The efficacy and side effects of topiramate on refractory epilepsy in infants and young children: a multi-center clinical trial.

OBJECTIVES: This study has been conducted to assess the efficacy and safety of topiramate in refractory epilepsies in infants and young children. METHODS: A prospective clinical trial was performed in three tertiary care hospitals, on 47 children aged 6-60 months with refractory epilepsy. Topiramate was added to at least two baseline anti-epileptic drugs. The efficacy was rated according to seizure type, frequency and duration. RESULTS: Children with refractory epilepsy were classified according to their clinical, neuro-imaging, and neurophysiological profile into infantile spasms (IS) (9 cases, 19%), Lennox-Gastaut syndrome (LGS) (25 cases, 53%) and other epilepsies (13 cases, 28%). Children were also classified into cryptogenic and symptomatic epilepsy. Topiramate was introduced as add-on therapy in a daily dose of 1 mg/kg/day for 2 weeks, followed by increments of 1-3 mg/kg/day at 2-week intervals, up to a maximum of 10 mg/kg/day. After a minimum treatment period of 6 months, 28 (60%) of the children had a satisfactory response (completely seizure free, or more than a 50% seizure reduction). The remaining 19 children (40%) had an unsatisfactory response (50% or less reduction in seizure frequency, no change or increased seizure frequency). Topiramate appeared to be equally effective in infantile spasms, Lennox-Gastaut syndrome and children with other types of epilepsy, with no significant difference between those with a satisfactory and an unsatisfactory response (p=0.089). There was also no significant difference in response between patients with cryptogenic and symptomatic epilepsy (p=0.360). Mild to moderate adverse effects, mainly somnolence, anorexia and nervousness, were present in 25 (53%) of children. One of the children developed hypothyroidism. CONCLUSION: Although the long term safety and possible adverse effects of topiramate have not been fully established in infants and young children, this study has shown that it is a useful option for children with frequent seizures unresponsive to standard anti-epileptic drugs.

The effect of Vigabatrin, Lamotrigine and Gabapentin on the fertility, weights, sex hormones and biochemical profiles of male rats.

PURPOSE: A case control study was conducted to assess the effect of Sabril (Vigabatrin), Lamictal (Lamotrigine) and Neurontin (Gabapentin) on fertility in male rats. Their effect on the body and organs weight and certain biochemical profiles including total serum protein, cholesterol, triglycerides, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum testosterone, and FSH levels were also measured. METHODS: several parameters, concerning fertility were measured in 40 albino male rats of Sprague Dawley strain, they were divided into 4 groups, group one received vehicle (distilled water), group two received Vigabatrin in a dose of 200 mg/kg body weight, group three received Lamotrigine in a dose of 30 mg/kg body weight, and group four received Gabapentin 100 mg/kg body weight. All the male rats in these groups received the different medications for a complete reproductive cycle (60 days). After 24 hours of the last dose, the animals were weighed and autopsied under light ether anesthesia. Parameter of fertility that has been measured in this study includes: sperm count and motility, weight of different reproductive organs, germ cell and interstitial cell population, serum testosterone and FSH levels and assessment of pregnancies in females mixed with tested males. Biochemical profiles such as serum cholesterol, serum triglycerides, serum bilirubin, SGOT, SGPT level are all measured. The results of the histological, histometerical studies and biochemical profiles were compared to that of the control group, and the significance of these results was measured using student's "t" test. RESULTS: There was significant reduction in the body weight and the weight of the testes, epididymis, seminal vesicles, ventral prostate, and vas deferens in the antiepileptic fed male rats in comparison to the control group (p > 0.001). There was significant reduction in testicular cells population dynamics including both germinal cell types and interstitial cell types in the antiepileptic fed male rats in comparison to the control group. There was also significant reduction in histometrical parameters and sperm dynamics in the antiepileptic fed male rats histologies in comparison to the control group. There was significant reduction in both testosterone and FSH levels (p < 0.001) in the antiepileptics fed male rats in comparison to the control group. There was also significant reduction in pregnancy rate observed in female rats exposed to the tested male rats among antiepileptic fed male rats compared to controls. The results of biochemical profiles assessment showed significant reduction in serum glucose, serum cholesterol, serum triglycerides levels and significant increase in serum bilirubin, SGOT, and SGPT levels in antiepileptics fed male rats in comparison to the control group. CONCLUSIONS: Fertility rate and other parameters concerned with fertility, sex hormones and certain biochemical profiles were significantly disturbed in male rats fed with three of the second-generation antiepileptic drugs Vigabatrin, Lamotrigine, and Gabapentin, indicating a possible toxic effect of these three medications on sexual organs, liver, and lipid metabolism.

Risk of seizure recurrence after a first unprovoked seizure: a prospective study among Jordanian children.

PURPOSE: There is wide variation in the reported recurrence rate after a first unprovoked seizure in children. We investigated the risk of recurrence after a first unprovoked seizure in Jordanian children and the risk factors associated with increased recurrence rate. METHODS: All consecutive patients aged 3 months-14 years who presented with their first unprovoked seizures between January 1997 and 2000, were included in a prospective study and followed up for 3 years for possible recurrence. Of the patients studied, there was slight male predominance (56.6%) and 55% of them were 2-9 years of age. Generalised seizures were reported in 75% and the remaining 25% had partial seizures. The duration of seizure was 1-4 minutes in 59%. Family history of epilepsy was positive in 31% and parental consanguinity in 32%. The role of these factors in increasing the risk of recurrence was also investigated. RESULTS: Two hundred sixty-five patients were included in the study and continued follow up for 3 years. Ninety-eight (37%) of them experienced seizure recurrence. Among the predictor factors for recurrence, partial seizure (P = 0.003) and positive family history (P = 0.000) were associated with a statistically significant increased risk. Sex, age, duration of seizure and consanguinity were not associated with increased risk of recurrence. CONCLUSION: Thirty-seven percent of the children studied experienced a second attack after a first unprovoked seizure over the 3 years follows up period. The risk of recurrence was significantly higher in children with a partial seizure (55%) and among those with a positive family history of epilepsy (59%). Age at first seizure, sex, duration of seizure and consanguinity were not significantly related to the risk of recurrence.

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.

Myoclonic seizure following intravenous verapamil injection: case report and review of the literature.

An 18-month-old girl with supraventricular tachycardia was given a dose of intravenous verapamil and suffered a short myoclonic seizure which occurred again when she was given second and third doses. In the absence of any predisposing factors, direct drug reaction was implicated as the cause of the seizure.

Demographic characteristics and risk factors of first febrile seizures: a Jordanian experience.

A prospective study of 203 children admitted with a first febrile seizure was carried out over 18 months. Aseptic meningitis was diagnosed in nine children (4%). The mean age of the children was 19.9 months and the peak age incidence (88%) was between 6 months and 3 years. Complex seizures were seen in 16 cases (8%). There was a history of perinatal asphyxia in 16 patients (8%), positive family history of epilepsy in 3%, of first degree relatives and a history of febrile seizures in siblings in 13%. Upper respiratory tract infection was the commonest triggering factor, diagnosed in 53% of cases. The third child was the most commonly affected (22%) in the family. There was a lower incidence of both complex febrile seizures and history of seizures in siblings compared to other studies. Lumbar puncture should be considered for all children below the age of 2 years, presenting with a first febrile seizure.

A clinical study of a large inbred kindred with pure familial spastic paraplegia.

BACKGROUND AND OBJECTIVES: Spastic paraplegia, an uncommon neurodegenerative disorder with phenotypic and genotypic heterogeneity, is mainly characterized by progressive weakness and spasticity of the lower limbs. We here present a large inbred family with pure familial spastic paraplegia outlining the clinical picture, the age at onset and the possible mode of inheritance. METHODS: This family was ascertained through two probands after which we structured an extended 10 generation pedigree. We examined 43 available family members to identify affected individuals based on fixed criteria. The clinical presentation and phenotypic specifics of this disease were studied in the affected members. We analyzed the possible mode of inheritance and the age at onset in this family. RESULTS: This 10 generation family reported about 50 affected individuals distributed over 5 consecutive generations. We identified 13 affected individuals out of the examined 43 and five individuals were classified as probably affected. We noticed the clinical specifics of this disorder in this family and identified some unique features not described in previous reports. DISCUSSION AND CONCLUSION: The mode of inheritance is either autosomal recessive or autosomal dominant with incomplete penetrance or variable expression of the age at onset. The age at onset seems to decrease with successive generations, either due to a true anticipatory phenomenon or to increased awareness. The unique features of this disorder in this family are discussed.

Lack of effectiveness of dexamethasone in neonatal bacterial meningitis.

UNLABELLED: 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.

Indications and benefits of computed tomography in childhood bacterial meningitis.

Over a 5 year period, 58 children with acute bacterial meningitis underwent computed tomography (CT) of the head. The major stated indications were partial, complex, or prolonged seizures in children younger than 5 years (60 per cent) and prolonged fever in the case of those older than 5 years (60 per cent). Abnormal findings on CT scan were seen in 27 (47 per cent); the remaining 31 (53 per cent) patients had normal or only non-specific dilatation of spaces containing cerebrospinal fluid (CSF) or basilar enhancement. The commonest CT abnormalities were seen in those patients who presented with complex seizure disorders. The commonest abnormal findings were subdural collection (33 per cent) followed by hydrocephalus (7 per cent). Subdural collection was seen mainly in patients with Haemophilus influenzae bacterial meningitis (90 per cent) while hydrocephalus was mainly seen in tuberculous meningitis. Positive findings of obvious therapeutic clinical relevance were present in only six cases (10 per cent). From the study we concluded that head CT provides an accurate means of diagnosing intracranial complications of bacterial meningitis, but it must be used conservatively as it has limited therapeutic applications in children with complicated bacterial meningitis. Computed tomography is indicated mainly in children with persistent neurologic dysfunction like complex seizure disorder, and is of little value in children with prolonged fever alone.

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.

Neonatal meningitis in northern Jordan.

A two-and-a-half year prospective study of neonatal meningitis in the two main referral hospitals in Northern Jordan was carried out to determine the clinical spectrum and particular characteristics of meningitis in the newborn. The 53 cases studied represented an incidence of 1.1 per 1000 live births. The commonest bacterial pathogen isolated was Klebsiella species (40 per cent) followed by Enterobacter (19 per cent). The mortality rate and neurological sequelae among surviving children were 32 and 39 per cent, respectively, with higher rates among preterm/low birth weight and early onset meningitis groups. Of the presenting clinical features, there was a highly positive association between two risk factors and outcome. A bulging anterior fontanelle was the only significant predictor of mortality (P = 0.009) and altered sensorium was the only predictive of post-meningitis sequelae (P = 0.016). The need to recognize that Klebsiella species is an increasingly important pathogen; cefotaxime or ceftazidime plus ampicillin are the most appropriate antibiotics to be used initially, and continuous surveillance thereafter have been stressed.

Familial pyoderma gangrenosum presenting in infancy.

UNLABELLED: Pyoderma gangrenosum (PG) is a rare, poorly understood skin disease that occurs in all age groups. Less than 0.4% of patients are infants and represent a diagnostic challenge as early lesions may resemble other skin disorders. Here we report for the first time three siblings affected with PG all presenting during infancy. Unlike the older age group, the ulcers spared the legs but involved the buttocks, thighs and perianal area in all the infants. CONCLUSION: This is the first reported family with PG affecting three siblings suggesting autosomal recessive inheritance. The diagnosis may be more difficult in infants due to absence of underlying associated disorders and the tendency of the lesions to appear in areas where infants frequently have other dermatoses. PG characteristically involves the buttocks, thighs and perianal area and spares the legs.

Prevalence of asthma and wheeze in primary school children in northern Jordan.

In order to determine the prevalence of asthma and wheeze in Northern Jordan, a questionnaire was distributed to 3540 school children aged 6-12 years in Irbid City. The completed questionnaires were returned by 3182 children, a response rate of 90%. The prevalence of physician-diagnosed asthma was 4.1%. Wheezing was reported by 8.3% of children. The male:female ratio was 2:1 for both conditions. In order of frequency, the triggering factors were respiratory tract infections, cold environment, exercise and dust. Statistically significant associations between wheezing (including asthma) and a family history of asthma, recurrent chest infections, eczema, allergic rhinicis and parental smoking were detected. Mode of delivery, breastfeeding and the presence of pets at home were not significantly associated. The prevalence of childhood asthma in Northern Jordan is similar to that in some countries of the developed world. Underdiagnosis may explain the relatively low prevalence of asthma found in this study population.

Sickle cell anaemia in Jordan and its clinical patterns.

Homozygous sickle cell anaemia (SCA) is an inherited red blood cell disorder in which haemoglobin A is replaced by haemoglobin S. The disease exhibits a wide spectrum of clinical behaviour which has been well described in neighbouring countries. In Jordan, however, the disease has never been characterized. We used reviews of patients' notes and clinic interviews at Princess Badi'a Teaching Hospital, Irbid, Jordan to describe the clinical presentation of the disease in our area. The total number of patients was 41 (28 boys and 13 girls) and the median age was 9 years (range 1.5-21). The median age at presentation was 2.5 years (range 0.5-11). The commonest presenting feature was pallor (62%). An unusual feature of the disease in this series is the presence of a palpable spleen in 44% of patients older than 8 years. Associated G6PD deficiency was present in 29% of boys. Different clinical patterns of SCA were observed. Haemoglobin F is unlikely to be an explanation for this variability since it has not been shown to correlate with a number of severity indices of the disease such as the frequency of blood transfusions, hospitalizations and painful crises. Although the disease haplotype is not known in Jordan, our geographical location between Asia and Africa may suggest the presence of more than one haplotype and consequently different clinical patterns.

Henoch-Schonlein purpura: clinical experience and contemplations on a streptococcal association.

Henoch-Schonlein Purpura (HSP) is a common cause of vasculitis in children. The role of an antecedent streptococcal infection is still controversial. The aim of this study is to verify such a relationship, as well as to provide a profile of the clinical features and the magnitude of this disorder in Jordan. We identified 69 cases of HSP below the age of 13 years between January 1991 and April 1994 admitted to the two main hospitals in northern Jordan. Thirty-five of these cases were prospectively enrolled during the last year of the study. Forty-three controls, frequency-matched to the cases on age and sex, were selected from the out-patient clinics of the same two hospitals. The minimum estimate of the annual incidence was 8.5/100,000. All patients recovered completely and were well after a mean period of follow-up of 16 months. The clinical features were essentially similar to those reported by others. Unusually, two of our cases followed mumps and one occurred after otitis media caused by Streptococcus pneumoniae. Forty-nine per cent of all patients in this series had evidence of a recent streptococcal infection (elevated antistreptolysin O titre) compared to 16 per cent of the controls. The difference was statistically significant (P = 0.004). This finding supports a role for antecedent streptococcal infection in the pathogenesis of HSP.