Psychogenic non-epileptic seizures in children.

Psychogenic Non-Epileptic Seizures (PNES) are a relatively common condition in children. While their clinical presentation resembles epileptic seizures, the underlying cause for PNES involves a multitude of bio-psychosocial factors. Patients may be misdiagnosed with epilepsy and subjected to unnecessary treatments, often delaying the diagnosis for years. A strong understanding of its symptomatology is essential for diagnosis of PNES. Successful management depends on effective teamwork that involves the neurologist as well as mental health professionals. This paper reviews the various aspects of PNES in children with emphasis on the clinical presentation, diagnosis as well as the underlying psychological basis and treatment.

Measuring the Barriers to Adherence With Neurology Clinic Appointments for Children With Epilepsy: A Pilot Study.

INTRODUCTION: Epilepsy is one of the most common neurological disorders in children. Missed appointments reflect missed opportunity to provide care for children with epilepsy. The objective of this study was to identify social determinants of health (SDH) and other factors associated with missed appointments in children with epilepsy and measure the relation between missed appointments and frequency of emergency room (ER) visits and inpatient admissions. METHODS: This was a prospective study conducted in the neurology division at a level 4 epilepsy center. Children (0 to < 18 years of age) with a diagnosis of epilepsy were included and a semi-structured questionnaire was provided to the families. Patients with 2 or more missed neurology clinic appointments in the previous year ("study group", n = 36) were compared to those with 1 or zero missed appointments ("control group", n = 49). A comparison of the clinical characteristics, emergency room visits and hospitalizations in the past year as well as SDH was performed. Statistical analysis was performed using SPSS and p < 0.05 was considered significant. RESULTS: The mean age, gender distribution and presence of medical refractoriness were comparable between the 2 groups. Families in the study group reported a higher likelihood of having to make special work arrangements for clinic appointments. Children in the study group were noted to have a significantly higher frequency of single mother households, presence of public insurance, father not graduating from high school and household income less than 50,000 dollars. Within the preceding year, children in the study group were noted to have a higher frequency of visits to the emergency department as well as 6 times higher likelihood of inpatient hospitalization for seizures. CONCLUSIONS: Social determinants of health play an important role in determining adherence with neurology clinic visits in children with epilepsy. Children with more missed appointments are likely to have a higher frequency of visits to the emergency department as well as a higher incidence of hospitalization for seizures. Identification of high-risk families and implementation of early interventions may improve adherence to office visits and decrease emergency room visits and hospitalization for seizures.

Differential DNA Methylation Patterns in Patients with Epilepsy due to Malformations of Cortical Development: A Pilot Study.

OBJECTIVE: To study the DNA methylation profiles in brain tissue of patients with refractory epilepsy due to malformations of cortical development (MCDs). MATERIALS AND METHODS: Clinical, neuroimaging, and pathology characteristics were defined for 13 patients who underwent resective surgery for epilepsy. Methylation analysis was performed using Illumina® 450k Methylation Microarray. Data analysis was completed, and pathway identification was done using the R/Bioconductor package. RESULTS: Genes associated with Ephrin-Reelin pathway, potassium channels, and glutathione metabolism were differentially methylated in the MCD group when compared with patients who had no evidence of MCD. CONCLUSIONS: Our preliminary data reveal that epigenetic pathways may have a role in the pathobiogenesis of MCDs.

Functional Neurologic Symptom Disorder in Children: Clinical Features, Diagnostic Investigations, and Outcomes at a Tertiary Care Children's Hospital.

OBJECTIVE: To describe the presenting symptoms and short-term outcomes of children diagnosed with functional neurologic symptom disorder and to compare the demographic and clinical characteristics of children who received neurodiagnostic testing to those who did not. STUDY DESIGN: Single center, retrospective review of 222 children who presented to the emergency department of a children's hospital, and diagnosed with functional neurologic symptom disorder, between 2010 and 2015. RESULTS: Out of 222 visits (females = 156, African Americans = 130, mean age = 13.9 years), neurodiagnostic tests were performed in 102/222 (46%) visits. The most commonly performed investigations were magnetic resonance imaging (MRI) of brain (n = 37) and electroencephalogram (EEG) (n = 56) and were noted to be unremarkable in all instances. Neurodiagnostic tests were more likely to be performed in patients who (1) were non-African American (54% vs 40%; P = .03), (2) presented with new-onset symptoms (55% vs 31%; P < .01), (3) underwent hospitalization (61% vs 17%; P < .01), and (4) were evaluated by a neurologist (59% vs 9%; P < .01) or a psychiatrist (58% vs 28%; P < .01). Common clinical presentations included seizurelike or strokelike symptoms. Short-term follow-up was possible in 20%, with an alternate diagnosis of syncope, noted in only 1 child. CONCLUSIONS: Most children who presented with a functional neurologic symptom disorder in our study were noted to have seizurelike or strokelike presentations and were adolescent females. Caucasians were more likely to undergo neurodiagnostic investigations. Radiologic and neurophysiological tests were more commonly performed when neurology and psychiatry consultations were sought. Such investigations had low diagnostic utility.

Homozygous TANGO2 Single Nucleotide Variants Presenting with Additional Manifestations Resembling Alternating Hemiplegia of Childhood-Expanding the Phenotype of a Recently Reported Condition.

CASE: We report a 15-year-old Indian girl born to a consanguineous couple, who presented with epilepsy, developmental delay, neuroregression, and episodes of alternating hemiparesis. In addition, she had one episode of rhabdomyolysis at the age of 7 years. Extensive genetic and metabolic work up through the years was unrevealing. Eventually a trio whole exome sequencing (WES) revealed homozygous single nucleotide variants in TANGO2 gene. DISCUSSION: TANGO2 related recurrent metabolic crises with encephalomyopathy and cardiac arrhythmias were described very recently and only 15 cases were reported in literature at the time of writing. Alternating hemiplegia of childhood which was seen in our patient, has not been described in previous patients with TANGO2 mutation, and thereby expands the emerging phenotypic spectrum of this novel entity. This report also reiterates the utility of WES in diagnosing newly recognized neurogenetic conditions.

Is Shunt Evaluation Useful in Children With Intraventricular Shunts With Seizures?

BACKGROUND: Seizures are a common presenting symptom to the emergency department (ED) in children with intraventricular shunts (IVS). The incidence of shunt malfunction and the yield of imaging studies in children with IVS presenting with seizures is unknown. OBJECTIVES: We assessed the utility and diagnostic yield of evaluation for shunt malfunction in patients with IVS with seizure and identified clinical predictors for shunt malfunction in these children. METHODS: We performed a retrospective review of children aged zero to 21 years of age with IVS who presented to the ED with seizure between 2011 and 2015. Demographic, clinical, laboratory and radiological data were collected. Shunt malfunction was diagnosed based on whether a shunt revision was performed during the hospitalization. RESULTS: We evaluated 408 ED visits (median age: six years [IQR: 3, 11], males 61.5%) for IVS with seizures. Few visits were for first seizure (37; 9.1%) or for status epilepticus (46 visits; 11.3%). Computerized tomography head was performed in 318 patients (95.2%), of which 32 scans (10.6%) were suggestive of shunt malfunction. A shunt series was performed in 302 (90.4%) and was suggestive of shunt malfunction in eight (2.6%) patients. Shunt malfunction was diagnosed in 40 of 408 visits (9.8%). Only a history of multiple (≥3) shunt revisions was significantly associated with shunt malfunction. There was no association between number, type, or prior history of seizures and shunt malfunction. CONCLUSION: Our study demonstrates a low yield of imaging studies for the evaluation of shunt malfunction in children with IVS with seizures, and shunt malfunction is an uncommon cause of seizures in these children.

Phase-amplitude coupling between interictal high-frequency activity and slow waves in epilepsy surgery.

OBJECTIVE: We hypothesized that the modulation index (MI), a summary measure of the strength of phase-amplitude coupling between high-frequency activity (>150 Hz) and the phase of slow waves (3-4 Hz), would serve as a useful interictal biomarker for epilepsy presurgical evaluation. METHODS: We investigated 123 patients who underwent focal cortical resection following extraoperative electrocorticography recording and had at least 1 year of postoperative follow-up. We examined whether consideration of MI would improve the prediction of postoperative seizure outcome. MI was measured at each intracranial electrode site during interictal slow-wave sleep. We compared the accuracy of prediction of patients achieving International League Against Epilepsy class 1 outcome between the full multivariate logistic regression model incorporating MI in addition to conventional clinical, seizure onset zone (SOZ), and neuroimaging variables, and the reduced logistic regression model incorporating all variables other than MI. RESULTS: Ninety patients had class 1 outcome at the time of most recent follow-up (mean follow-up = 5.7 years). The full model had a noteworthy outcome predictive ability, as reflected by regression model fit R2 of 0.409 and area under the curve (AUC) of receiver operating characteristic plot of 0.838. Incomplete resection of SOZ (P < 0.001), larger number of antiepileptic drugs at the time of surgery (P = 0.007), and larger MI in nonresected tissues relative to that in resected tissue (P = 0.020) were independently associated with a reduced probability of class 1 outcome. The reduced model had a lower predictive ability as reflected by R2 of 0.266 and AUC of 0.767. Anatomical variability in MI existed among nonepileptic electrode sites, defined as those unaffected by magnetic resonance imaging lesion, SOZ, or interictal spike discharges. With MI adjusted for anatomical variability, the full model yielded the outcome predictive ability of R2 of 0.422, AUC of 0.844, and sensitivity/specificity of 0.86/0.76. SIGNIFICANCE: MI during interictal recording may provide useful information for the prediction of postoperative seizure outcome.

Deep cerebral vein expansion with metabolic and neurocognitive recovery in Sturge-Weber syndrome.

We present longitudinal imaging data of a child with Sturge-Weber syndrome (SWS). At age 8 months, 3 weeks after initial seizures and prolonged motor deficit, MRI showed extensive right hemispheric SWS involvement with severe glucose hypometabolism on PET. She was treated with levetiracetam and aspirin. Follow-up imaging at age 29 months showed a robust interval expansion of enlarged deep medullary veins throughout the affected hemisphere along with a dramatic recovery of hemispheric metabolism and normalized neurocognitive functioning. These findings demonstrate a robust, multilobar hemispheric remodeling of deep venous collaterals that likely contributed to reversal of initial metabolic and neurocognitive deficits.

More than meets the eye: infant presenting with hypoxic ischaemic encephalopathy.

We report a newborn infant who presented with poor Apgar scores and umbilical artery acidosis leading to the diagnosis of hypoxic ischaemic encephalopathy. During the course of the infant's hospitalisation, subsequent workup revealed an underlying genetic cause that masqueraded as hypoxic ischaemic encephalopathy.

Presurgical language mapping using event-related high-gamma activity: The Detroit procedure.

A number of investigators have reported that event-related augmentation of high-gamma activity at 70-110 Hz on electrocorticography (ECoG) can localize functionally-important brain regions in children and adults who undergo epilepsy surgery. The advantages of ECoG-based language mapping over the gold-standard stimulation include: (i) lack of stimulation-induced seizures, (ii) better sensitivity of localization of language areas in young children, and (iii) shorter patient participant time. Despite its potential utility, ECoG-based language mapping is far less commonly practiced than stimulation mapping. Here, we have provided video presentations to explain, point-by-point, our own hardware setting and time-frequency analysis procedures. We also have provided standardized auditory stimuli, in multiple languages, ready to be used for ECoG-based language mapping. Finally, we discussed the technical aspects of ECoG-based mapping, including its pitfalls, to facilitate appropriate interpretation of the data.

Vertical gaze palsy due to medication error.

We present a teenage boy with recent onset of seizures, who was erroneously treated with a large dose of an antiseizure medication as a result of drug mix-up. The ensuing drug toxicity caused vertical gaze palsy, an unusual manifestation related to overdose of the agent. Timely recognition of the error and discontinuation of the drug resulted in complete recovery to baseline.

Epidemiology of Invasive Fungal Infections at Two Tertiary Care Neonatal Intensive Care Units Over a 12-Year Period (2000-2011).

We conducted a retrospective review of 168 patients with invasive fungal infections from January 2000 to December 2011 in 2 neonatal intensive care units. Patients with Candida bloodstream infection (BSI, n = 152) were further analyzed. C albicans was the most common species overall (47%); however, there was an increase in non-albicans sp from 2006 to 2011. Candida BSI clearance rates were lower in extremely low birth weight infants (77% vs 93%, P = .01) and in patients with C albicans infections (77% vs 91%, P = .01). Clearance rates improved from 2000 to 2005 (70% - 90%) to 2006 to 2011 (86% -100%). Combination antifungal use increased during the later years (73% vs 49%, P < .05) and in patients with end-organ dissemination (83% vs 54%, P < .05). We concluded that extremely low birth weight infants and C albicans infection are factors associated with nonclearance of Candida BSI. Successful clearance of Candida BSI improved in 2006 to 2011, perhaps due to increase in non-albicans species and the use of combination antifungals.