Arterial Ischemic Stroke-Peculiarities of Clinical Presentation and Risk Factors in Indian Children.

There are not enough recent studies on arterial ischemic stroke (AIS) in Indian children. We retrospectively reviewed data on 95 children (69 boys), aged 3 months to 17 years, with AIS. Focal signs were noted in 84 (88%) with hemiparesis in 72 (76%). Diffuse signs were present in 33 (35%) with fever in 22 (23%), altered mental status in 20 (21%), and headache in 12 (13%). Seizures occurred in 29 (31%) children. Arteriopathy was observed in 57 (60%) children with mineralizing lenticulostriate vasculopathy (mLSV) in 22 (23%) being the most common, followed by moyamoya in 14 (15%), arterial dissection in 9 (10%), and focal cerebral arteriopathy (FCA) in 8 (8%). Preceding head/neck trauma was present in 27 (28%) children: 23 had minor head trauma (MHT), 3 neck trauma, and 1 unspecified. Other common risk factors (RFs) were iron deficiency in 10 children, homocysteinemia in 8 children, and tuberculous meningitis in 5 children. Complete or nearly complete recovery occurred in 42 (44%). Nine children developed epilepsy and five cognitive and language disability. Stroke recurrences occurred in nine children. Overall, arteriopathies accounted for majority of the cases of childhood AIS in our study with mLSV and moyamoya being the most frequent. Compared with data from Western countries, FCAs, postvaricella arteriopathy, and arterial dissections were less common. Of the nonarteriopathic RFs, MHT, iron deficiency, homocysteinemia, and neuroinfections were most frequent in our cohort in contrast to cardioembolic diseases and inherited procoagulant conditions, which are common in developed countries.

Epilepsy knowledge, attitudes, and practices among primary healthcare providers in an Indian district.

INTRODUCTION: Scaling up the involvement of primary care providers in epilepsy management in low- and middle-income countries (LMICs) requires an understanding of their epilepsy knowledge, attitudes, and practices (KAP). AIM: The aim of the study was to document levels of knowledge about, attitudes towards, and practices regarding epilepsy among different ranks of primary healthcare providers in a North-Western Indian district. METHODS: The survey included government medical officers (MOs), auxiliary nurse midwives (ANMs), and accredited social health activists (ASHAs). They were administered a specially designed KAP questionnaire. Responses were analyzed according to rank. RESULTS: The survey showed that nearly 10% of ANMs and almost a fifth of ASHAs had never heard about epilepsy. A quarter of MOs and over two-thirds of ANMs and ASHAs had never provided care to someone with epilepsy. There were significant differences in the levels of knowledge between the three groups of workers. CONCLUSIONS: Closing the huge gaps in KAP by educating primary care and community health workers about epilepsy should be a priority before engaging them in the epilepsy care delivery.

Dermatologic findings of vitamin B12 deficiency in infants.

BACKGROUND/OBJECTIVES: Vitamin B12 deficiency in infants is uncommonly reported from developed countries and generally lacks dermatologic manifestations. On the contrary, infantile vitamin B12 deficiency is common in India and cutaneous manifestations are a constant feature, although often overshadowed by neurologic and hematological manifestations. The aim of this study was to describe the skin changes of vitamin B12 deficiency in infants. MATERIALS AND METHODS: A retrospective chart review of vitamin B12 deficient infants for clinical and laboratory parameters was performed and data analyzed. RESULTS: Forty-three infants, 30 boys and 13 girls, aged 4 to 27 months, with vitamin B12 deficiency were identified. Skin hyperpigmentation was present in 41 infants; it was localized to the dorsa of hands and feet in 26. Fifteen infants had generalized hyperpigmentation; 10 had a reticulate pattern, and 5 had a homogeneous pattern. Brown and sparse scalp hair were present in all. Glossitis was seen in 5 infants and cheilitis in 3. Of the 32 infants who underwent laboratory investigations, 28 had anemia and 21 macrocytosis. Serum vitamin B12 was measured in 30 infants; it was low in 19. Of the 11 with normal serum vitamin B12 , 9 had received vitamin B12 before referral but had macrocytosis and low maternal serum vitamin B12 . The infants were treated with vitamin B12 . Skin pigmentation and mucosal changes resolved completely by 3-4 weeks, but hair changes were slower to reverse. CONCLUSION: Cutaneous findings are a common feature of vitamin B12 deficiency in Indian infants and resolve with treatment.

Mineralizing Lenticulostriate Vasculopathy: An Emerging Risk Factor for Basal Ganglia Stroke After Minor Head Trauma in Young Children.

Mineralizing lenticulostriate vasculopathy is a well-recognized risk factor for basal ganglia stroke after minor head trauma in infants and young children; it is diagnosed on head computed tomography by the presence of basal ganglia calcification, seen as punctate hyperdensities on axial and linear hyperdensities on reconstructed coronal and sagittal images. In children with anterior fontanel window, its presence is suggested by branching hyperechogenic stripes in the basal ganglia region on cranial ultrasound. Brain magnetic resonance imaging, including susceptibility-weighted sequences and brain magnetic resonance angiography, fail to detect calcification or vascular abnormalities. Although its etiology remains unknown, mineralizing lenticulostriate vasculopathy is considered to represent end-stage pathology of lenticulostriate vasculopathy, a neonatal radiographic condition detected during routine neonatal cranial ultrasonographic examination and represents nonspecific finding associated with a multitude of etiologies. The significance of mineralizing lenticulostriate vasculopathy lies in the fact that it has emerged as one of the most common risk factors for basal ganglia stroke in Indian children, accounting for one-fourth to one-half of all causes of stroke in some studies. The outcome of stroke in children with mineralizing lenticulostriate vasculopathy appears to be favorable with the majority achieving complete or nearly complete recovery of their motor functions. Stroke recurrence following repeat head trauma is seen in a small proportion of children despite aspirin treatment.

Epileptic Spasms During Recovery From Nutritional Infantile Vitamin B12 Deficiency.

Development of epileptic spasms in infants with vitamin B12 deficiency is uncommon. In some cases, infants presenting with epileptic spasms have been found to have concurrent vitamin B12 deficiency. Treatment with vitamin B12 and adrenocorticotropic hormone (ACTH) resulted in resolution of epileptic spasms. In others, epileptic spasms have developed during recovery from vitamin B12 deficiency. Treatment with ACTH or other seizure medications resulted in resolution of epileptic spasms, although response has been less predictable. We describe three infants who initially presented with clinical and laboratory features of vitamin B12 deficiency. Treatment with vitamin B12 resulted in rapid resolution of symptoms. However, recovery was interrupted by the development of epileptic spasms. All infants showed hypsarrhythmia on electroencephalography. Treatment with prednisolone, with or without other antiseizure medications, resulted in slow resolution of spasms. Cognitive and language delays were noted in two infants. Epileptic spasms may supervene during recovery from vitamin B12 deficiency affecting outcomes.

ITPA-associated developmental and epileptic encephalopathy: characteristic neuroradiological features with novel clinical and biochemical findings.

Developmental and epileptic encephalopathies (DEE) in children have an everexpanding range of rare causes. Mutations in ITPA have been recently described as causative of DEE, but only a small number of patients have been reported so far. We describe two Indian children with novel variants in the ITPA gene. Both patients had characteristic, previously described, neuroradiological findings that helped us suspect this condition even before genetic evaluation. In addition, we present new and rarely reported clinical findings associated with this condition: migrating partial epilepsy, fever-triggered seizures, movement disorder including oculogyria and dystonic tremor. One of the patients also had high cerebrospinal fluid glycine levels. Both patients had drug-responsive epilepsy, in contrast to drug-resistant seizures in previously reported patients. These patients reiterate the utility of awareness of specific neuroradiological findings and subsequent genetic evaluation to help make a precise diagnosis. Our report also extends the clinical spectrum and provides insight into possible biochemical causes for the neuroimaging findings seen in this condition.

A cluster-randomized trial comparing home-based primary health care and usual clinic care for epilepsy in a resource-limited country.

OBJECTIVE: To ascertain whether home-based care with community and primary healthcare workers' support improves adherence to antiseizure medications, seizure control, and quality of life over routine clinic-based care in community samples of people with epilepsy in a resource-poor country. METHODS: Participants included consenting individuals with active epilepsy identified in a population survey in impoverished communities. The intervention included antiseizure medication provision, adherence reinforcement and epilepsy self- and stigma management guidance provided by a primary health care-equivalent worker. We compared the intervention group to a routine clinic-based care group in a cluster-randomized trial lasting 24 months. The primary outcome was antiseizure medication adherence, appraised from monthly pill counts. Seizure outcomes were assessed by monthly seizure aggregates and time to first seizure and impact by the Personal Impact of Epilepsy scale. RESULTS: Enrolment began on September 25, 2017 and was complete by July 24, 2018. Twenty-four clusters, each comprising ten people with epilepsy, were randomized to either home- or clinic-care. Home-care recipients were more likely to have used up their monthly-dispensed epilepsy medicine stock (regression coefficient: 0.585; 95% confidence intervals, 0.289-0.881; P = 0.001) and had fewer seizures (regression coefficient: -2.060; 95%CI, -3.335 to -0.785; P = 0.002). More people from clinic-care (n = 44; 37%) than home-care (n = 23; 19%) exited the trial (P = 0.003). The time to first seizure, adverse effects and the personal impact of epilepsy were similar in the two arms. SIGNIFICANCE: Home care for epilepsy compared to clinic care in resource-limited communities improves medication adherence and seizure outcomes and reduces the secondary epilepsy treatment gap.

Early-onset childhood absence epilepsy: is it a distinct entity?

Childhood absence epilepsy (CAE) typically starts between four and seven years of age. Onset before three years is rare and has not been previously reported from North America. We retrospectively reviewed the electroencephalography laboratory database and paediatric neurology clinic records (from January 2000 to June 2009) at our institution in order to identify patients with absence seizures beginning before age three. Information was collected for age, gender, neurodevelopment, antiepileptic drugs (AEDs) used, seizure control, follow-up, and side effects. Of 12 patients identified, mean age at onset was 20.5 months (range: 11 months to two years; follow-up: six months to 11 years). Seven of 12 patients had normal neurodevelopment and five had speech delay. Four patients were seizure-free without AEDs, three were seizure-free with a single AED, and five still had seizures with multiple AEDs. Three patients had recurrences after medication withdrawal. Other previously published series have identified better seizure control than that reported here, however, 16% of the 130 patients so far documented are reported to have poorly controlled epilepsy, indicating that early-onset CAE is not a homogeneous condition. The debate as to whether early-onset CAE is a distinct epilepsy syndrome therefore continues. We believe that early-onset CAE may be a distinct epilepsy syndrome, with some features that overlap with those of typical CAE, as well as unique distinguishing features. Large prospective multicentric studies would be necessary to definitely resolve this matter.

Osteomalacic Myopathy in Children and Adolescents with Vitamin-D Deficiency.

BACKGROUND: Osteomalacic myopathy secondary to vitamin-D deficiency is an under-recognized cause of muscle weakness in children and adolescents. AIM: To describe a cohort of children and adolescents with osteomalacic myopathy. SETTINGS AND DESIGN: Pediatric neurology unit of a tertiary care hospital. METHODS AND MATERIAL: Charts of children and adolescents with osteomalacic myopathy were retrospectively reviewed for demographics, clinical presentation, laboratory investigations, and treatment response. Diagnosis of vitamin-D deficiency was made on the basis of a combination of clinical, biochemical, and radiographic findings. Response to treatment with vitamin-D confirmed vitamin-D deficiency as the cause of myopathic symptoms. RESULTS: Twenty-six children-15 girls and 11 boys aged between 20 months and 19 years-with osteomalacic myopathy were identified. Fifteen (58%) children were between 10 years and 19 years of age. Twenty-one (81%) children presented with myopathic symptoms of progressive walking difficulty, with eventual loss of ambulation in six. Four children came to attention through hypocalcemic seizures. One nonambulatory child with cerebral palsy presented with loss of previously attained ability to roll over and sit. All children had proximal muscle weakness on examination. Fifteen (58%) children had clinical signs of rickets. All the children who underwent biochemical (n = 24) and radiographic (n = 16) investigations had results consistent with vitamin-D deficiency. Only in one child, the diagnosis of osteomalacic myopathy was made on the basis of clinical findings. Response to vitamin D was uniformly good. CONCLUSIONS: Vitamin-D deficiency should be considered in the differential diagnosis of proximal myopathy in children and adolescents.

Clinical characteristics of epilepsy in resource-limited communities in Punjab, Northwest India.

OBJECTIVES: To describe clinical characteristics of a community-based epilepsy cohort from resource-limited communities in Punjab, Northwest India. METHODS: The cohort was gathered following a two-stage screening survey. We cross-sectionally examined and followed up the cohort for one year. A panel of neurologists assigned seizure types, syndromes, and putative etiologies and categorized drug responsiveness. RESULTS: The cohort of 240 included 161 (67.1%) men, 109 (45.4%) illiterates and 149 (62.1%) unemployed. Current age was >18 years in 155 (64.6%) but age at epilepsy onset was <18 years in 173 (72.1%). Epilepsies due to structural and metabolic causes were diagnosed in 99 (41.3%), but syndromic assignments were not possible in 97 (40.4%). After one year, drug-resistant epilepsy was established in 74 (30.8%). Perinatal events (n = 35; 14.6%) followed by CNS infections (n = 32; 13.3%) and traumatic brain injury (n = 12; 5.0%) were common risk factors. Most of those with CNS infections (n = 19; 63.3%), perinatal antecedents (n = 23; 76.7%), and other acquired risk factors (n = 27; 90.0%) presented with epilepsy due to structural and metabolic causes. Perinatal events were the putative etiology for nearly 40.7% of generalized epilepsies due to structural and metabolic causes and 28.2% of all epilepsies with onset <10 years. SIGNIFICANCE: Existing classifications schemes should be better suited to field conditions in resource-limited communities in low- and middle-income countries. The finding of drug-resistant epilepsy in nearly at least a third in a community-based sample underscores an unmet need for enhancing services for this segment within healthcare systems. Perinatal events, CNS infections, and head injury account for a third of all epilepsies and hence preventative interventions focusing on these epilepsy risk factors should be stepped up.

Antiepileptic Drug Prices, Availability and Affordability in a Resource-Limited Setting.

BACKGROUND: The availability and affordability of antiepileptic drugs (AEDs) are critical to the success of public health initiatives enabling care for people with epilepsy in the community. OBJECTIVE: To pilot survey the availability and affordability of AEDs in the community. METHODS: Field workers used standard WHO-Health Action International approaches and collected data on the availability of, and maximum retail prices of originator brands and least price generics of AEDs in 46 randomly selected public (n = 29), private (n = 8), and charitable (n = 9) pharmacy outlets. Median price ratios were computed apropos international reference prices of corresponding medications and affordability gauged with reference to daily wage of lowest paid worker. RESULTS: Only 10 outlets (7 - private, 3 - public, and none - charitable) stocked at least one essential AED. Median price ratios varied between 1.1 and 1.5 essentially reflecting the difference between the least price generics and originator brands. Of note, carbamazepine-retard, 200 mg put up the slightest difference in prices of originator and least price generic brands and also was the most affordable AED. CONCLUSIONS: The availability and affordability of most AEDs were poor and hence, this needs to be studied on a wider scale and thereafter efforts to improve both the availability and affordability are desirable in order to address the huge treatment gap for epilepsy in India.

Sleep study abnormalities in children with attention deficit hyperactivity disorder.

The study objective was to describe polysomnographic findings in children with attention deficit hyperactivity disorder (ADHD) with diverse sleep problems. Polysomnographic data were retrospectively analyzed for 33 children (age 3-16 years) with ADHD who had sleep studies performed for diverse sleep complaints. Eight patients (24%) had obstructive sleep apnea, 10 (30%) had periodic limb movements of sleep, 8 (24%) had upper airway resistance syndrome, and 5 (15%) had obstructive hypoventilation. The ADHD group showed decreased sleep efficiency, increased arousal index, increased wake after sleep onset, decreased oxygen saturation nadir, and increased snoring, compared with control subjects. Compared with ADHD children without sleep disordered breathing, those who had sleep disordered breathing were significantly more obese and had more sleep architectural abnormalities (including increased sleep latency, increased rapid eye movement latency, increased wake after sleep onset, and increased arousal index with more oxygen desaturations), although total sleep time and sleep efficiency were not significantly different. Sleep disordered breathing and periodic limb movements of sleep appear to be common among children with ADHD who have symptoms of disturbed sleep.

A home-based, primary-care model for epilepsy care in India: Basis and design.

OBJECTIVES: A cluster-randomized trial of home-based care using primary-care resources for people with epilepsy has been set up to optimize epilepsy care in resource-limited communities in low- and middle-income countries. The primary aim is to determine whether treatment adherence to antiepileptic drugs is better with home-based care or with routine clinic-based care. The secondary aims are to compare the effects of the two care pathways on seizure control and quality of life. METHODS: The home-based intervention comprises epilepsy medication provision, adherence reinforcement, and epilepsy self-management and stigma management guidance provided by an auxiliary nurse-midwife equivalent. The experimental group will be compared to a routine clinic-based care group using a cluster-randomized design in which the unit of analysis is a cluster of 10 people with epilepsy residing in an area cared for by a single accredited government grass-roots health care worker. The primary outcome is treatment adherence as measured by monthly tablet counts supplemented by two self-completed questionnaires. The secondary outcomes include monthly seizure frequency, time to first seizure (in days) after enrollment, proportion of patients experiencing seizure freedom for the duration of the study, and quality of life measured by the "Personal Impact of Epilepsy Scale," all assessed by an independent study nurse. RESULTS: The screening phase and neurologic evaluations and randomizations have been recently completed and follow-up is underway. SIGNIFICANCE: The results of the trial are likely to have substantial bearing on the development of governmental policies and strategies to provide coverage and care for patients with epilepsy in resource-limited countries.

Spectrum of polysomnographic abnormalities in children with epilepsy.

This study sought to evaluate polysomnographic abnormalities in a cohort of 40 children with epilepsy who underwent a sleep study because of various sleep complaints. Retrospective analyses included polysomnographic variables, antiepileptic drugs, type of epilepsy, and seizure control. The subgroup with epilepsy and obstructive sleep apnea syndrome was compared with 11 children who manifested uncomplicated obstructive sleep apnea syndrome. Thirty-three patients (83%) exhibited snoring (42.5%), sleep-disordered breathing (obstructive hypoventilation, 12.5%; obstructive sleep apnea, 20%; and upper-airway resistance syndrome, 7.5%), or periodic limb movements of sleep (10%). Children with poor seizure control demonstrated significantly lower sleep efficiency, a higher arousal index, and a higher percentage of rapid-eye-movement sleep compared with children who were seizure-free or exhibited good seizure control. Patients with epilepsy and obstructive sleep apnea had significantly a higher body mass index, longer sleep latency, a higher arousal index, and a lower apnea-hypopnea index, but significantly more severe desaturation compared with patients with uncomplicated obstructive sleep apnea. A significant proportion of children with epilepsy referred for polysomnography with diverse sleep problems manifest sleep-disordered breathing, including obstructive sleep apnea syndrome.

Intravenous levetiracetam in children with epilepsy.

Intravenous levetiracetam recently became available for use in patients aged >16 years. There are few data about its safety and efficacy in children. We retrospectively analyzed data from children treated with intravenous levetiracetam. Ten patients (6 female, 4 male), aged 3 weeks to 19 years, were treated with intravenous levetiracetam at a mean dose of 50.5 mg/kg/day for a mean duration of 4.9 days. Four patients received intravenous levetiracetam for acute repetitive seizures/status epilepticus, and three as replacement for oral levetiracetam because administration of oral levetiracetam was temporarily infeasible. One patient each received intravenous levetiracetam for seizure prophylaxis during brain biopsy, as maintenance treatment after acute seizures, and as substitute for sodium valproate. Three of four patients with acute repetitive seizures/status epilepticus became seizure-free; the fourth patient had a partial reduction in seizure frequency. All three patients who received intravenous levetiracetam as substitute for oral levetiracetam tolerated the switch well. The other three patients were seizure-free on intravenous levetiracetam. No serious adverse effects were observed, and all patients completed treatment with intravenous levetiracetam for the intended period. Intravenous levetiracetam may be effective in various clinical situations requiring intravenous administration of an antiepileptic drug.

Stroke After Minor Head Trauma in Infants and Young Children With Basal Ganglia Calcification: A Lenticulostriate Vasculopathy?

The authors retrospectively reviewed charts of the children with basal ganglia stroke who either had preceding minor head injury or showed basal ganglia calcification on computed tomography (CT) scan. Twenty children, 14 boys and 6 girls were identified. Eighteen were aged between 7 months to 17 months. Presentation was with hemiparesis in 17 and seizures in 3. Preceding minor head trauma was noted in 18. Family history was positive in 1 case. Bilateral basal ganglia calcification on CT scan was noted in 18. Brain magnetic resonance imaging done in 18 infants showed acute or chronic infarcts in basal ganglia. Results of other laboratory and radiological investigations were normal. Four infants were lost to follow-up, 9 achieved complete or nearly completely recovery, and 7 had persistent neurological deficits. Basal ganglia calcification likely represents mineralized lenticulostriate arteries, a marker of lenticulostriate vasculopathy. Abnormal lenticulostriate vessels are vulnerable to injury and thrombosis after minor head trauma resulting in stroke.

Recurrent nocturnal tongue biting in a child with hereditary chin trembling.

A 13-month-old boy presented with repeated episodes of tongue biting during sleep. On evaluation, he was found to have hereditary chin trembling, a rare autosomal dominant condition characterized by continuous or intermittent tremulous activity of the mentalis muscle. This is the first report of this kind from India. The tongue biting appeared to be the result of parasomnia. Treatment with clonazepam was very effective; it completely ameliorated the symptom of tongue biting but had no effect on chin trembling.