Azhar S. Daoud

A Homozygous Mutation in Human PRICKLE1 Causes an Autosomal-Recessive Progressive Myoclonus Epilepsy-Ataxia Syndrome

Progressive myoclonus epilepsy (PME) is a syndrome characterized by myoclonic seizures (lightning-like jerks), generalized convulsive seizures, and varying degrees of neurological decline, especially ataxia and dementia. Previously, we characterized three pedigrees of individuals with PME and ataxia, where either clinical features or linkage mapping excluded known PME loci. This report identifies a mutation in PRICKLE1 (also known as RILP for REST/NRSF interacting LIM domain protein) in all three of these pedigrees. The identified PRICKLE1 mutation blocks the PRICKLE1 and REST interaction in vitro and disrupts the normal function of PRICKLE1 in an in vivo zebrafish overexpression system. PRICKLE1 is expressed in brain regions implicated in epilepsy and ataxia in mice and humans, and, to our knowledge, is the first molecule in the noncanonical WNT signaling pathway to be directly implicated in human epilepsy.

Effectiveness of iron therapy on breath-holding spells

OBJECTIVE The objective of this study is to investigate the effect of iron therapy on breath-holding spells (BHS). METHODOLOGY Sixty-seven children with BHS were enrolled in a clinical trial to evaluate the effect of iron therapy on BHS. At the beginning of therapy, the clinical, laboratory, and demographic characteristics of the patients in the treatment group (n = 33) and placebo group (n = 34) were comparable. Patients were assessed weekly for the first 8 weeks and then every 2 weeks for the next 8 weeks. Response to therapy was assessed by the change in the frequency of BHS. RESULTS Children treated with iron showed significant reduction in the frequency of BHS (88%) compared with the frequency (6%) in the placebo group. As expected, the treated group showed a significant improvement of a number of blood indexes compared with the placebo group. Baseline mean levels of hemoglobin and total iron binding capacity were predictive of a favorable response to iron treatment. CONCLUSION Results of this study indicate that iron therapy is effective in the treatment of BHS and that iron-deficient children seem to be more likely to benefit from such therapy. Response to iron therapy was strongly correlated with improvement in blood indexes.

Iron status: A possible risk factor for the first febrile seizure

Summary:  Purpose: We conducted a controlled study to investigate the relation of iron status and first febrile seizure (FFS).

Public knowledge and attitudes towards epilepsy in Jordan.

BACKGROUND Social acceptances of people with epilepsy very often constitute a considerable problem for patients and their family. Nationwide opinion polls on the public knowledge and attitudes towards epilepsy have been reported from several countries. The purpose of this study is to assess the knowledge and attitudes of the Jordanian public towards epilepsy, which have not been verified before. METHODS A total of 16,044 people (8158 males and 7886 females) living in different areas of Jordan were interviewed by invitation using standard four set questionnaire constructed from previous similar studies (Caveness and Gallup) that tested public knowledge and attitudes toward epilepsy. Two hundred and thirty senior students of the faculty of pharmacy at Jordan University of Science and Technology are involved in this study. Each student interviewed at least 50 individuals, aged 18 years or older, from their immediate community including family members, relatives, neighbors and friends by invitation. The interviews took place during the period from February to June of 2005. RESULTS Eighty-eight percent had read or knew about epilepsy, and 52.4% had witnessed an epileptic attack at least once in their life. From the people interviewed, 84.7% believed that the cause of epilepsy is a neurological disease, and 80.6% believe that the main symptom is brief loss of consciousness. The response of the younger participants and those with higher education were statistically significant more positive regarding the knowledge on causes and symptoms of epilepsy. More than 70% accepts shaking hands with people with epilepsy; they also believe that people with epilepsy are able to have children and to get high academic degrees. Less than 50% accepts letting their children play with children with epilepsy or employ people with epilepsy. Nine percent had negative attitudes, and believed that patients with epilepsy are insane and 88.5% objects the marriage of people with epilepsy to their sons or daughters. Approximately one third of the respondents believed that epilepsy is more dangerous than diabetes mellitus and hypertension. CONCLUSIONS The overall knowledge and attitudes of Jordanians towards epilepsy is relatively comparable with the results from Asian countries but more negative when compared with reports from the Western countries. Consequently, well-organized educational campaigns are needed to improve public perception about epilepsy.

Lack of effectiveness of dexamethasone in neonatal bacterial meningitis.

Abstract A clinical trial was conducted to determine whether dexamethasone as adjunctive therapy alters the outcome of bacterial meningitis in neonates. Fifty-two full-term neonates with bacterial meningitis were enrolled in a prospective study. Infants were alternately assigned to receive either dexamethasone or not. Twenty-seven received dexamethasone in addition to standard antibiotic treatment and 25 received antibiotics alone. Dexamethasone therapy was started 10–15 min before the first dose of antibiotics in a dose of 0.15 mg/kg per 6 h for 4 days. Baseline characteristics, clinical and laboratory features in the two groups were virtually similar. Both groups showed a similar clinical response and similar frequency of mortality and sequelae. Six (22%) babies in the treatment group died compared to 7 (28%) in the control group (P = 0.87). At follow up examinations up to the age of 2 years, 6 (30%) of dexamethasone recipients and 7 (39%) of the control group had mild or moderate/severe neurological sequelae. Audiological sequelae were seen in two neonates in the dexamethasone group compared to one in the control group. Conclusion Adjunctive dexamethasone therapy does not improve the outcome of neonatal bacterial meningitis.

Effectiveness of sodium valproate in the treatment of Sydenham's chorea

We treated 15 children with Sydenhams chorea with sodium valproate at a dose of 15 to 20 mg/kg/d. In 13 of them the chorieform movements disappeared within 1 week of therapy. The remaining 2 had incomplete response. Two patients relapsed; 1 of them responded to the reintroduction of valproate. The mean duration of treatment was 6.7 weeks. We observed no major side effects. This study strongly suggests that valproate is an effective drug in the treatment of Sydenhams chorea.

Clinical sinusitis in children attending primary care centers

OBJECTIVES To determine the proportion of children who meet the clinical criteria for the diagnosis of sinusitis among all children attending primary care pediatric practices, to explore the relationship between passive smoking and the occurrence of sinusitis and to study the role of antibiotics in the management of sinusitis. DESIGN A prospective observational cohort study. SETTING Outpatient Pediatric Clinics of Jordan University of Science and Technology and Princess Rahma Teaching Hospital. Patients. All children ages 1 to 10 years presenting for any reason to participating practices. METHODS Physicians participating in this study completed a questionnaire on all children attending the primary care centers, detailing the presence of nasal congestion or discharge, the duration of symptoms, daytime cough and whether symptoms were improving. The presence or absence of smokers in the family was also recorded. Children meeting our clinical criteria for sinusitis were further evaluated for other signs and symptoms including the type of medication prescribed. The severity of symptoms was reassessed at 10-day follow-up after the first visit. RESULTS The study population was composed of 3001 children, of whom 249 met our clinical criteria for diagnosis of sinusitis (8.3%; 95% confidence interval, 7.3 to 9.3%). The prevalence rate of clinical sinusitis was greater among children age 5 years and older than among those younger (9.3% vs. 7.2%, P = 0.04). Children exposed to passive smoking in the household had clinical sinusitis significantly more than those not exposed (68.8% vs. 1.2%, P = 0.00). Antibiotics were prescribed for 80% of children who fulfilled the clinical criteria for diagnosis of sinusitis. Marked improvement of symptoms at the 10-day follow-up visit was reported among those who received antibiotics compared with those who did not (91% vs. 21.4%, P = 0.00). CONCLUSIONS Sinusitis is not an uncommon problem in children, passive smoking might be a contributing factor and a course of antibiotic therapy is beneficial.

Henoch-Schonlein purpura and streptococcal infection: A prospective case-control study

A prospective, matched, case-control study conducted over a period of 3 years was designed to examine the association of group A beta-haemolytic streptococcal infections and Henoch-Schonlein purpura. Demographic and clinical data were collected as well as measurement of antistreptolysin O titres and throat swab culture on all children admitted with Henoch-Schonlein purpura, as well as their matched controls. Antistreptolysin O titre positivity was associated with a 10-fold increase in the risk of Henoch-Schonlein purpura. Renal involvement was common among cases with positive antistreptolysin O titres (27%) compared with cases with a negative titre (8%) but this difference has no statistical significance.

The clinical spectrum of Henoch-Schönlein purpura in infants and young children

Henoch-Schönlein purpura is a common cause of childhood vasculitis. The rarity of the disease under 2 years of age has been the subject of few reports. We present the clinical spectrum of Henoch-Schönlein purpura in 12 children younger than 2 years of age at presentation. The median age at presentation was 11 months. The purpuric skin rash was present in all patients and involved the face in 10 of them. While oedema was a prominent feature in all of our patients only one third had involvement of the kidneys, gastro-intestinal tract or joints. All patients recovered completely after a mean duration of follow up of 10.6 months (range 2–39 months).ConclusionHenoch-Schönlein purpura under the age of 2 years is characterized clinically by oedema and a purpuric skin rash which frequently affects the face. Involvement of the joints, kidneys and gastro-intestinal tract is uncommon and the prognosis is excellent. The clinical spectrum in this age group is a continuation with that of Henoch-Schönlein purpura in older children suggesting a nosological entity.

Risk factors for childhood epilepsy: A case-control study from Irbid, Jordan

OBJECTIVE The goal of this case-control study is to identify the significance of certain risk factors for epilepsy in a population of epileptic children in Northern Jordan. The risk factors examined are febrile convulsions, head trauma, central nervous system infections, abnormal perinatal history, family history and parental consanguinity. METHODOLOGY We designed a case-control study for patients attending the outpatient neurology clinic of Princess Rahma Teaching Hospital in Irbid, Jordan during a 7-month period. Controls were selected, matched for age and sex, from a group of non-epileptic patients attending the general paediatrics outpatient clinic in the same hospital and during the same period. Data about the investigated risk factors were obtained by personal interview and review of the medical records and were analysed statistically for significance. RESULTS The total number of participants was 200 patients and controls each. History of febrile convulsions, head trauma, abnormal perinatal history and family history showed a statistically significant increase risk for developing epilepsy. Central nervous system infections and parental consanguinity did not add to the risk of developing epilepsy. CONCLUSION Positive family history for epilepsy, head trauma, febrile convulsions and abnormal perinatal history were shown to have a statistically significant association with epilepsy in patients attending Princess Rahma Teaching Hospital in Northern Jordan. Although consanguinity is widely practised in Jordan, it appears that it does not increase the risk of epilepsy probably due to the small contribution of monogenic recessive epilepsies to the population with epilepsy.