Prevalence, associated factors and clinical features of congenital syphilis among newborns in Mbarara hospital, Uganda.

BACKGROUND: While congenital syphilis is a significant public health problem that can cause severe disabilities, little is known about the situation in Uganda. We describe prevalence, associated factors and clinical presentation of congenital syphilis in Mbarara, Uganda. METHODS: A cross sectional study was carried out among mother- newborn dyads from the postnatal ward of Mbarara Regional Referral Hospital (MRRH). After obtaining informed consent, a structured questionnaire was used to capture data on risk factors for congenital syphilis. A finger prick was performed on the mothers for Treponema Pallidum Haemagglutination Assay (TPHA). If TPHA was positive, a venous blood sample was collected from the mother to confirm active infection using Rapid Plasma Reagin (RPR). Venous blood was drawn from a newborn if the mother tested positive by TPHA and RPR. A newborn with RPR titres 4 times higher than the mother was considered to have congenital syphilis. We fit logistic regression models to determine factors associated with congenital syphilis. RESULTS: Between June and September 2015, we enrolled 2500 mothers and 2502 newborns. Prevalence of syphilis was 3.8% (95% CI 3.1-4.6) among newborn infants and 4.1% (95% CI 3.4-5.0) among their mothers. Maternal age <25 years, past history of genital ulcer, a past history of abnormal vaginal discharge, and not receiving treatment of at least one of genital ulcer, genital itching, lower abdominal pain and abnormal vaginal discharge in the current pregnancy were the risk factors associated with congenital syphilis. The most common clinical feature was hepatosplenomegaly. CONCLUSIONS: We found higher-than-expected syphilis sero-prevalence rates in a high risk population of postnatal mothers and their newborns in Uganda. Bridge populations for syphilis may include mothers not tested during pregnancy, who are usually married and not treated. In accordance with our results, the national policy for syphilis control in Uganda should be strengthened to include universal syphilis screening amongst mother-newborn pairs in postnatal clinics with subsequent partner notification.

Trends in the Incidence of Sudden Unexpected Infant Death in the Newborn: 1995-2014.

OBJECTIVE: To evaluate the epidemiology of sudden unexpected infant death (SUID) over a 20-year period in the US, to assess the potential frequency of sudden unexpected postnatal collapse in the early days of life, and to determine if SUID rates in the neonatal period (0-27 days) have changed in parallel with rates in the postneonatal periods, including the percentages attributed to codes that include accidental suffocation. STUDY DESIGN: Data from the US Centers for Disease Control and Prevention Linked Birth/Infant Death Records for 1995-2014 were analyzed for the first hour, day, week, and month of life. A comparison of neonatal and postneonatal data related to SUID, including accidental suffocation, was carried out. RESULTS: Death records for 1995-2014 indicate that, although SUID rates in the postneonatal period have declined subsequent to the 1992 American Academy of Pediatrics sleep position policy change, newborn SUIDs have failed to decrease, and the percentage of SUIDs attributed to unsafe sleep conditions has increased significantly in both periods; 29.2% of the neonatal cases occurred within the first 6 days of life. CONCLUSIONS: The frequency of SUIDs during the neonatal period warrants ongoing attention to all circumstances contributing to this category of deaths. The development of a standardized definition of sudden unexpected postnatal collapse and a national registry of these events is recommended. Ongoing research on the effects of early neonatal practices on postneonatal SUID should also be encouraged.

Urolithiasis on the ketogenic diet with concurrent topiramate or zonisamide therapy.

Children with refractory epilepsy who are co-treated with the ketogenic diet (KD) and carbonic anhydrase inhibitor (CA-I) anti-epileptic medications including topiramate (TPM) and zonisamide (ZNS) are at risk for urolithiasis. Retrospective chart review of all children treated with ketogenic therapy at our institution was performed in order to estimate the minimal risk of developing signs or symptoms of stone disease. Children (N=93) were classified into groups according to KD+/-CA-I co-therapy. Fourteen patients had occult hematuria or worse, including 6 with radiologically confirmed stones. Three of 6 calculi developed in the KD+ZNS group of 17 patients who were co-treated for a cumulative total of 97 months (3.1 stones per 100 patient months). One confirmed stone was in the KD+TPM group of 22 children who were co-treated for a cumulative total of 263 months (0.4 stones per 100 patient months). All six patients had at least three of five biochemical risk factors including metabolic acidosis, concentrated urine, acid urine, hypercalciuria and hypocitraturia. Standard of care interventions to minimize hypercalciuria, crystalluria and stone formation used routinely by pediatric nephrologists should also be prescribed by neurologists treating patients with combination anti-epileptic therapy. Non-fasting KD initiation, fluid liberalization, potassium citrate prophylaxis as well as regular laboratory surveillance are indicated in this high risk population.

MRI findings reveal three different types of tubers in patients with tuberous sclerosis complex.

Cortical tubers are very common in tuberous sclerosis complex (TSC) and widely vary in size, appearance and location. The relationship between tuber features and clinical phenotype is unclear. The aim of the study is to propose a classification of tuber types along a spectrum of severity, using magnetic resonance imaging (MRI) characteristics in 35 patients with TSC and history of epilepsy, and to investigate the relationship between tuber types and genetics, as well as clinical manifestations. Three types of tubers were identified based on the MRI signal intensity of their subcortical white matter component. (1) Tubers Type A are isointense on volumetric T1 images and subtly hyperintense on T2 weighted and fluid-attenuated inversion recovery (FLAIR); (2) Type B are hypointense on volumetric T1 images and homogeneously hyperintense on T2 weighted and FLAIR; (3) Type C are hypointense on volumetric T1 images, hyperintense on T2 weighted, and heterogeneous on FLAIR characterized by a hypointense central region surrounded by a hyperintense rim. Based on the dominant tuber type present, three distinct patient groups were also identified: Patients with Type A tuber dominance have a milder phenotype. Patients with Type C tuber dominance have more MRI abnormalities such as subependymal giant cell tumors, and were more likely to have an autism spectrum disorder, a history of infantile spasms, and a higher frequency of epileptic seizures, compared to patients who have a dominance in Type B tubers, and especially to those with a Type A dominance.

Associations between electroencephalographic and magnetic resonance imaging findings in tuberous sclerosis complex.

Nearly 90% of patients with tuberous sclerosis complex (TSC) develop epilepsy; however the mechanisms of epileptogenesis remain unclear. Some cortical tubers are thought to be epileptogenic while others are not. This study aimed to evaluate whether tuber burden, size or type seen on magnetic resonance imaging (MRI) co-registers with interictal epileptiform discharges on electroencephalogram (EEG). EEG and MRI data from 69 patients with TSC were reviewed by dividing the cerebrum into four quadrants. Quadrants containing greatest tuber burden, largest tuber, calcified tubers, cyst-like tubers, and no tubers were identified on MRI. For EEG analysis, spikes and sharp waves were counted and averaged to a value per minute, and each quadrant was assigned a score. MRI and EEG findings were compared in each patient. The presence of a cyst-like tuber in a quadrant correlated with a higher incidence of epileptiform activity in the same quadrant (p=0.002). This finding supports the notion that cyst-like cortical tubers may contribute to the more severe epilepsy profile seen in TSC patients with these lesions. Quadrants containing greatest tuber burden, largest tubers, and calcified tubers were not predictive of regional interictal epileptiform activity. Furthermore, quadrants without any apparent tuber co-registered with interictal epileptiform discharges in two patients, suggesting a multifactorial component of epileptogenicity in TSC.

Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy.

PURPOSE: To report the efficacy, safety, and tolerability of the low glycemic index treatment (LGIT) in pediatric epilepsy. METHODS: A retrospective chart review was performed on patients initiating the LGIT at the Massachusetts General Hospital between January 2002 and June 2008. Demographic and clinical information including seizure type, baseline seizure frequency, medications, blood chemistries, side effects, and anthropometrics were collected. Initiation of the LGIT was done in an outpatient setting. Patients were educated by a dietitian to restrict foods with high glycemic index and to limit total daily carbohydrates to 40-60 g. Change in seizure frequency was assessed at 1-, 3-, 6-, 9-, and 12-month follow-up intervals. RESULTS: Seventy-six children were included in the study. Eighty-nine percent had intractable epilepsy (>or=3 antiepileptic drugs). A greater than 50% reduction from baseline seizure frequency was observed in 42%, 50%, 54%, 64%, and 66% of the population with follow-up available at 1, 3, 6, 9, and 12 months, respectively. Increased efficacy was correlated with lower serum glucose levels at some time points, but not with beta-hydroxybutyrate (BOHB) changes or ketosis status at any time point. Only three patients reported side effects (transient lethargy). Blood urea nitrogen (BUN) was elevated in approximately one-third of follow-up laboratory studies. No significant changes were seen in body mass index (BMI) or BMI z-score at any follow-up interval. The most cited reason for treatment discontinuation was the restrictiveness of the diet, in 18 patients (24%). CONCLUSION: The LGIT was associated with reduced seizure frequency in a large fraction of patients, with limited side effects.

Low glycemic index treatment: implementation and new insights into efficacy.

Despite the substantial efficacy of the ketogenic diet (KD) in treating refractory epilepsy, use of the KD remains limited because of difficulties in implementation and tolerability. An effective alternative dietary approach is a low glycemic index treatment (LGIT), which liberalizes the extreme carbohydrate restriction of the KD but restricts the type of carbohydrate-containing foods to those that produce relatively small changes in blood glucose. Foods with a "glycemic index" of less than 50 produce less than half the area-under-the-curve elevation of blood glucose compared to a reference food. The LGIT approach produces comparable efficacy to the classic KD, but tolerability is improved and implementation is much simpler. The LGIT appears to be a viable first-line dietary therapy for epilepsy.

Intrafamilial phenotypic variability in tuberous sclerosis complex.

Clinical manifestations were retrospectively assessed in 5 families with tuberous sclerosis complex, including 1 pair of monozygotic twins. Interfamilial variation in tuber count was significantly larger than intrafamilial variation. Severity of epilepsy and cognitive profiles varied both between and within families, particularly between the monozygotic twins, and IQ was inversely related to tuber count. Cutaneous, renal, and cardiac findings did not appear to cluster within families. Although the monozygotic twins displayed similar physical manifestations of tuberous sclerosis complex (renal and cardiac hamartomas), they differed markedly in neurocognitive profiles. Phenotypic variation within these families may be explained largely as a function of the randomness of second-hit events that cause hamartomas in tuberous sclerosis complex or by as-yet-unidentified genetic modifiers. Familial variation in tuberous sclerosis complex phenotype has important implications for genetic counseling.

Safety and tolerability of the ketogenic diet in pediatric epilepsy: effects of valproate combination therapy.

PURPOSE: To evaluate safety and tolerability of ketogenic diet (KGD) and valproate (VPA) cotherapy in the treatment of intractable seizures. METHODS: The patient records of children who underwent KGD initiation at the Massachusetts General Hospital for Children from February 2002 to September 2004 were retrospectively assessed. Efficacy was measured by comparing reported seizure frequency at baseline and at 3-month intervals thereafter. Adverse events and reasons for terminating the diet were tabulated. RESULTS: Of 71 patients who underwent KGD initiation, 24 were concomitantly using VPA at the time of initiation. The most serious adverse events were two cases of acute pancreatitis (2.8%), both of which occurred in patients not taking VPA. The most common complications in both groups were acidosis (39.4%), nausea and vomiting (23.9%), hypertriglyceridemia (21.1%), lethargy (18.3%), and behavioral changes and irritability (15.5%). No significant difference in adverse-event profiles was found between the VPA group and the non-VPA group. At 1 year, 32 patients remained on the diet, including 11 in the VPA group. Efficacy was nearly identical in these two groups. CONCLUSIONS: KGD and VPA combination therapy is relatively safe and effective in refractory pediatric epilepsy. Adverse-event profiles of patients on KGD and VPA cotherapy are similar to those of patients on the KGD without VPA. In considering possible treatment options for intractable seizures, cotherapy with these two modalities should not be excluded for safety or tolerability concerns. In some patients, this combination may provide optimal seizure control.