Autism services in low-resource areas.

OBJECTIVES: To explore access to intervention services for children with autism spectrum disorder (ASD) in Jordan. METHODS: We used prospective cross sectional design and survey methodology to collect information from the parents of a convenient sample of children with ASD aged 2.5-17 years and who attended pediatric neurology clinics in 3 different university affiliated hospitals in 3 geographic areas in Jordan from February to December 2018. RESULTS: We interviewed parents of 274 children with ASD. One hundred ninety-six (71.5%) received rehabilitation services. The average age at first session was 3.9 years. The most common services received were behavioral therapy (182; 66.4%). The average weekly hours were highest for speech and behavioral therapy; 6.25 and 6.64 respectively. Private centers for developmental disabilities were the most commonly used followed by private centers for ASD. The most common barriers were costs (138; 58%) and transportation (88; 37.5%). Most parents (198; 72.3%) prefer to receive rehabilitation in a specialized center for autism, and most did not want to receive training to train their child themselves. CONCLUSION: Most children with ASD in Jordan have limited access to recommended autism services. The development of future interventions must consider the needs of those living in limited resource regions.

Aseptic Meningitis and Its Viral Etiologies, Clinical Characteristics and Management Practices in Children: A Retrospective Hospital-Based Study From Jordan.

Purpose In this study, we aimed to describe the clinical characteristics, laboratory findings, aetiologies, and role of PCR in the decision on the management plan and duration of hospital stay in Jordanian children diagnosed with aseptic meningitis. Methods This retrospective observational cohort study included children diagnosed with meningitis who were admitted to the paediatric ward at Jordan University Hospital (JUH) during the period from January 2016 to August 2020. Patients were identified through the ICD9 discharge code of meningitis. Patients diagnosed with aseptic meningitis (defined as a patient with signs and symptoms of meningitis with a cerebrospinal fluid (CSF) white cell count of >5 cells/mm3, and a negative CSF Gram stain) were included, while patients who had low CSF glucose (<50% of serum) positive cerebrospinal fluid Gram stain and/or culture for bacterial meningitis were excluded. Files were reviewed to collect data on the clinical picture, viruses identified by the CSF viral polymerase chain reaction (PCR) panel, duration of medication, and hospital stay in patients with identified virus versus those with negative viral PCR. Results One hundred and thirty-one patients were included: 87 males (66.4%) and 44 females (33.5%). Fever was the most common presenting symptom, followed by headache, vomiting, and excessive sleep in 48.0%, 42.7%, and 35.8% of the patients, respectively. Prior oral antibiotic use was reported in 48/125 (38.4%) patients. White blood cell count (WBC) ranged from 4.800 to 22.000. cells/mL, 45 patients (34.3%) had counts above 15.000 cells/mL. C-reactive protein level was high in 61/103 (59.2%) patients. CSF WBC count was <100 in 62 (47.3%) patients while neutrophils predominance of >70% was present in 27 (20.6%) patients. Viral panel PCR was done for 100/131 (76.3%) patients and was positive in 66/100 (66%) patients; with enterovirus being the most common identified viruses (60/100; 60%). The average duration of hospital stay was 5.9 and 5.5 days for those with negative and positive PCR respectively. Ten (7.6%) patients had seizures upon presentation. None of the patients had any neurological sequel related to his meningitis. Conclusion Enteroviruses are the most common identified cause of paediatric aseptic meningitis in Jordan. Although PCR revealed an identified virus in around half of the patients, nevertheless, there was no adjustment in the management plan regarding duration of empirical antibiotic use and hospital stay. Increasing knowledge and awareness among clinicians on viral meningitis' lab characteristics might have great impact on duration of hospital stay and thus would be reflected on the patient and the healthcare system as well.

Facemask wearing does not impact neuro-electrical brain activity.

Given the massive use of facemasks (FMs) during the covid-19 pandemic, concerns have been raised regarding the effect of FMs wearing on overall health. This study aimed at evaluating the effect of surgical FM on brain neuro-electrical activity. Electroencephalography (EEG) background frequency (BGF) and background amplitude (BGA) was performed on 30 volunteers before (baseline), during and after wearing a FM for 60 min. Measurements were done during normal ventilation, hyperventilation and post-hyperventilation (PHVR). Blood gas levels were assessed at baseline and after FM use. EEG analysis concerning baseline (without FM) (BGA), was 47.69 ± 18.60 µV, wearing FM, BGA was 48.45 ± 17.79 µV, post FM use BGA was 48.08 ± 18.30 µV. There were no statistically significant differences between baseline BGA and BGA under FM and post FM. BGF, Baseline data were 10.27 ± 0.79, FM use 10.30 ± 0.76 and post FM use was 10.33 ± 0.76. There were no statistically significant differences between baseline BGF and BGF under FM and post FM. Venous blood gases, and peripheral oxygen saturation were not significantly affected by FM use. Short-term use of FM in young healthy individuals has no significant alteration impact on brain's neuro-electrical activity.

Genetic evaluation of children with autism spectrum disorders in developing and low-resource areas.

LAY ABSTRACT: Autism is the most common neurodevelopmental disorder in children worldwide. Genetic factors play an important role in the risk of developing autism. Determining the genetic cause of autism is key to understanding the biological processes that lead to the clinical manifestations of autism, and can inform the management and even prevention of this condition. Establishing genetic causes of autism requires collection of genetic data on a global scale. Limited research on genetic testing for individuals with autism is available from developing countries in low-resource regions. In this study, we explored the types of investigations ordered for Jordanian children with autism by their physicians. A representative sample of parents of children with autism in Jordan was questioned about the studies that their children received. We found that the recommended genetic testing was only performed in a small number of children with autism. In contrast, most children in the sample received non-genetic testing, which is not routinely recommended. We also explored the sociocultural factors that may influence the decision to perform genetic testing in this population. We discuss our findings in light of the data available from other developing and developed countries.

Population Pharmacokinetics Modeling of Lamotrigine in Jordanian Epileptic Patients Using Dried Blood Spot Sampling.

AIMS: To characterize the population pharmacokinetics of lamotrigine in Jordanian epileptic patients and to identify factors affecting therapeutic parameters. PATIENTS AND METHODS: A population pharmacokinetics model for lamotrigine was established based on a prospectively collected data of 52 steady-state concentrations from 38 adult and pediatric patients with epilepsy. Lamotrigine concentrations were determined by a dried blood spot liquid chromatography method. Data were analyzed according to a one-compartment model with first-order absorption and elimination using the nonlinear mixed effect modeling program. The covariates effect of total body weight, gender, age, and co-medication with topiramate, carbamazepine, phenytoin, phenobarbital, and valproic acid on lamotrigine clearance were investigated using a stepwise forward addition followed by a stepwise backward elimination. RESULTS: The final population pharmacokinetics model for lamotrigine clearance was as follows: CL/Fpop=θ1*exp (θ3*age)*exp (θ5*carbamazepine)*exp (θ6*valproic acid) , where θ1 is the relative clearance (L/hr) estimated, and θ3, θ5, and θ6 are the fixed parameters relating to age and co-medication with carbamazepine and valproic acid, respectively.The population mean value of lamotrigine total clearance generated in the final model (with covariates) was 2.12 L/hr. Inter-individual variability and residual unexplained variability expressed as the coefficient of variation was 37.1 and 26.1%, respectively. CONCLUSION: Lamotrigine total clearance in the Jordanian patients is comparable to that reported by others for Caucasian patients. Age and concomitant therapy with carbamazepine and valproic acid significantly affected lamotrigine clearance, and accounted for 48% of its inter-individual variability.

Could vagus nerve stimulation influence bone remodeling?

OBJECTIVES: To investigate the effect of vagus nerve stimulation (VNS) on the bone mineral density (BMD) in epileptic patients. METHODS: A prospective cohort study was conducted on individuals with refractory seizures who underwent VNS surgery between January 2012 and December 2018. BMD was measured preoperatively and between 6 months and one year after surgery. RESULTS: Twenty-one patients (mean age (±SD)=23.6±12.3 years) were recruited for the implantation of a VNS device. The mean absolute increase in lumbar BMD in the 21 patients was 0.04±0.04 g/cm2 resulting in an overall percent increase from baseline of 4.7±6.1%. BMD increased by an amount ≥ the least significant change (LSC) for the lumbar spine in 13 patients (61.9%). The lumbar Z score also increased in these patients from -1.22±1.15 to -0.88±1.22, P=0.006). Pre and Post VNA femoral BMD was measured in only 11 patients and, of those 3 showed a significant increase in BMD, 1 a significant decrease and 7 no change. CONCLUSION: The implantation of a VNS was associated with an increase in lumbar BMD. This study could lead to a new application for VNS in the treatment of osteoporosis.

Frequency of antiepileptic drugs and response change in pediatric patients receiving 2 or more antiepileptic drugs.

OBJECTIVE: To investigate the frequency of changes in antiepileptic drugs (AEDs) use, as well as concomitant changes in the degree of seizure control in pediatric patients, who are receiving 2 or more AEDs. METHODS: A prospective follow-up study at Jordan University Hospital`s pediatric neurology clinics was conducted on epileptic pediatric patients receiving at least 2 AEDs between December 2013 and April 2014. Patients were followed for 12 months. RESULTS: A total of 82 patients were included, with a mean age of 7.2+/- 4.7 years. The mean number of AEDs received by patients at enrollment was 2.4+/-0.6, and 2.5+/-0.7 after follow-up. Most patients (63.4%) experienced no change in seizure control, and the majority reported at least one adverse drug reaction. Most patients received lower doses than recommended, both at the beginning and end of the study. During the year, only 3 patients (4%) were eligible for dose tapering, which would then be converted to monotherapy. Follow-up appointments average was 4.2+/-2.9 visits/patients in one year. The frequency of medication changes and dose adjustment was very low, about one-third (29.3%) of patients requiring no change in AEDs during any follow-up visits. CONCLUSION: During the one year follow-up study, most patients on polytherapy maintained their level of response to the AEDs, with minimal changes in their regimen despite frequent follow-up visits. Only a small percent could be converted to AEDs monotherapy.

Parental use of conventional and complementary therapy for autism in Jordan.

OBJECTIVE: We investigated parental use of conventional therapies and complementary and alternative medicine (CAM) for children with autism in Jordan. METHOD: This prospective cross-sectional study was conducted from February 2018 through December 2018 at the paediatric neurology clinics of three tertiary referral hospitals in Jordan. The accompanying parent was interviewed to complete a structured questionnaire. RESULTS: 274 parents were interviewed. The most common medications used were those to treat hyperactivity (150; 54.7 %), anticonvulsants (60; 21.9 %), and sleep aids (6; 2.1 %). CAM was used by 129 parents (47.0 %). A casein-free diet was the most commonly used dietary modification (24; 8.7 %), while fish oil (Omega-3) was the most common supplement used (96; 35.0 %). Hyperbaric oxygen, chelation therapy, and antifungal treatment were also occasionally used. Higher parental education levels and access to rehabilitation services correlated with higher CAM use (p < 0.05).

Distal hereditary motor neuronopathy of the Jerash type is caused by a novel SIGMAR1 c.500A>T missense mutation.

BACKGROUND: Distal hereditary motor neuronopathies (dHMN) are a group of genetic disorders characterised by motor neuron degeneration leading to muscle weakness that are caused by mutations in various genes. HMNJ is a distinct form of the disease that has been identified in patients from the Jerash region of Jordan. Our aim was to identify and characterise the genetic cause of HMNJ. METHODS: We used whole exome and Sanger sequencing to identify a novel genetic variant associated with the disease and then carried out immunoblot, immunofluorescence and apoptosis assays to extract functional data and clarify the effect of this novel SIGMAR1 mutation. Physical and neurological examinations were performed on selected patients and unaffected individuals in order to re-evaluate clinical status of patients 20 years after the initial description of HMNJ as well as to evaluate new and previously undescribed patients with HMNJ. RESULTS: A homozygous missense mutation (c.500A>T, N167I) in exon 4 of the SIGMAR1 gene was identified, cosegregating with HMNJ in the 27 patients from 7 previously described consanguineous families and 3 newly ascertained patients. The mutant SIGMAR1 exhibits reduced expression, altered subcellular distribution and elevates cell death when expressed. CONCLUSION: In conclusion, the homozygous SIGMAR1 c.500A>T mutation causes dHMN of the Jerash type, possibly due to a significant drop of protein levels. This finding is in agreement with other SIGMAR1 mutations that have been associated with autosomal recessive dHMN with pyramidal signs; thus, our findings further support that SIGMAR1 be added to the dHMN genes diagnostic panel.

Parental knowledge and attitudes towards epilepsy -A study from Jordan.

PURPOSE: To explore the knowledge, attitudes and behaviors of parents whose children were diagnosed with epilepsy. METHODS: Cross-sectional questionnaire based study of parents who accompanied their children with epilepsy to the child neurology clinics at three university hospitals in Jordan. RESULTS: Most parents (427, 90.3%) knew that epilepsy is not related to a psychiatric disease. Approximately half of the parents (245, 51.8%) used the internet as their source of knowledge, and most used Arabic websites. Searching the word epilepsy was rarely used (51, 10.8%). Most of the parents (428,90.5%) were not restricting their children from watching TV or from using the computer (358,75.5%).However, many parents (280,59.2%) were restricting them from participating in sports. Parents had negative attitudes towards epilepsy; 189 (40.0%)thought that epileptic children can have normal intelligence, and 292 (61.7%) thought that they can continue into higher education. Greater parental knowledge of epilepsy was found to be correlated with the parental education level (p<0.05).Positive attitudes and behaviors towards epilepsy were found to be correlated with a higher parental education level, control of epilepsy,an absence of associated co morbidities, a higher income and internet use (p<0.05). CONCLUSION: This study sheds an important light on the current knowledge status and attitudes of parents of children with epilepsy, and is an invaluable tool for tailoring the delivery of information and support resources for families in our region.

Type and etiology of pediatric epilepsy in Jordan. A multi-center study.

OBJECTIVE: To study types and etiologies of epilepsy in Jordanian pediatric epileptic patients maintained on antiepileptic drugs using customized classification scheme of International League Against Epilepsy (ILAE) (2010) report. METHODS: This is a cross-sectional, multi-centre study on pediatric epileptic patients on antiepileptic drugs, who were managed in the pediatric neurology clinics at 6 teaching public hospitals in Jordan. RESULTS: Out of the 663 patients included in the study, (90.2%) had one seizure type, (53%) of this type were focal seizures followed by generalized seizures (41.5%) and spasms (5.5%). Distinctive constellations were found in 11/663 (1.7%) patients. Benign epilepsies with centrotemporal spikes were the most common electro clinical syndromes 60/221 (27.1%). Epilepsies attributed to structural-metabolic causes were documented in 278/663 (41.9%) patients, unknown causes 268/663(40.4%) and genetic causes in 117/663(17.7%). Most common causes of structural-metabolic group were due to perinatal insults (32%) and most common causes of the genetic group were the presumed genetic electro clinical syndromes (93.1%). CONCLUSION: Our study is on pediatric epilepsy, using customized classification scheme from the ILAE 2010 report which showed interesting results about type and etiology of epileptic seizures from developing country with potential impact on the international level.

Patterns of antiepileptic drugs use in epileptic pediatric patients in Jordan.

OBJECTIVE: To determine prescribing patterns of antiepileptic drugs (AEDs) in pediatric patients with confirmed diagnosis of epilepsy, and to provide knowledge of general practice of physicians. METHODS: The study was a multi-center crosssectional observational study, in specialized clinics for management of epilepsy in north, central and south Jordan. This study was conducted from January 2014 to July 2014. These were 3 from university tertiary care hospitals and 4 from governmental tertiary care hospitals. RESULTS: A total of 694 pediatric patients were included. Monotherapy AED use had the highest frequency 465 (67.0%), followed by dual therapy 162 (23.3%). The frequency of monotherapy in university hospitals was lower than governmental hospitals (p<0.05); however, Polytherapy was more frequent in younger children. Two old AEDs were most frequently prescribed as a monotherapy; Valproic acid 235 (50.5%) and carbamazepine 155 (33.3%). The most common combination in dual therapy was valproic acid with carbamazepine 28 (17.3%). The second most common combinations were carbamazepine with levetiracetam 21 (13.0%) or valproic acid with levetiracetam 20 (12.3%). CONCLUSION: Older AED remain first line drugs for use in both monotherapy and combination therapy for epileptic disorders. Polytherapy is associated with younger kids and being treated in a university hospital.

Donohue syndrome: a new case with a new complication.

Donohue syndrome (DS) is a very rare autosomal recessive disease affecting less than one in a million live births. It represents the most severe form of insulin resistance due to mutations involving the insulin receptor gene. DS is characterized by pre- and postnatal growth retardation with failure to thrive, lipoatrophy, muscle wasting, acanthosis nigricans, hypertrichosis, and dysmorphic features. Glucose homeostasis is affected with hyperinsulinemia, fasting hypoglycemia, and postprandial hyperglycemia. We report a Jordanian patient with genetically proven DS who had the classical physical features, progressive hypertrophic cardiomyopathy, cholestasis, and hyperglycemia, followed by hypoglycemia. In addition, the patient developed polyuria and uremia despite normal creatinine levels, hypernatremia, and hypertension. To our knowledge, these metabolic derangements were not previously reported in patients with DS.

Exome sequencing and functional validation in zebrafish identify GTDC2 mutations as a cause of Walker-Warburg syndrome.

Whole-exome sequencing (WES), which analyzes the coding sequence of most annotated genes in the human genome, is an ideal approach to studying fully penetrant autosomal-recessive diseases, and it has been very powerful in identifying disease-causing mutations even when enrollment of affected individuals is limited by reduced survival. In this study, we combined WES with homozygosity analysis of consanguineous pedigrees, which are informative even when a single affected individual is available, to identify genetic mutations responsible for Walker-Warburg syndrome (WWS), a genetically heterogeneous autosomal-recessive disorder that severely affects the development of the brain, eyes, and muscle. Mutations in seven genes are known to cause WWS and explain 50%-60% of cases, but multiple additional genes are expected to be mutated because unexplained cases show suggestive linkage to diverse loci. Using WES in consanguineous WWS-affected families, we found multiple deleterious mutations in GTDC2 (also known as AGO61). GTDC2's predicted role as an uncharacterized glycosyltransferase is consistent with the function of other genes that are known to be mutated in WWS and that are involved in the glycosylation of the transmembrane receptor dystroglycan. Therefore, to explore the role of GTDC2 loss of function during development, we used morpholino-mediated knockdown of its zebrafish ortholog, gtdc2. We found that gtdc2 knockdown in zebrafish replicates all WWS features (hydrocephalus, ocular defects, and muscular dystrophy), strongly suggesting that GTDC2 mutations cause WWS.

Anesthesia and electrocorticography for epilepsy surgery: a Jordanian experience.

OBJECTIVE: Electrocorticography (ECoG) may be used to guide epilepsy surgery. However, anesthetics can suppress epileptiform activity or induce confounding burst-suppression patterns and the relationship between ECoG results and seizure outcome is controversial. In this study, we evaluated the ECoG activity under several different anesthetics and examined the relationship between ECoG and outcome. METHODS: We retrospectively studied 44 patients who had ECoG during epilepsy surgery. Anesthesia was with fentanyl and isoflurane (n = 19), fentanyl and sevoflurane (n = 9), remifentanil and sevoflurane (n = 5), remifentanil and propofol (n = 9), and fentanyl with propofol sedation during local anesthesia (n = 2). Pre-resection ECoG was considered satisfactory if epileptiform activity was present and there was no burst-suppression. Post-resection ECoG was graded according to residual epileptiform activity: A (none), B (mild), C (moderate). Seizure outcome was graded: I (seizure free without medication), II (seizure free with medication), III (> 50% seizure reduction) or IV (< 50% seizure reduction). Grades I-III were considered beneficial. RESULTS: ECoG was satisfactory in 43 of the 44 surgeries, but one of the 11 recordings during propofol showed no epileptiform activity. Thirty-six of 37 patients (97%) with ECoG grade A or B and five of seven patients (71%) with ECoG grade C benefited from epilepsy surgery. Chi-squared, p > 0.05. CONCLUSIONS: Satisfactory ECoG is possible using isoflurane or sevoflurane with nitrous oxide and fentanyl or remifentanil or using propofol and remifentanil. However, one of eleven ECoGs under propofol was negative for epileptiform activity. The amount of post-resection ECoG epileptiform activity does not significantly correlate with seizure outcome.

Etiologies, outcomes, and risk factors for epilepsy in infants: a case-control study.

OBJECTIVES: To determine the etiologies, outcomes, and risk factors for epilepsy in infants. PATIENTS AND METHODS: This retrospective study included all children who had their first afebrile seizure between 1 and 12 months of age, and who were followed in the Child Neurology Clinic at the Jordan University Hospital from January 2004 to January 2006. Medical records were reviewed to collect demographic data and the clinical data pertaining to epilepsy. An age-matched control group of healthy children in a 1:2 ratio was included to determine the risk factors for epilepsy. For statistical analysis, SPSS, Version 13, was used. RESULTS: Fifty-five patients were included in the study group and 111 were in the control group. Epilepsy was classified as follows: symptomatic in 24 (43.6%) children, probably symptomatic (cryptogenic) in 28 (50.9%) children, and idiopathic in 3 (5.5%) children. The etiologies of epilepsy in the symptomatic group included hypoxic-ischemic encephalopathy (n=11), cortical malformations (n=5), neurocutaneous syndromes (n=2), metabolic disorders (n=4), leukodystrophy (n=1), and craniosynostosis (n=1). Twenty-seven patients (49%) were seizure-free at their last follow-up visit for at least the last 6 months; only six patients (10.9%) continued to have normal development at the time of their last follow-up examination. The risk factors for epilepsy included parental consanguinity (P=0.0003), a family history of global developmental delay (P=0.0002), a family history of epilepsy (P=0.010), and a positive perinatal history (P=0.011). CONCLUSION: This study emphasized that afebrile convulsions in infancy are rarely benign. Furthermore, consanguinity was shown to be a major risk factor for epilepsy.

Familiarity, knowledge, and attitudes towards epilepsy among attendees of a family clinic in Amman, Jordan.

OBJECTIVE: To investigate the present familiarity, knowledge, and attitudes of Jordanians towards epilepsy. METHODS: This is a cross-sectional study that was conducted over a 6-month period, from April 2006 to October 2006 at the family clinic of Jordan University Hospital, Amman, Jordan. A face-to-face questionnaire interview was conducted with 600 non-epileptic adults who visited the clinic during the study period. RESULTS: The sample matched the overall Jordanian population for literacy rate, however, included a higher proportion of females, and consequently findings may be taken as being only moderately representative of the Jordanian population. Ninety-eight percent of the respondents had heard about epilepsy, 47.3% knew someone with epilepsy, and 39.7% had witnessed a seizure. The major source of knowledge was word of mouth; knowledge about causes and treatment were far below the results reported in western countries. In addition, negative attitudes were present with regard to marriage and employment of epileptic patients (86.8% objected to marriage and 50.8% objected to employment). Eighty-three percent of respondents admitted that their knowledge of epilepsy was not satisfactory and were willing to learn more about epilepsy. The television was believed to be the most efficient and preferred way to disseminate knowledge about epilepsy. CONCLUSION: Although this study does not represent the whole Jordanian population, however, it demonstrated lack of knowledge and emphasized the extent of negative as well as positive attitudes towards epilepsy in Jordan.

Landau-Kleffner syndrome.

Landau-Kleffner syndrome is one of several language disorders associated with epilepsy or epileptiform abnormalities on EEG. Ultimately, these patients understand little or nothing of what they hear. Two thirds have behavioral abnormalities and close to 75% have seizures. Brain computerized tomography and MRI are normal, EEG changes show characteristic epileptiform changes. Antiepileptic drugs can easily control seizures, but language recovery is more difficult. Autoimmune etiology is considered likely and long-term prognosis remains variable.