Evaluation of auditory spectral resolution abilities in children with benign epilepsy with centrotemporal spikes using spectral temporally modulated ripple test.

PURPOSE: Spectral resolution is imperative for complex listening tasks such as understanding speech in the presence of background noise and has a significant role in children, particularly classroom learning. The present study evaluated the auditory spectral resolution abilities of children with Benign epilepsy with centrotemporal spikes (BECTS). METHOD: This cross-sectional study conducted from August 2017 to March 2020 recruited 23 children with clinical and electrographic features consistent with BECTS as cases. Fifteen age and sex matched typically developing children (TDC) were taken as controls. Spectral resolution abilities were evaluated using the recently developed Spectral temporally modulated Ripple test (SMRT). RESULTS: The mean age of the cases was 10.63 ±â€¯1.91 years with a slight male preponderance (69%). The mean (±SD) SMRT thresholds in the cases and controls were 5.90 (±1.91) and 7.21 (±1.03) respectively. The auditory spectral resolution threshold measured by SMRT in children with BECTS was observed to be significantly lower when compared to the controls (p of 0.021). CONCLUSION: Children with BECTS have a lower spectral resolution threshold by SMRT.

Intensive Care Unit-Acquired Weakness in Children: A Prospective Observational Study Using Simplified Serial Electrophysiological Testing (PEDCIMP Study).

BACKGROUND: To study the incidence and time of onset of intensive care unit-acquired weakness in a prospective cohort of children (2-12 years) by serial simplified electrophysiological assessment (Pediatric Critical Illness Myopathy Polyneuropathy study, PEDCIMP). METHODS: A single-center, prospective cohort study (Trial Registry Number: NCT02763709; PEDCIMP2016) was conducted at the pediatric intensive care unit of a tertiary care hospital in North India. A complete electrophysiological evaluation (4 motor nerves and 2 sensory nerves) was performed at baseline in children (2-12 years) admitted to the ICU with a pediatric risk of mortality (PRISM) of > 20 with more than 24-h stay. Following the entry evaluation, a minimal alternate day simplified electrophysiological testing of the unilateral common peroneal nerve and the sural nerve was assessed. A 25% reduction in compound muscle action potential (CMAP) and sensory nerve action potential from baseline was considered significant for ICUAW and was confirmed by complete electrophysiological re-evaluation. RESULTS: Of the total 481 children assessed for eligibility, 97 were enrolled. The median age of the cohort was 7 years. Sepsis (81%); need for vasoactive support (43%); multiorgan dysfunction (26%) were the common reasons for admission. Of the 433 eligible patient ICU days, 380 electrophysiological observations were done. A significant decrease of > 25% in CMAP of common peroneal nerve was not detected in any of the 380 observations. However, two children unfit for inclusion were diagnosed with ICUAW during the study period. CONCLUSIONS: Children admitted with PRISM > 20 have a very low incidence of intensive care unit-acquired weakness by serial clinical and abbreviated electrophysiological evaluation.

Evaluation of Optic Nerve Sheath Diameter and Transcranial Doppler As Noninvasive Tools to Detect Raised Intracranial Pressure in Children.

OBJECTIVES: To compare the diagnostic accuracy of the ultrasonography-guided optic nerve sheath diameter with transcranial Doppler-guided middle cerebral artery flow indices against the gold standard invasive intraparenchymal intracranial pressure values in children. DESIGN: A single-center prospective cohort study. SETTING: PICU of a tertiary care teaching hospital in North India. PATIENTS: Eligible children (2-12 yr) are admitted to ICU and are undergoing intracranial pressure monitoring using an intraparenchymal catheter. Observations with a parallel measured intracranial pressure greater than or equal to 20 mm Hg were included as case-observations. Children with an invasive intracranial pressure of less than or equal to 15 mm Hg were taken as neurologic-control-observations and healthy children served as healthy-control-observations. INTERVENTIONS: The horizontal and vertical diameters of the optic nerves were measured, and averages were calculated and compared. Middle cerebral artery flow indices (pulsatility index and resistive index) were measured bilaterally and averages were calculated and compared in the three groups. Twenty-two measurements of optic nerve sheath diameter were assessed by two different observers in quick succession for interrater reliability. MEASUREMENTS AND MAIN RESULTS: A total of 148 observations were performed in 30 children. Four observations were excluded (intracranial pressure between 16 and 19 mm Hg). Of the 144 observations, 106 were case-observations and 38 were neurologic-control-observations. Additional 66 observations were healthy-control-observations. The mean optic nerve sheath diameter was 5.71 ± 0.57 mm in the case-observations group, 4.21 ± 0.66 mm in the neurologic-control-observations group, and 3.71 ± 0.27 mm in the healthy-control-observations group (p < 0.001 for case-observations vs neurologic-control-observations/healthy-control-observations). The mean pulsatility index in case-observations was 0.92 ± 0.41 compared with controls 0.79 ± 0.22 (p = 0.005) and the mean resistive index was 0.56 ± 0.13 in case-observations compared with 0.51 ± 0.09 (p = 0.007) in controls (neurologic-control-observations and healthy-control-observations). For the raised intracranial pressure defined by intracranial pressure greater than or equal to 20 mm Hg, the area under the curve for optic nerve sheath diameter was 0.976, while it was 0.571 for pulsatility index and 0.579 for resistive index. Furthermore, the optic nerve sheath diameter cutoff of 4.0 mm had 98% sensitivity and 75% specificity for raised intracranial pressure, while the pulsatility index value of 0.51 had 89% sensitivity and 10% specificity by middle cerebral artery flow studies. The sensitivity and specificity of 0.40 resistive index value in the raised intracranial pressure were 88% and 11%, respectively. Kendall correlation coefficient between intracranial pressure and optic nerve sheath diameter, pulsatility index, and resistive index was 0.461, 0.148, and 0.148, respectively. The Pearson correlation coefficient between two observers for optic nerve sheath diameter, pulsatility index, and resistive index was 0.98, 0.914, and 0.833, respectively. CONCLUSIONS: Unlike transcranial Doppler-guided middle cerebral artery flow indices, ultrasonography-guided optic nerve sheath diameter was observed to have a good diagnostic accuracy in identifying children with an intracranial pressure of greater than or equal to 20 mm Hg.

Pyridoxine Therapy: Not Just the Dose, the Duration Matters Too.

Pyridoxine-dependent epilepsy (PDE) (OMIM 266100) is an autosomal recessive disorder of lysine metabolism secondary to antiquitin deficiency. The prototypical presentation is intractable neonatal seizures that do not respond to conventional antiseizure medication but are well controlled by pyridoxine supplementation. Atypical forms account for one-third of the PDE spectrum and may escape early diagnosis. The common atypical presentations include the prenatal onset of seizures, seizures onset as delayed as 3 years of age, autism, arrested hydrocephalus, and fetal ventriculomegaly. Herein, we describe a 9-month-old child with neonatal-onset refractory seizures who failed two short trials of pyridoxine therapy and was later diagnosed with PDE by molecular studies. Regardless of the therapeutic response, a prolonged course of pyridoxine therapy is justified to identify delayed responders in infants with drug-refractory epilepsy of no apparent etiology.

Efficacy and Tolerability of Lacosamide in Lennox-Gastaut Syndrome: A Systematic Review and Meta-analysis.

Purpose Lennox-Gastaut syndrome (LGS) is one of the most difficult to treat childhood-onset epileptic encephalopathies. There is growing evidence that lacosamide is safe and efficacious in patients and adults with refractory epilepsy. However, the evidence regarding the efficacy of lacosamide in LGS is controversial so far. We aimed to evaluate the efficacy and tolerability of lacosamide in patients with LGS. Methods We conducted a systematic review on MEDLINE, EMBASE, COCHRANE CENTRAL, Google Scholar, and Web of Science, collating all available literature till July 31, 2020. The qualitative review included case reports, case series, and both controlled/uncontrolled trials as well as retrospective studies, but for determining pooled estimates, we only included studies with a sample size of 5 or more. The primary outcome was the efficacy of lacosamide in patients with LGS. Clinical variables related to efficacy and adverse events attributed to lacosamide were extracted from each publication. The pooled estimate of variables related to these parameters was performed using a random-effect model. Results Of the 68 items identified by the search, 14 were reviewed as full-text. Eleven articles including two prospective and six retrospective studies fulfilled eligibility criteria and described outcomes in 81 patients (42 adults, 39 children, 60% male, range-1.4-61 years). On average, 35.2%, 27.9%, 7.3%, and 29.4% patients had > 50% reduction, < 50% reduction, no change, and worsening of seizure frequency, respectively. Although 36% of patients had adverse events like somnolence, behavioral abnormalities including irritability, aggressiveness, nausea, tremor, memory problems, dizziness, gastrointestinal discomfort, vomiting, and weight loss, no serious adverse events were noted. Conclusion The evidence available in the current literature is not sufficient to support or refute the use of lacosamide in patients with LGS. Although it is one of the possible therapeutic options worth exploring in patients with LGS, caution is still necessary, as there are reports of worsening of seizure frequency in some patients.

Prevalence of peripheral neuropathy and associated risk factors in children with type 1 diabetes.

AIM: To detect the prevalence of diabetic polyneuropathy (DPN) in children with type 1 diabetes (T1D) and to identify associated the risk factors. METHODS: This cross-sectional study evaluated children aged between 2 and 16y with T1D for ≥2 y. Detailed neurological examination, neuropathy symptom score, and nerve conduction studies were done in all children to assess nerve dysfunction. Disease-related factors were evaluated for the prediction of neuropathy. RESULTS: Sixty-six children (67% boys) were enrolled. The mean age at the time of diagnosis of T1D was 7.1 ± 2.6 years. The mean duration of diabetes was 4 ± 1.8 years. None of the patients had neuropathy on clinical examination or on the neuropathy symptom score. The prevalence of subclinical DPN was 18.2% (n = 12/66). The type of neuropathy was pure motor (n = 11, 91.6%) and mixed sensorimotor (n = 1, 8.3%). The common peroneal nerve was most commonly affected (n = 6, 50%), followed by the tibial (n = 4, 33.3%) nerve. The most common patterns of nerve involvement were mixed axonal and demyelination (n = 7, 58.3%), followed by axonal (n = 3, 25%) and demyelinating type (n = 2, 16.6%). Children with subclinical DPN had a significant reduction in velocity of tibial, common peroneal, median motor, and ulnar motor nerves; delayed latency in common peroneal, median motor, ulnar motor, and median sensory nerves compared to those without DPN (p value <0.05). A higher body mass index predicted the development of subclinical DPN (p value <0.05). CONCLUSION: Nearly one-fifth of children with T1D have subclinical neuropathy as early as two years of the disease. A higher body mass index is significantly associated with DPN. Electrophysiological studies should be performed regularly to screen for nerve dysfunction and its progression.

Cerebral sinus venous thrombosis: a rare complication of varicella infection in a 12-year-old girl.

Varicella infection can present with a variety of neurological manifestations, the most common of which are cerebellitis and encephalitis. A 12-year-old girl presented with headache, altered sensorium, blurring of vision and status epilepticus 2 weeks after she developed varicella lesions. Imaging demonstrated cerebral venous sinus thrombosis involving the left transverse sinus, sigmoid sinus and internal jugular vein with a haemorrhagic infarct in the left parieto-occipital region. Measures were taken to decrease the intracranial pressure, and she was commenced on anti-convulsants (phenytoin) and heparin infusion, following which she improved and was discharged after 2 weeks. Repeat imaging undertaken 3 months later demonstrated a resolving thrombus, and a pro-coagulant work-up at follow-up did not show any underlying pro-thrombotic state. Neurological complications post varicella are rare, with encephalitis and ataxia being the most common. Cerebral sinus venous thrombosis secondary to varicella is very rare with only one case reported in a child.

Identification of novel pathogenic variants in the GCDH gene and assessment of neurodevelopmental outcomes in 24 children with glutaric aciduria type 1.

AIM: To evaluate the pathogenic variants in GCDH gene and to assess the neurodevelopmental outcomes in children with Glutaric aciduria type 1 (GA-1). METHOD: Cross-sectional observational study between January 2019 and June 2020 in consecutive North Indian children with a clinical and biochemical suspicion of GA-1. Variants in the coding regions of GCDH gene were identified through Sanger sequencing. Neurodevelopmental and quality of life assessment was done using standardized scales. RESULTS: 24 children with GA-1 were identified. The median age at diagnosis was 12 months and the median delay in diagnosis was 3 months. Genetic analysis was done in 14 cases. It revealed 12 variants (11 missense and one nonsense) from 13 patients. Most of the pathogenic variants were in exon 9 and exon 5. Three novel variants were identified in three patients: two missense variants c.169G > A (p.Glu57Lys), c.1048T > C (p.Cys350Arg) and one nonsense variant c.331C > T (p.Lys111Ter). On neurodevelopmental assessment, majority of children with GA-1 were non ambulatory (62.5%), had limited hand skills (58.3%) and impaired communication (58.3%). Overall, poor global development was noted in 43.7%. A pre-existing developmental delay was significantly associated with impaired communication skills (p = 0.03), and the number of episodes of encephalopathy were significantly associated with impaired gross motor skill (p = 0.02). Presence of encephalopathy was significantly associated with poor performance in social emotional (p = 0.01) and cognitive (p = 0.03) domains of Developmental Profile-III scale and development of severe dystonia (p = 0.01). CONCLUSION: Our findings highlight the clinical, biochemical, radiological and genetic spectrum of GA-1 in children in North India and report the presence of novel pathogenic variations.