Can Doppler sonography be used to diagnose neonatal cerebral infarction caused by portal vein thrombosis

Neonatal cerebral infarction is a serious and disabling condition. It is extremely rare if it occurs in association with portal vein thrombosis. We are reporting 2 cases of neonatal cerebral infarction with this etiology. The unique mechanism of cerebral infarction will be discussed. We propose that in the absence of any identifiable cause for the cerebral infarction, portal vein thrombosis should be considered and a Doppler sonography for the portal system is worth carrying out to confirm the diagnosis.     

Diagnosis and management of cerebral folate deficiency: A form of folinic acid-responsive seizures

Folinic acid-responsive seizures (FARS) are a rare treatable cause of neonatal epilepsy. They have characteristic peaks on CSF monoamine metabolite analysis, and have mutations in the ALDH7A1 gene, characteristically found in pyridoxine-dependent epilepsy. There are case reports of patients presenting with seizures at a later age, and with folate deficiency due to different mechanisms with variable response to folinic acid supplementation. Here, we report 2 siblings who presented with global developmental delay and intractable seizures who responded clinically to folinic acid therapy. Their work-up included metabolic and genetic testing. The DNA sequencing was carried out for the ALDH7A1 gene, and the folate receptor 1 (FOLR1) gene. They had very low 5-methyltetrahydrofolate (5-MTHF) in CSF with no systemic folate deficiency and no characteristic peaks on neurotransmitter metabolite chromatogram. A novel mutation in the FOLR1 gene was found. The mutation in this gene is shown to affect CSF folate transport leading to cerebral folate deficiency. The response to treatment with folinic acid was dramatic with improvement in social interaction, mobility, and complete seizure control. We should consider the possibility of this treatable condition in appropriate clinical circumstances early, as diagnosis with favorable outcome depends on the specialized tests.Folinic acid-responsive seizures (FARS) are a well-recognized cause of vitamin-responsive neonatal epilepsy.1 Patients present with seizures, either myoclonic or clonic, apnea, and irritability within 5 days after birth. Neuroimaging shows brain atrophy and variable white matter abnormalities. Some patients respond to pyridoxine alone, or have an initial response to it, only to become resistant later on and responding to folinic acid. The response to treatment has been variable. Gallagher et al2 reported that all surviving patients were developmentally delayed and 5 of 10 reported cases were deceased. Subsequently, it was demonstrated that FARS and pyridoxine-dependent epilepsy (PDE) are allelic; indeed, the molecular genetic basis of the 2 conditions is identical in at least some cases. Cerebrospinal fluid 5-methyltetrahydrofolate (5-MTHF) analysis was carried out in one of 7 cases, and reported normal in Hyland & Arnold’s study.1 A few cases of cerebral folate deficiency (CFD) presenting with seizures onset beyond the neonatal period (7 months to 11 years of age) have recently been reported with severe developmental regression,3 and movement disturbances with chorea,4 dystonia, and difficult ambulation.3,4 Neuroimaging showed brain atrophy and variable white matter abnormalities.3,4 The CSF biogenic metabolite did not show characteristic peaks, CSF 5-MTHF levels were found low,4 and FOLR1 gene mutations were reported.3,4 Mutations in the FOLR1 gene are associated with severely reduced concentrations of CSF 5-MTHF indicating that its gene product, folate receptor alpha (FRα), plays a crucial role in this transport process. This FRα defect causes a cerebral folate transport deficiency (MIM 136430), a progressive neurological disorder of late infantile onset that is characterized by psychomotor regression, epilepsy, and disturbed brain myelination as well as a depletion of white matter choline and often inositol.3 All of the cases responded to folinic acid supplementation becoming seizure free, or with better seizure control, and disappearance of chorea, and dystonia with better ambulation.3,4 Our objective in presenting these cases is to highlight that FARS is not uncommon. Early diagnosis and management can lead to better outcome.     

LGI‐1 antibody encephalitis in a seven‐year‐old girl

LGI‐1 antibody encephalitis is a rare autoimmune limbic encephalitis which has been reported predominantly in adults. Seizures in LGI‐1 antibody encephalitis exhibit significant semiological variability. Faciobrachial dystonic seizures are characteristically seen in this condition and have so far been described only in adults. Other seizure types have also been reported. We describe the case of a seven‐year‐old girl with LGI‐1 limbic encephalitis who presented with acute new‐onset seizures, and rapidly deteriorated over the course of a few weeks with very frequent seizures and encephalopathy, becoming non‐verbal and non‐ambulatory. The electroclinical presentation of this child with LGI‐1 encephalitis makes this case unique and further highlights the importance of a high index of suspicion for diagnosis in young children. Early diagnosis can lead to prompt and appropriate treatment with immunotherapy, and potential harmful treatments such as pharmacological coma can be avoided. To the best of our knowledge, this is the youngest case ever reporter. [Published with video sequences]     

The role of ketogenic diet in controlling epileptic seizures

Objectives:To study the role of the ketogenic diet (KD) in controlling seizures in children with medically resistant epilepsy in Saudi Arabia.Methods:This retrospective study was conducted in the Pediatric Neurology Clinic at a tertiary care epilepsy center. Thirty-one patients with medically resistant epilepsy were enrolled from 2013 to 2018. The seizure reduction variables were evaluated at 6, 12, 18 and 24 months after enrollment.Results:Of the 31 patients, 14 (45.2%) were males and 17 (54.8%) were females. The most common types of seizures were myoclonic seizures and mixed seizures, both of which occurred in 9 (29%) of the participants. Of the participants, 15 (48.4%) had seizures one to 5 times per day. Six months after starting a KD, 2 (6.45%) of participants were seizure-free; 6 (19.35%) were seizure-free after 12 months of treatment.Conclusion:The present study highlighted the effectiveness of KD in medically resistant epilepsy children to local population. A larger cohort is warrant to confirm these findings.

Epilepsy is a common neurological disorder. It is characterized by seizures and affects approximately 65–70 million people worldwide.1 Children and the elderly are most commonly affected by seizures; the condition is rarer in adults.2 Epilepsy remains a challenging neurological disorder despite effective pharmacological therapies.3 More than 30% of epileptic patients do not achieve complete control of seizures with available anti-epileptic drugs (AEDs).1,4 Around 20-40% of patients with epilepsy have refractory epilepsy “failure of, adequate trials of 2 tolerated, appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve the sustained seizure freedom” and who are not candidates for surgery, non-pharmacological interventions should be considered for ketogenic diet (KD) treatment.5,6The KD has been proposed for first time in 1920s as a non-pharmacologic treatment to control refractory childhood epilepsy.1 The KD is a high-fat, low-protein, low-carbohydrate diet, with ketogenic ratio of 4:1 or 3:1 in grams which is the most commonly administered ratio.7,8 The KD increases the production of ketone bodies, which brain uses these ketone bodies as an energy source instead of glucose.2 Some hypotheses have been proposed regarding the KD’s anti-seizure effects, suggesting that changes in the nature and degree of energy metabolism in the brain, changes in neurotransmitter function, changes in synaptic transmission, and changes in neuronal cellular properties may explain the diet’s effectiveness.9 Higher ketone levels correlate with better seizure control.9 Ten to 15% of children with epilepsy become completely seizure free on a KD.3 Furthermore, the KD has a prolonged beneficial effect even after it is discontinued.9The International Ketogenic Diet Study Group strongly recommends that the KD be considered as a treatment for children with epilepsy who fail to respond to two or three anticonvulsant medications, regardless of age or gender.9 Our objective was to study the efficacy of the KD in children with medically resistant epilepsy in Saudi Arabia.     

The prevalence of seizures in children with developmental delay

Objectives:To study the prevalence of seizures in children with GDD and identify the characteristics of such patients; to examine the association of GDD with epilepsy and to determine the effect of certain risk factors on this association.Methods:A retrospective cross-sectional study conducted at the pediatric neurology and developmental assessment clinic at King Fahad specialist hospital (KFSH), Saudi Arabia. All data were collected by reviewing the electronic medical records of 200 pediatric patients who presented with global developmental delay from February 2016 to April 2018.Results:The sample includes 200 children (113 males, 87 females) aged zero to 12 years. The largest group of participants came from the Dammam region, representing 27.5% of the sample. The prevalence of epilepsy in GDD patients was 56%; the epilepsy and non-epilepsy groups differed significantly in age. The most common type of seizure was generalized onset motor, which were observed in 37.5% of the sample. Problems during labor occurred in 15% of the sample; consanguineous marriage occurred in 61.6% of the participants. Neither of these factors differed significantly in the epilepsy and non-epilepsy groups. Advanced paternal age did differ significantly in the two groups (p=0.003).Conclusion:The prevalence of epilepsy is high in children with GDD, and of the factors studied here, the most significant variables affecting this correlation are the type of seizure and advanced paternal age.

Global developmental delay (GDD) is a general term used when children under the age of five years’ experience significant delays in 2 or more developmental domains (daily living activities, motor skills, speech/language, cognitive abilities, and social/emotional skills). The precise prevalence of GDD is unknown, but it is estimated to be 1%-3%.¹ Several studies have proposed an association between GDD and epilepsy.^1-3 Seizures are common; 4-10% of children experience at least one episode of seizures. Abnormal excessive or synchronous neuronal activity in the brain cause seizure and result in transient signs and/or symptoms.⁴ According to the International League Against Epilepsy (ILAE) patient can be diagnosed with epilepsy if the probability of further seizures after first unprovoked seizure similar to the general recurrence risk of at least 60% after 2 unprovoked seizures, occurring over the next 10 years.⁵ About 30% of children with epilepsy have behavioral or cognitive impairments.⁶ Epilepsy has been associated with neurocognitive impairment in children, and it can adversely impact school performance and long-term psychosocial prospects.^7,8 The impact of epilepsy on GDD can be explained by the effect of seizures on developing brain structures and functions and on repeated brain volume reduction (especially white matter tissue, which is seen in patients with childhood-onset temporal lobe epilepsy). Brain reduction is also associated with poor cognitive skills.^9-11 However, cognitive impairments in general often go undiagnosed; therefore, children with epilepsy should be periodically screened for GDD to enable early intervention and to maximize these patients’ chances for academic, professional, and social success.^2,3,6,7,9Little research has been carried out aiming to address the etiological factors of GDD in children attending a tertiary care hospital. This study was the only one study was done in Saudi Arabia in 2019 that focused on the prevalence of epilepsy in pediatric patients with developmental delay in Saudi Arabia, as it found that 56% of Saudi children with GDD have epilepsy. The same study showed that multiple variables were found to be related to GDD including consanguineous marriage (57%), and low birth weight (22%). Causes identified includes neuroradiology abnormalities in 58% of GDD children, 45% had abnormal EEG, genetic defects in 40%, and lastly metabolic disorders in one quarter of the participants.¹The aim of the present study is to examine the prevalence of epilepsy in children who visited a development clinic and the demographic characteristics of these patients. It will also examine the effects of other factors such as type of seizures, problems during pregnancy or labor, and advanced maternal or paternal age.