Utility of genetic testing in the pre-surgical evaluation of children with drug-resistant epilepsy.

We evaluated the utility of genetic testing in the pre-surgical evaluation of pediatric patients with drug-resistant focal epilepsy. This single-center retrospective study reviewed the charts of all pediatric patients referred for epilepsy surgery evaluation over a 5-year period. We extracted and analyzed results of genetic testing as well as clinical, EEG, and neuroimaging data. Of 125 patients referred for epilepsy surgical evaluation, 86 (69%) had some form of genetic testing. Of these, 18 (21%) had a pathogenic or likely pathogenic variant identified. Genes affected included NPRL3 (3 patients, all related), TSC2 (3 patients), KCNH1, CHRNA4, SPTAN1, DEPDC5, SCN2A, ARX, SCN1A, DLG4, and ST5. One patient had ring chromosome 20, one a 7.17p12 duplication, and one a 15q13 deletion. In six patients, suspected epileptogenic lesions were identified on brain MRI that were thought to be unrelated to the genetic finding. A specific medical therapy choice was allowed due to genetic diagnosis in three patients who did not undergo surgery. Obtaining a molecular diagnosis may dramatically alter management in pediatric patients with drug-resistant focal epilepsy. Genetic testing should be incorporated as part of standard investigations in the pre-surgical work-up of pediatric patients with drug-resistant focal epilepsy.

"Generalized-to-focal" epilepsy: stereotactic EEG and high-frequency oscillation patterns

Objective: We aimed to clarify the pathophysiology of epilepsy involving seizures with apparently generalized onset, progressing to focal ictal rhythm through stereotactic EEG (SEEG) implantation, recording, stimulation and high-frequency oscillation (HFO) analysis. Methods: We identified two patients with seizures with bilateral electrographic onset evolving to focal ictal rhythm, who underwent SEEG implantation. Patients had pre-surgical epilepsy work-up, including prolonged video scalp EEG, brain MRI, PET, ictal/interictal SPECT, MEG, and EEG-fMRI prior to SEEG implantation. Results: Both patients had childhood-onset seizures involving behavioural arrest and left versive head and eye deviation, evolving to bilateral tonic-clonic convulsions. Seizures were electrographically preceded by diffuse, bilateral 3-Hz activity resembling absence seizures. Both had suspected focal lesions based on neuroimaging, including 3T MRI and voxel-based post-processing in one patient. Electrode stimulation did not elicit any habitual electroclinical seizures. HFO analysis showed bilateral focal regions with high fast-ripple rates. Significance: "Generalized-to-focal" seizures may occur due to a diffuse, bilateral epileptic network, however, both patients showed ictal evolution from a generalized pattern to a single dominant focus which may explain why the focal aspect of their seizures had a consistent clinical semiology. Patients such as these may have a unique form of generalized epilepsy, but focal/multifocal cerebral abnormalities are also a possibility.

Ictal biting injuries in the epilepsy monitoring unit, a cohort study of incidence and semiological significance.

PURPOSE: Oral biting injuries are widely recognized complications of seizures. Value in differentiating epileptic vs paroxysmal non-epileptic seizures is well demonstrated, but frequency and semiological value are poorly described. We aimed to evaluate frequency in an epilepsy monitoring unit setting as well as semiological value. MATERIAL AND METHODS: Systematic evaluation of ictal oral injuries was provided by the nursing staff on the Epilepsy Monitoring Unit. Cases were identified by chart review. Demographic, diagnostic and seizure-related data were collected from medical records and video-EEG recording, and correlated with location of tongue laceration. Lateralized oral lacerations while recumbent were further analyzed to eliminate contribution of body position. RESULTS: 89 events were reported in 52 individuals (5.6% of all admissions or 8.3% of patients with epileptic seizures). Lacerations occurred in 88 epileptic seizures (80 generalized, three focal, five undetermined) and one non-epileptic seizure. 87/88 had a tonic component and 86/88 had a clonic component. Lateralized tongue laceration occurred in 30 patients. This correlated with body position during the event but not with handedness or seizure characteristics. CONCLUSIONS: Oral biting is a common complication in the epilepsy monitoring unit. Its presence suggests a tonic or clonic component but is of no help in localizing seizure onset.

The Competency Model for Professional Rehabilitation Nursing.

BACKGROUND: Rehabilitation nursing is practiced in various settings along the healthcare continuum. No framework is noted in the literature that defines the necessary competencies of the rehabilitation nurse. PURPOSE: To develop a Competency Model for Professional Rehabilitation Nursing and its application to clinical and educational practice. METHOD/DESIGN: A seven-member Association of Rehabilitation Nurses (ARN) task force was convened; conducted a literature review, reviewed current and historical ARN documents, including the Strategic Plan, and developed a Competency Model for Professional Rehabilitation Nursing practice. FINDINGS: The Competency Model for Professional Rehabilitation Nursing delineates four domains of rehabilitation nursing practice and essential role competencies. CONCLUSION: The Competency Model for Professional Rehabilitation Nursing addresses this diverse specialty practice in the current healthcare arena. This framework can be used to guide nurses practicing at different levels of proficiency in various settings. CLINICAL RELEVANCE: The Competency Model can be used as a structure for staff orientation, evaluation tools, clinical ladder components, role descriptions and rehabilitation nursing courses.

Epidemiology of severe hearing impairment in a population-based cerebral palsy cohort.

BACKGROUND: Comorbidities including hearing impairment occur commonly in individuals with cerebral palsy (CP). METHODS: Hearing impairment was assessed in a registry-derived population-based sample of children with CP. RESULTS: Hearing impairment was documented in 12.7% (27 of 212) with less than a quarter of these (or 2.7% overall [6 of 212]) having a severe hearing loss of greater than 70 dB bi-aurally. Those with severe hearing impairment were more likely to be nonambulatory (Gross Motor Function Classification System IV/V; 100% versus 34.0% in the registry; P < 0.001) and have a spastic quadriplegic or dyskinetic CP variant (100% versus 42%, P = 0.001). Severe neonatal hyperbilirubinemia necessitating exchange transfusion demonstrated a striking association with hearing impairment in the context of CP in spite of small observed numbers; three of three had severe hearing loss, accounting for 50% of cases of severe hearing loss. CONCLUSIONS: These results suggest a specific CP context and antecedent conditions that necessitate a heightened vigilance for the detection and remediation of hearing impairment.

Spectrum of visual disorders in a population-based cerebral palsy cohort.

BACKGROUND: Children with cerebral palsy are known to be at increased risk for visual impairment. METHODS: In a population-based sample drawn from a geographically defined registry, the profile of visual impairment in children with cerebral palsy was investigated. RESULTS: Close to half (49.8%; 106/213) had a visual impairment. The majority of these individuals had strabismus (55.7%; 59/106) and a slightly lesser fraction had refractive errors (20.7%; 22/106) or severe visual loss (18.9%; 20/106). The vast majority of children with severe visual loss had spastic quadriplegia (83%; 17/20) or were nonambulatory (i.e., Gross Motor Function Classification Scale IV/V, 80%; 16/20). CONCLUSIONS: Knowledge of this profile will assist practitioners to heighten their appreciation of potential visual disturbances in certain subsets of children with cerebral palsy.

Homozygous deletion of Tenascin-R in a patient with intellectual disability.

BACKGROUND: TNR encodes Tenascin-R, an extracellular matrix glycoprotein that is primarily expressed in the central nervous system. Loss of TNR impairs cognition, synaptic plasticity and motor abilities in mice, however its role in human neurodevelopment and cognition is less clear. METHODS AND RESULTS: The authors present the case of a child with intellectual disability and transient choreoathetosis. Array genomic hybridisation revealed a homozygous deletion involving only two genes, including TNR. Sequencing TNR in a cohort of 219 patients with intellectual disability did not identify any potential pathogenic mutations. CONCLUSION: This is the first report of a complete loss of TNR associated with intellectual disability. This study provides evidence of the important role of TNR in brain development and cognition in humans.