Childhood Absence Epilepsy- Electroclinical Profile and Prevalence of Attention-Deficit/Hyperactivity Disorder Among a Cohort of 47 Children.

BACKGROUND: We aimed to find the proportion of attention-deficit/hyperactivity disorder (ADHD) among children with childhood absence epilepsy (CAE) and to describe their electroclinical features. METHODS: Video electroencephalography (EEG) was performed on 47 children who fulfilled International League Against Epilepsy criteria for CAE. These children were also assessed for the presence of ADHD. RESULTS: Of the 47 children, 27 (57%) met criteria for the diagnosis of ADHD. Majority (74%) of them had inattentive type of ADHD. Age at onset of absences ranged from three to 12 years (mean 7.2 ± 2.47). We analyzed 219 seizures (154 electroclinical and 65 electrographic). The average seizure duration was 7.1 seconds (range 1 to 38 [S.D. 5.81]). Of the 154 clinical absences, ictal discharges were less than or equal to two seconds in nine of 154 (5.8%); greater than two to less than or equal to four seconds in 33 of 154 (21.4%), and longer than 20 seconds in 11 of 154 (7%). The longest duration of ictal discharge recorded was 38 seconds, and the shortest duration was one second. The onset of ictal discharge had a "lead in" focus in 81% (177 of 219). CONCLUSIONS: The proportion of ADHD among children with CAE is high. A "lead in" focus of the generalized ictal discharges was observed frequently, lending support to the theory that the origin of seizure discharges in CAE is indeed cortical. The shortest ictal discharge recorded was one second.

Long-term survival and factors associated with mortality among children with infantile epileptic spasms syndrome - A retrospective cohort study.

BACKGROUND AND OBJECTIVES: The existing literature indicates a higher risk of mortality among children with Infantile epileptic spasms syndrome (IESS). Our aim was to find the mortality pattern and factors that affect survival among children with IESS. METHODS: Children with IESS who had age of onset between one month and 24 months were included. The primary outcome was survival. We used Kaplan-Meier estimates for survival analysis and Cox regression analyses to evaluate possible factors associated with mortality. RESULTS: During the follow-up period (120 months), 19/160 children (11.9%) expired. Three children expired in the first week after initiation of ACTH. There were six deaths (3.8%; 31.6% of deaths), within two years. Clinical findings and laboratory investigations revealed the cause of death to be severe pneumonia in ten children. Three died of severe sepsis. Four died due to metabolic crisis and two children died due to probable Sudden unexpected death in epilepsy (SUDEP). On multivariable analysis, mortality was predicted by 'presence of seizures other than spasms' and an inborn error of metabolism (IEM) as the underlying cause. None of the children in the idiopathic group died. CONCLUSION: Survival in our single center cohort with IESS was good in comparison to previous studies. Considering that pneumonia and sepsis were the most common cause of mortality that we detected, steps for prevention of sepsis might be worth considering in these children. Presence of seizures other than epileptic spasms, and an IEM should prompt the physician to let the family know that risk of mortality is high.

Factors Related to Long Term Motor, Behavioral, and Scholastic Outcome in Children with Acute Disseminated Encephalomyelitis.

OBJECTIVE: We studied the long-term outcome of Acute disseminated encephalomyelitis (ADEM). METHODS: We performed a retrospective cohort study among children diagnosed with ADEM (fulfilling IPMSSG criteria). Major outcome variables were motor deficit, scholastic underperformance, and behavioral abnormality. RESULTS: The inclusion criteria were fulfilled by 102 children. Three died in hospital. The follow-up ranged from one to 10 years (median 4 years). Motor deficit was seen in 17(17.2%), attention deficit in 25 (25.3%), behavioral abnormality in 13(13.1%), persistent seizures in seven (7%) invididuals and poor learning skills in 22 (22.2%). Recurrence of demyelination occurred in seven (7.1%). Two individuals had a recurrent demyelinating disorder (a chronic relapsing demyelinating disorder) that could not be classified as multiple sclerosis (MS), two had ADEM with sequential optic neuritis and three had multiphasic ADEM. At follow-up, the mean (SD) modified Rankin Scale (mRS) score was 0.556 (1.36) and Expanded Disability Status Scale score was 1.71(2.22). On multivariate analysis, the mRS score at discharge (p<0.01) and thalamic lesions on magnetic resonance imaging (MRI) (p<0.01) were associated with motor sequelae; poor learning skills with ADEM with concomitant polyneuropathy (p<0.02); and behavioral abnormality with tumefactive demyelination (p<0.02). CONCLUSIONS: Children who had ADEM may have motor or cognitive sequelae, seizures or recurrent demyelinating events on follow-up. We identified a few risk factors for these sequelae. Factors that affected outcome on discharge from hospital did not affect chances of having long-term sequelae. On follow-up, none of the children fulfilled the diagnostic criteria for MS, suggesting that the chance of conversion of ADEM to MS is less likely.

Amantadine for the Treatment of Refractory Absence Seizures in Children.

INTRODUCTION: Childhood epilepsy is a generalized epilepsy syndrome with a favorable response to antiepileptic drugs; however, a small percentage of typical absence seizures remain refractory to drugs. We studied the safety and efficacy of amantadine in children with refractory absence seizures. MATERIALS AND METHODS: Of 48 children with typical absence seizures attending the outpatient department of a tertiary care neurological center over a period of 3 years from July 2013 to June 2016, 4 children who were refractory to standard treatment for at least 1 year were selected and were started on amantadine 4-6 mg/kg/day, after obtaining informed consent. OBSERVATIONS: The children, aged between 7 and 14 years, had more than 10 episodes of seizures per day in spite of polytherapy with valproate, lamotrigine, clonazepam, levetiracetam, and topiramate in various combinations. Electrographically, all showed the typical generalized 3 Hz spike wave discharges activated by hyperventilation. All the children became seizure free within 1 week after starting amantadine, and there was improvement in their school performance. The children continue to remain seizure free for 6-30 months now. No significant adverse effects were observed on addition of amantadine. DISCUSSION: Amantadine can be tried as a safe add-on drug for children with absence epilepsy refractory to multiple drugs. Further multicenter trials may be needed to prove its effectiveness, as the numbers are small.

Vitamin D Deficiency in Ambulant Children on Carbamazepine or Sodium Valproate Monotherapy.

OBJECTIVE: To assess the effect of monotherapy with Carbamazepine (CBZ) and Sodium valproate (VPA) on serum 25-OH Vitamin D levels in children with epilepsy compared to controls. DESIGN: Cross-sectional study. SETTING: Outpatient department of a tertiary-care Pediatric Neurology centre, and a nearby day-care centre and school. STUDY PERIOD: June 2012 to May 2013. PARTICIPANTS: Children with epilepsy aged 2 to 13 years on monotherapy with CBZ (n=28) or VPA (n=28) for at least 6 months; 109 age-matched controls from a nearby day-care centre and school. RESULTS: The median (IQR) values of 25 (OH) vitamin D was 18.0 ng/mL (13.7-27.3), 21.35 ng/mL (16.4 -25.2) and 30.5 ng/mL (19.1-43.7) in CBZ, VPA and control group, respectively (P= 0.008). 60.7% of patients in CBZ group and 35.7 % in VPA group had low 25 (OH) D levels (%20 ng/mL) compared to 27.8% in controls (P=0.001).The serum alkaline phosphatase level was higher in children on carbamazepine therapy (P=0.001) than controls. CONCLUSION: This study identifies significant risk of vitamin D deficiency in ambulant children with epilepsy on monotherapy with CBZ or VPA.

Short term outcome of ADEM: Results from a retrospective cohort study from South India.

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM), an immune mediated inflammatory disease is common in children. The profile and immediate outcome of children hospitalized with ADEM is scarce in the available literature. OBJECTIVES: We aimed to study the clinical profile of children with ADEM and to look for prognostic factors for outcome at discharge from hospital METHODS: We chose a retrospective cohort study of all children diagnosed with ADEM at our institution between January 2006 and December 2015, and they were evaluated, after excluding other diagnoses when they were summoned for a follow up visit. The major outcome variables were the modified Rankin Scale (mRS), the Kurtzke Expanded Disability Status Scale (EDSS) and the Glasgow outcome score (GOS) RESULTS: There were 102 children (with a mean follow up of 4.81 ± 2.78 years) and mean age at presentation, 6.16 ± 3.1 years. Pyramidal signs, ataxia, fever at onset, brain stem signs, seizures, myelitis and headache were the commoner clinical manifestations. Movement disorders particularly disabling tremor was seen in 12%. Only 52% had MRI lesions confined to supratentorial region, with 20% having thalamic lesions, 14% with corpus callosal lesions and 28% with brain stem hyperintensities. Three patients expired during the acute stage of the disease, the rest recovering with a mean mRS score of 1.92 ± 1.7 and EDSS score of 2.96 ± 3.05. On multivariable regression analysis, using mRS, presence of fever at admission, myelopathy with a definite sensory level and ventilator associated pneumonia were associated with a bad outcome. Using EDSS score (multivariable regression), presence of myelopathy with a definite sensory level and coma were associated with a bad outcome. Using GOS score (multivariable regression), presence of myelitis with a definite sensory level, signs of meningeal irritation and encephalomyeloradiculoneuropathy type of ADEM were associated with a bad outcome and headache with a good prognosis. The mean of the number of hours of altered sensorium and the mean duration of hospital stay in days had a significant association using the mRS, EDSS score and GOS. CONCLUSION: This study shows a profile of ADEM in South Indian children at admission and at discharge from hospital. ADEM has a good immediate outcome though death during the nadir of disease has been recorded in this study and in the literature and effort should be taken for optimal life support for these children who would have a good outcome if life support is successful. We have been able to show that, presence of myelopathy, the mean number of hours of altered sensorium and the mean duration of hospital stay were associated with a bad prognosis using three different outcome scales. Fever at admission, ventilator associated pneumonia, more profound altered sensorium at nadir of disease, signs of meningeal irritation at presentation and lower motor neuron involvement also, during the course of disease were associated with an immediate bad outcome using one of the outcome scores used in our study. Future studies should also address the question of why children with myelopathy, signs of lower motor involvement and fever at onset have a bad immediate outcome.

Neurometabolic disorder with microcephaly, dystonia, and central cyanosis masquerading as cerebral palsy.

Many neurodegenerative diseases can be misdiagnosed as cerebral palsy. The correct diagnosis is reached when the condition recurs in families or when there are specific clinical signs. The clinical and imaging features of 3 children, from 2 unrelated families, presenting with global developmental delay and dystonia are described, in whom the presence of cyanosis and methemoglobinemia confirmed the diagnosis of recessive hereditary methemoglobinemia type 2. Magnetic resonance imaging showed significant cerebellar atrophy in 2 of the 3 babies. In dark-skinned children, this condition is underdiagnosed, as mild cyanosis is difficult to detect. Screening for methemoglobinemia in children with dystonia, microcephaly, and progressive cerebellar atrophy can be helpful in identifying more cases. As there is no curative treatment for this autosomal recessive condition, the exact diagnosis offers the best chance for prenatal screening, by detecting deficient NADH--cytochrome b5 reductase enzyme activity or by identifying the specific mutation in cultured amniotic fluid cells.