamate and glycine agonist potency, whilst D731N was non-responsive. These mutants, along with E714K, also showed significantly decreased total protein levels and trafficking to the cell surface, whilst C436R was not trafficked at all. Crucially this reduced surface expression did not cause the reduced agonist response. We were able to rescue the phenotype of P79R, C231Y, G483R and M705V after treatment with a GluN2A-selective positive allosteric modulator. With our methodology we were not able to identify any functional deficits in mutations I814T, D933N and N976S located between the glutamate-binding domain and C-terminus. We show GRIN2A mutations affect the expression and function of the receptor in different ways. Careful molecular profiling of patients will be essential for future effective personalised treatment options.

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Section: Introductionmentioning

confidence: 99%

Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency – molecular profiling and functional rescue

Addis

Virdee

Vidler

et al. 2017

Sci Rep

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“…Some of these comorbidities are shared among children with epilepsies traditionally considered to have a favorable prognosis, and others are unique. For example, attention deficit hyperactivity disorder (ADHD), and problems in language and executive function are all common to the syndromes of childhood absence epilepsy, rolandic epilepsy (RE) and juvenile myoclonic epilepsy [1–3]. However, RE uniquely has a strong and specific association with both reading disability (RD): Odds Ratio 5.78 (2.86–11.69), and speech sound disorder (SSD): OR 2.47 (1.22–4.97)[4].…”

Section: Introductionmentioning

confidence: 99%

Risk factors for reading disability in families with rolandic epilepsy

Vega

Smith

Cockerill

et al. 2015

Epilepsy & Behavior

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OBJECTIVE The high prevalence and impact of neurodevelopmental comorbidities in childhood epilepsy are now well known, as are the increased risks and familial aggregation of reading disability (RD) and speech sound disorder (SSD) in rolandic epilepsy (RE). The risk factors for RD in the general population include male sex, SSD and ADHD but it is not known if these are the same in RE or whether there is a contributory role of seizure and treatment related variables. METHODS An observational study of 108 RE probands (age range 3.6–22 years) and their 159 siblings (age range 1–29 years; 83 with EEG data) singly ascertained in the US or UK through an affected RE proband. We used a nested case-control design, multiple logistic regression and generalized estimating equations to test the hypothesis of association between RD and seizure variables or antiepileptic drug treatment in RE; we also assessed an association between EEG focal sharp waves and RD in siblings. RESULTS RD was reported in 42% of probands and 22% of siblings. Among probands, RD was strongly associated with a history of SSD (OR 9.64, 95% CI: 2.45–37.21), ADHD symptoms (OR 10.31, 95% CI: 2.15–49.44), and male sex (OR 3.62, 95% CI: 1.11–11.75), but not with seizure or treatment variables. Among siblings, RD was independently associated only with SSD (OR 4.30, 95%CI: 1.42–13.0) and not with the presence of interictal EEG focal sharp waves. SIGNIFICANCE The principal risk factors for RD in RE are SSD, ADHD and male sex, the same risk factors as for RD without epilepsy. Seizure or treatment variables do not appear to be important risk factors for RD in RE probands, and there was no evidence to support interictal EEG focal sharp waves as a risk factor for RD in siblings. Future studies should focus on the precise neuropsychological characterisation of RD in RE families, and on the effectiveness of standard oral-language and reading interventions.

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“…Despite the favorable prognosis, studies began to question the "benign" nature of this syndrome when faced with complaints about learning abilities and deficits in neuropsychological tests of children affected by the issue (Beaumanoir, Ballis, Varfis, & Ansari, 1974;Hermann, Jones, Jackson, & Seidenberg, 2012), especially in the areas of language, memory, attention, motor coordination and executive functions (Capelatto et al, 2012;Hwang et al, 2013;Kim, Lee, Chung, Lim & Lee, 2014;Miziara et al, 2012;Neri et al, 2012;Northcott et al, 2005;Overvliet et al, 2013;Smith et al, 2012;Smith, Bajomo, & Pal, 2015;Tovia et al, 2011;Vannest et al, 2013;Verrotti, Filippini, Matricardi, Agostinelli & Gobbi, 2014).…”

Section: Introductionmentioning

confidence: 99%

Working memory and phonological awareness in children with rolandic epilepsy

et al. 2017

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This study investigated how the difficulties in language in children with Rolandic Epilepsy (RE) could be related to alterations in their development of phonological awareness and/or working memory. We evaluated fourty-two children aged 6 to 13 years old. From these, twenty-one children were diagnosed with RE and formed the experimental group; and twenty-one children without RE, paired with the experimental group by sex, age, education and socioeconomic status, formed the control group. The results showed significant differences in the performances of children with RE and healthy children in the tests that evaluated working memory and phonological awareness. Also, positive and high significant correlations were found between working memory and phonological awareness in the RE clinical subgroup. Generally, the results suggest that compromises in both cognitive functions might be associated to loss of language capabilities in children with RE, and also point that the development of working memory and phonological awareness are interconnected.

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A meta‐analysis of literacy and language in children with rolandic epilepsy

Cited by 60 publications

References 46 publications

Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency – molecular profiling and functional rescue

Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency – molecular profiling and functional rescue

Risk factors for reading disability in families with rolandic epilepsy

Working memory and phonological awareness in children with rolandic epilepsy

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