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Background The etiology of neonatal sepsis is often not identified. Molecular methods can identify pathogens that culture-based methods miss. Most cases of neonatal sepsis globally are treated empirically per WHO guidelines with intravenous ampicillin and gentamicin, which may not be the best regimen for all pathogens. Methods We prospectively enrolled 800 neonates presenting with signs of sepsis to two Ugandan hospitals. Blood and cerebrospinal fluid were subjected to 16S rRNA sequencing, which identified Paenibacillus thiaminolyticus in 33/800 (4%) neonates. We confirmed the presence of P. thiaminolyticus by quantitative polymerase chain reaction (PCR). We describe neonatal and birth characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacillosis. We performed antibiotic susceptibility testing and genomic analyses on three clinical isolates successfully grown in the laboratory. Results Neonates presented at a median age of 3 (1, 7) days. Fever (86%), irritability (78%) and seizures (52%) were common presenting signs (Figure). Most neonates were born vaginally (73%) at a medical facility (79%). Twelve (36%) had an adverse outcome: 5 (15%) neonates died; 4 (14%) survivors developed postinfectious hydrocephalus and three (9%) additional survivors had neurodevelopmental impairment. All three isolates were resistant to vancomycin, two were resistant to penicillin and ampicillin and one was unlikely to be sensitive to ceftriaxone; all were susceptible to gentamicin and meropenem. The genomes of all three strains contained multiple beta-lactamase genes and a cluster of genes that encodes a type IV pilus. Clinical signs at presentation for neonates with good and poor outcomes followng paenibacillosis Conclusion Molecular methods such as 16S rRNA sequencing and PCR can be used to improve the identification of pathogens causing neonatal sepsis. Paenibacillosis is an important emerging cause of neonatal sepsis in Uganda and is likely an underrecognized cause of postinfectious hydrocephalus in the region and possibly elsewhere. Antibiotics commonly used for neonatal sepsis may be inadequate for the treatment of paenibacillosis. Additional studies to understand the pathophysiology and optimal treatment of this novel infection are urgently needed to prevent neonatal mortality and morbidity including postinfectious hydrocephalus. Disclosures Jessica E. Ericson, MD, MPH, Abbvie: Advisor/Consultant Abhaya Kulkarni, MD, MSc, PhD, Medtronic: Advisor/Consultant.

Paenibacillus thiaminolyticusmay be an underdiagnosed cause of neonatal sepsis. We prospectively enrolled a cohort of 800 neonates presenting with a clinical diagnosis of sepsis at two Ugandan hospitals. Quantitative polymerase chain reaction specific toP. thiaminolyticusand to thePaenibacillusgenus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with virus detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacillosis vs. clinical sepsis. Median age at presentation was 3 (interquartile range 1, 7) days. Fever (92%), irritability (84%) and seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus and one (3%) additional survivor had neurodevelopmental impairment without hydrocephalus. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.

OBJECTIVE Hydrocephalus in infants, particularly that with a postinfectious etiology, is a major public health burden in Sub-Saharan Africa. The authors of this study aimed to determine whether surgical treatment of infant postinfectious hydrocephalus in Uganda results in sustained, long-term brain growth and improved cognitive outcome. METHODS The authors performed a trial at a single center in Mbale, Uganda, involving infants (age < 180 days old) with postinfectious hydrocephalus randomized to endoscopic third ventriculostomy plus choroid plexus cauterization (ETV+CPC; n = 51) or ventriculoperitoneal shunt (VPS; n = 49). After 2 years, they assessed developmental outcome with the Bayley Scales of Infant Development, Third Edition (BSID-III), and brain volume (raw and normalized for age and sex) with CT scans. RESULTS Eighty-nine infants were assessed for 2-year outcome. There were no significant differences between the two surgical treatment arms in terms of BSID-III cognitive score (p = 0.17) or brain volume (p = 0.36), so they were analyzed together. Raw brain volumes increased between baseline and 2 years (p < 0.001), but this increase occurred almost exclusively in the 1st year (p < 0.001). The fraction of patients with a normal brain volume increased from 15.2% at baseline to 50.0% at 1 year but then declined to 17.8% at 2 years. Substantial normalized brain volume loss was seen in 21.3% patients between baseline and year 2 and in 76.7% between years 1 and 2. The extent of brain growth in the 1st year was not associated with the extent of brain volume changes in the 2nd year. There were significant positive correlations between 2-year brain volume and all BSID-III scores and BSID-III changes from baseline. CONCLUSIONS In Sub-Saharan Africa, even after successful surgical treatment of infant postinfectious hydrocephalus, early posttreatment brain growth stagnates in the 2nd year. While the reasons for this finding are unclear, it further emphasizes the importance of primary infection prevention and mitigation strategies along with optimizing the child’s environment to maximize brain growth potential.

OBJECTIVE This study investigated the incidence of postoperative subdural collections in a cohort of African infants with postinfectious hydrocephalus. The authors sought to identify preoperative factors associated with increased risk of development of subdural collections and to characterize associations between subdural collections and postoperative outcomes. METHODS The study was a post hoc analysis of a randomized controlled trial at a single center in Mbale, Uganda, involving infants (age < 180 days) with postinfectious hydrocephalus randomized to receive either an endoscopic third ventriculostomy plus choroid plexus cauterization or a ventriculoperitoneal shunt. Patients underwent assessment with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III; sometimes referred to as BSID-III) and CT scans preoperatively and then at 6, 12, and 24 months postoperatively. Volumes of brain, CSF, and subdural fluid were calculated, and z-scores from the median were determined from normative curves for CSF accumulation and brain growth. Linear and logistic regression models were used to characterize the association between preoperative CSF volume and the postoperative presence and size of subdural collection 6 and 12 months after surgery. Linear regression and smoothing spline ANOVA were used to describe the relationship between subdural fluid volume and cognitive scores. Causal mediation analysis distinguished between the direct and indirect effects of the presence of a subdural collection on cognitive scores. RESULTS Subdural collections were more common in shunt-treated patients and those with larger preoperative CSF volumes. Subdural fluid volumes were linearly related to preoperative CSF volumes. In terms of outcomes, the Bayley-III cognitive score was linearly related to subdural fluid volume. The distribution of cognitive scores was significantly different for patients with and those without subdural collections from 11 to 24 months of age. The presence of a subdural collection was associated with lower cognitive scores and smaller brain volume 12 months after surgery. Causal mediation analysis demonstrated evidence supporting both a direct (76%) and indirect (24%) effect (through brain volume) of subdural collections on cognitive scores. CONCLUSIONS Larger preoperative CSF volume and shunt surgery were found to be risk factors for postoperative subdural collection. The size and presence of a subdural collection were negatively associated with cognitive outcomes and brain volume 12 months after surgery. These results have suggested that preoperative CSF volumes could be used for risk stratification for treatment decision-making and that future clinical trials of alternative shunt technologies to reduce overdrainage should be considered.

To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda.Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV.The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43-134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30-76.18; p = 0.003), maternal age25 years (aOR 4.54; 95% CI 1.40-19.29; p = 0.02), and increasing neonatal age (aOR 1.08 for each day older; 95% CI 1.00-1.16; p = 0.05), were associated risk factors for CMV in neonates with clinical sepsis. We found a 2-fold higher maternal vaginal shedding in eastern (45%) vs western (22%) Uganda during parturition (n = 22/49 vs 11/50, the Fisher exact test; p = 0.02). In infants with PIH, the prevalence in blood was 24% and in infants with NPIH, it was 20%. CMV was present in the cerebrospinal fluid (CSF) of 13% of infants with PIH compared with 0.5% of infants with NPIH (n = 26/205 vs 1/194, p0.0001).Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized.

BACKGROUND: There are currently no published data directly comparing postoperative seizure incidence following endoscopic third ventriculostomy (ETV), with/without choroid plexus cauterization (CPC), to that for ventriculoperitoneal shunt (VPS) placement. OBJECTIVE: To compare postoperative epilepsy incidence for ETV/CPC and VPS in Ugandan infants treated for postinfectious hydrocephalus (PIH). METHODS: We performed an exploratory post hoc analysis of a randomized trial comparing VPS and ETV/CPC in 100 infants (

ImportancePost-infectious hydrocephalus in infants is a major public health burden in sub-Saharan Africa.ObjectiveTo determine long-term brain growth and cognitive outcome after surgical treatment of infant post-infectious hydrocephalus in Uganda.DesignProspective follow-up of a previously randomized cohort.SettingSingle center in Mbale, Uganda.ParticipantsInfants (InterventionsEndoscopic or shunt surgery.Main outcomesBayley Scales of Infant Development (BSID-3) and brain volume on computed tomography (raw and normalized for age and sex) at 2 years after treatment.ResultsEighty-nine infants were assessed for 2-year outcome. There were no significant differences between the two surgical treatment arms, so they were analyzed together. Raw brain volumes increased between baseline and 24 months (median change=361 cc, IQR=293 to 443, pConclusions and RelevanceIn sub-Saharan Africa, even after successful surgical treatment of infant post-infectious hydrocephalus, post-treatment brain growth stagnates in the second year. While the reasons for this are unclear, this emphasizes the importance of primary infection prevention strategies along with optimizing the child’s environment to maximize brain growth potential.Trial RegistrationClinicalTrials.gov number, NCT01936272KEY POINTSQuestionWhat is the brain growth and cognitive trajectory of infants treated for post-infectious hydrocephalus in Uganda?FindingsIn this prospective follow-up of a cohort of 89 infants, early normalization of brain volume after treatment was followed by brain growth stagnation in the second year, with many falling back into the sub-normal range. Poor brain growth was associated with poor cognitive outcome.MeaningSuccessful surgical treatment of hydrocephalus is not sufficient to allow for adequate brain growth and cognitive development. Interventions aimed at primary infection prevention and reducing comorbidities are needed to improve brain growth potential.

Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium Paenibacillus, together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of Paenibacillus thiaminolyticus. This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference Paenibacillus strain. These findings show that an unbiased pan-microbial approach enabled characterization of Paenibacillus in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections.

Postinfectious hydrocephalus (PIH), often following neonatal sepsis, is the most common cause of pediatric hydrocephalus world-wide, yet the microbial pathogens remain uncharacterized. Characterization of the microbial agents causing PIH would lead to an emphasis shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention. We examined blood and CSF from 100 consecutive cases of PIH and control cases of non-postinfectious hydrocephalus (NPIH) in infants in Uganda. Genomic testing was undertaken for bacterial, fungal, and parasitic DNA, DNA and RNA sequencing for viral identification, and extensive bacterial culture recovery. We uncovered a major contribution to PIH from Paenibacillus, upon a background of frequent cytomegalovirus (CMV) infection. CMV was only found in CSF in PIH cases. A facultatively anaerobic isolate was recovered. Assembly of the genome revealed a strain of P. thiaminolyticus. In mice, this isolate designated strain Mbale, was lethal in contrast with the benign reference strain. These findings point to the value of an unbiased pan-microbial approach to characterize PIH in settings where the organisms remain unknown, and enables a pathway towards more optimal treatment and prevention of the proximate neonatal infections.One Sentence SummaryWe have discovered a novel strain of bacteria upon a frequent viral background underlying postinfectious hydrocephalus in Uganda.

IntroductionManaging paediatric hydrocephalus with shunt placement is especially risky in resource-limited settings due to risks of infection and delayed life-threatening shunt obstruction. This study evaluated a new evidence-based treatment algorithm to reduce shunt-dependence in this context.MethodsA prospective cohort design was used. The CURE Protocol employs preoperative and intraoperative data to choose between endoscopic treatment and shunt placement. Data were prospectively collected for 730 children in Uganda (managed by local neurosurgeons highly experienced in the protocol) and, for external validation, 96 children in Nigeria (managed by a local neurosurgeon trained in the protocol).ResultsThe age distribution was similar between Uganda and Nigeria, but there were more cases of postinfectious hydrocephalus in Uganda (64.2% vs 26.0%, pConclusionUse of the CURE Protocol in two centres with different populations and surgeon experience yielded similar 6-month results, with over half of all children remaining shunt-free. Where feasible, this could represent a better public health strategy in low-resource settings than primary shunt placement.

Postinfectious hydrocephalus in infants is a major health problem in sub-Saharan Africa. The conventional treatment is ventriculoperitoneal shunting, but surgeons are usually not immediately available to revise shunts when they fail. Endoscopic third ventriculostomy with choroid plexus cauterization (ETV-CPC) is an alternative treatment that is less subject to late failure but is also less likely than shunting to result in a reduction in ventricular size that might facilitate better brain growth and cognitive outcomes.We conducted a randomized trial to evaluate cognitive outcomes after ETV-CPC versus ventriculoperitoneal shunting in Ugandan infants with postinfectious hydrocephalus. The primary outcome was the Bayley Scales of Infant Development, Third Edition (BSID-3), cognitive scaled score 12 months after surgery (scores range from 1 to 19, with higher scores indicating better performance). The secondary outcomes were BSID-3 motor and language scores, treatment failure (defined as treatment-related death or the need for repeat surgery), and brain volume measured on computed tomography.A total of 100 infants were enrolled; 51 were randomly assigned to undergo ETV-CPC, and 49 were assigned to undergo ventriculoperitoneal shunting. The median BSID-3 cognitive scores at 12 months did not differ significantly between the treatment groups (a score of 4 for ETV-CPC and 2 for ventriculoperitoneal shunting; Hodges-Lehmann estimated difference, 0; 95% confidence interval [CI], -2 to 0; P=0.35). There was no significant difference between the ETV-CPC group and the ventriculoperitoneal-shunt group in BSID-3 motor or language scores, rates of treatment failure (35% and 24%, respectively; hazard ratio, 0.7; 95% CI, 0.3 to 1.5; P=0.24), or brain volume (z score, -2.4 and -2.1, respectively; estimated difference, 0.3; 95% CI, -0.3 to 1.0; P=0.12).This single-center study involving Ugandan infants with postinfectious hydrocephalus showed no significant difference between endoscopic ETV-CPC and ventriculoperitoneal shunting with regard to cognitive outcomes at 12 months. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01936272 .).

Neurosurgery in Uganda was virtually non-existent up until late 1960s. This changed when Dr. Jovan Kiryabwire spearheaded development of a neurosurgical unit at Mulago Hospital in Kampala. His work ethic and vision set the stage for rapid expansion of neurosurgical care in Uganda.At the beginning of the 2000s, Uganda was a country of nearly 30 million people, but had only 4 neurosurgeons. Neurosurgery's progress was plagued by challenges faced by many developing countries, such as difficulty retaining specialists, lack of modern hospital resources, and scarce training facilities. To combat these challenges 2 distinct programs were launched: 1 by Dr. Benjamin Warf in collaboration with CURE International, and the other by Dr. Michael Haglund from Duke University. Dr. Warf's program focused on establishing a facility for pediatric neurosurgery. Dr. Haglund's program to increase neurosurgical capacity was founded on a "4 T's Paradigm": Technology, Twinning, Training, and Top-Down. Embedded within this paradigm was the notion that Uganda needed to train its own people to become neurosurgeons, and thus Duke helped establish the country's first neurosurgery residency training program.Efforts from overseas, including the tireless work of Dr. Benjamin Warf, have saved thousands of children's lives. The influx of the Duke Program caused a dynamic shift at Mulago Hospital with dramatic effects, as evidenced by the substantial increase in neurosurgical capacity. The future looks bright for neurosurgery in Uganda and it all traces back to a rural village where 1 man had a vision to help the people of his country.

Background: Managing paediatric hydrocephalus with shunt placement is especially risky in resource-limited settings due to risks of infection and delayed life-threatening shunt obstruction. This study evaluated a new evidence-based treatment algorithm to reduce shunt-dependence in this context. Methods: The CURE Protocol employs pre- and intra-operative data to choose between endoscopic treatment and shunt placement. Data were prospectively collected for 730 children in Uganda (managed by local neurosurgeons highly-experienced in the protocol) and, for external validation, 96 children in Nigeria (managed by a local neurosurgeon trained in the protocol). Findings: The age distribution was similar between Uganda and Nigeria, but there were more cases of post-infectious hydrocephalus in Uganda (64·2% vs 26·0%, p

OBJECTIVEClinical and economic repercussions of ventricular shunt infections are magnified in low-resource countries. The efficacy of antibiotic-impregnated shunts in this setting is unclear. A previous retrospective cohort study comparing the Bactiseal Universal Shunt (BUS) and the Chhabra shunt provided clinical equipoise; thus, the authors conducted this larger randomized controlled trial in Ugandan children requiring shunt placement for hydrocephalus to determine whether there was, in fact, any advantage of one shunt over the other.METHODSBetween April 2013 and September 2016, the authors randomly assigned children younger than 16 years of age without evidence of ventriculitis to either BUS or Chhabra shunt implantation in this single-blind randomized controlled trial. The primary outcome was shunt infection, and secondary outcomes included reoperation and death. The minimum follow-up was 6 months. Time to outcome was assessed using the Kaplan-Meier method. The significance of differences was tested using Wilcoxon rank-sum, chi-square, Fisher’s exact, and t-tests.RESULTSOf the 248 patients randomized, the BUS was implanted in 124 and the Chhabra shunt in 124. There were no differences between the groups in terms of age, sex, or hydrocephalus etiology. Within 6 months of follow-up, there were 14 infections (5.6%): 6 BUS (4.8%) and 8 Chhabra (6.5%; p = 0.58). There were 14 deaths (5.6%; 5 BUS [4.0%] vs 9 Chhabra [7.3%], p = 0.27) and 30 reoperations (12.1%; 15 BUS vs 15 Chhabra, p = 1.00). There were no significant differences in the time to primary or secondary outcomes at 6 months’ follow-up (p = 0.29 and 0.17, respectively, Wilcoxon rank-sum test).CONCLUSIONSAmong Ugandan infants, BUS implantation did not result in a lower incidence of shunt infection or other complications. Any recommendation for a more costly standard of care in low-resource countries must have contextually relevant, evidence-based support.Clinical trial registration no.: PACTR201804003240177 (http://www.pactr.org/)

Effective treatment of children with medulloblastoma requires a functioning multi-disciplinary team with adequate neurosurgical, neuroradiological, pathological, radiotherapy and chemotherapy facilities and personnel. In addition the treating centre should have the capacity to effectively screen and manage any tumour and treatment-associated complications. These requirements have made it difficult for many low and middle-income countries (LMIC) centres to offer curative treatment. This article provides management recommendations for children with standard-risk medulloblastoma (localised tumours in children over the age of 3-5 years) according to the level of facilities available.

Object It is not known whether previous endoscopic third ventriculostomy (ETV) affects the risk of shunt failure. Different epochs of hydrocephalus treatment at the CURE Children's Hospital of Uganda (CCHU)—initially placing CSF shunts in all patients, then attempting ETV in all patients, and finally attempting ETV combined with choroid plexus cauterization (CPC) in all patients—provided the opportunity to assess whether prior endoscopic surgery affected shunt survival. Methods With appropriate institutional approvals, the authors reviewed the CCHU clinical database to identify 2329 patients treated for hydrocephalus from December 2000 to May 2007. Initial ventriculoperitoneal (VP) shunt placement was performed in 900 patients under one of three circumstances: 1) primary nonselective VP shunt placement with no endoscopy (255 patients); 2) VP shunt placement at the time of abandoned ETV attempt (with or without CPC) (370 patients); 3) VP shunt placement subsequent to a completed but failed ETV (with or without CPC) (275 patients). We analyzed time to shunt failure using the Kaplan-Meier method to construct survival curves, Cox proportional hazards regression modeling, and risk-adjusted analyses to account for possible confounding differences among these groups. Results Shunt failure occurred in 299 patients, and the mean duration of follow-up for the remaining 601 was 28.7 months (median 18.8, interquartile range 4.1–46.3). There was no significant difference in operative mortality (p = 0.07 by log-rank and p = 0.14 by Cox regression adjusted for age and hydrocephalus etiology) or shunt infection (p = 0.94, log-rank) among the 3 groups. There was no difference in shunt survival between patients treated with primary shunt placement and those who underwent shunt placement at the time of an abandoned ETV attempt (adjusted hazard ratio [HR] 1.14, 95% CI 0.86–1.51, p = 0.35). Those who underwent shunt placement after a completed but failed ETV (with or without CPC) had a lower risk of shunt failure (p = 0.008, log-rank), with a hazard ratio (adjusted for age at shunting and etiology) of 0.72 (95% CI 0.53–0.98), p = 0.03, compared with those who underwent primary shunt placement without endoscopy; but this was observed only in patients with postinfectious hydrocephalus (PIH) (adjusted HR 0.55, 95% CI 0.36–0.85, p = 0.007), and no effect was apparent for hydrocephalus of noninfectious etiologies (adjusted HR 0.98, 95% CI 0.64–1.50, p = 0.92). Improved shunt survival after failed ETV in the PIH group may be an artifact of selection arising from the inherent heterogeneity of ventricular damage within that group, or a consequence of the timing of shunt placement. The anticipated benefit of CPC in preventing future ventricular catheter obstruction was not observed. Conclusions A paradigm for infant hydrocephalus involving intention to treat by ETV with or without CPC had no adverse effect on mortality or on subsequent shunt survival or infection risk. This study failed to demonstrate a positive effect of prior ETV or CPC on shunt survival.

Object The authors have previously reported on the overall improved efficacy of endoscopic third ventriculostomy (ETV) combined with choroid plexus cauterization (CPC) for infants younger than 1 year of age. In the present study they specifically examined the long-term efficacy of ETV with or without CPC in 35 infants with congenital aqueduct stenosis treated at CURE Children's Hospital of Uganda during the years 2001–2006. Methods Infants with congenital aqueductal stenosis were treated during 2 distinct treatment epochs: all underwent ETV alone, and subsequently all underwent ETV-CPC. Prospectively collected data in the clinical database were reviewed for all infants with an age < 1 year who had been treated for hydrocephalus due to congenital aqueductal stenosis. Study exclusion criteria included: 1) a history or findings on imaging or at the time of ventriculoscopy that suggested a possible infectious cause of the hydrocephalus, including scarred choroid plexus; 2) an open aqueduct or an aqueduct obstructed by a membrane or cyst rather than by stenosis; 3) severe malformations of the cerebral hemispheres including hydranencephaly, significant segments of undeveloped brain, or schizencephaly; 4) myelomeningocele, encephalocele, Dandy-Walker complex, or tumor; or 5) previous shunt insertion. The time to treatment failure was analyzed using the Kaplan-Meier method to construct survival curves. Log-rank (Mantel-Cox) and Gehan-Breslow-Wilcoxon tests were used to determine whether differences between the 2 treatment groups were significant. Results Thirty-five patients met the study criteria. Endoscopic third ventriculostomy alone was performed in 12 patients (mean age 4.7 months), and combined ETV-CPC was performed in 23 patients (mean age 3.5 months). For patients without treatment failure, the mean and median follow-ups were, respectively, 51.6 and 48.0 months in the ETV group and 31.2 and 26.4 months in the ETV-CPC group. Treatment was successful in 48.6% of the patients who underwent ETV alone, as accurately predicted by the Endoscopic Third Ventriculostomy Success Score (ETVSS), and in 81.9% of the patients who underwent ETV-CPC (p = 0.0119, log-rank test; p = 0.0041, Gehan-Breslow-Wilcoxon test; HR 6.42 [95% CI 1.51–27.36]). Conclusions Combined ETV-CPC is significantly superior to ETV alone for infants younger than 1 year of age with congenital aqueductal stenosis. The fact that the outcome for ETV alone was accurately predicted by the ETVSS suggests that these results are applicable in developed countries.

Object Dandy-Walker complex (DWC) is a continuum of congenital anomalies comprising Dandy-Walker malformation (DWM), Dandy-Walker variant (DWV), Blake pouch cyst, and mega cisterna magna (MCM). Hydrocephalus is variably associated with each of these, and DWC-associated hydrocephalus has mostly been treated by shunting, often with 2-compartment shunting. There are few reports of management by endoscopic third ventriculostomy (ETV). This study is the largest series of DWC or DWM-associated hydrocephalus treated by ETV, and the first report of treatment by combined ETV and choroid plexus cauterization (ETV/CPC) in young infants with this association. Methods A retrospective review of the CURE Children's Hospital of Uganda clinical database between 2004 and 2010 identified 45 patients with DWC confirmed by CT scanning (25 with DWM, 17 with DWV, and 3 with MCM) who were treated for hydrocephalus by ETV/CPC. Three were excluded because of other potential causes of hydrocephalus (2 postinfectious and 1 posthemorrhagic). Results The median age at treatment was 5 months (88% of patients were younger than 12 months). There was a 2.4:1 male predominance among patients with DWV. An ETV/CPC (ETV only in one) was successful with no further operations in 74% (mean and median follow-up 24.2 and 20 months, respectively [range 6–65 months]). The rate of success was 74% for DWM, 73% for DWV, and 100% for MCM; 95% had an open aqueduct, and none required posterior fossa shunting. Conclusions Endoscopic treatment of DWC-associated hydrocephalus should be strongly considered as the primary management in place of the historical standard of creating shunt dependence.

Object This study characterizes the first clinical series of encephalocele (EC) from East or Central Africa, and is the largest reported from the African continent. The authors explored survival, the efficacy of primary endoscopic management of associated hydrocephalus, and ethnic differences in EC location. Methods One hundred ten consecutive children presented to CURE Children's Hospital of Uganda for treatment of EC over a 9-year period. Clinical data, including patient demographic information, birth date, lesion type (sincipital, parietal, or occipital), operative data, and subsequent course had been entered prospectively into a clinical database. Home visits to update the status of those lost to follow-up were done when possible. With appropriate institutional approvals, the database was reviewed for this retrospective study. Two-tailed probability values calculated using the Fisher exact test were used to assess the significance of differences among groups, with p < 0.05 being considered significant. The Kaplan-Meier method was used for analysis of survival and treatment success probabilities. Results There were 53 (48%) occipital, 33 (30%) sincipital, and 24 (22%) parietal lesions. Occipital lesions were significantly more common among children of Bantu origin (p = 0.02). Nilotes demonstrated a roughly equal distribution among sincipital, parietal, and occipital locations. The female/male ratio was 1.2, with no difference between EC types (range 1.0–1.4, p = 0.6–0.8). Of 110 patients, 108 (98%) underwent surgical repair at a median age of 1 month (mean 15.7 months), whereas 2 had treatment for hydrocephalus only. Wound revision was required in 13% of cases. Surgery-related mortality was 3%. One-year and 5-year survival rates were 87% (95% CI 0.79–0.93) and 61% (95% CI 0.51–0.70), respectively. Hydrocephalus required treatment in 32%, and was equally common among the 3 EC types. Thirteen patients were treated with combined endoscopic third ventriculostomy/choroid plexus cauterization (ETV/CPC) and 2 with ETV alone, whereas 18 patients received primary shunt placement. Predicted treatment success at 1 year was 79% for ETV or ETV/CPC (95% CI 0.50–0.94) and 47% for shunt placement (95% CI 0.24–0.71). Conclusions Analysis of this first EC series from this region suggests that sincipital lesions are 3 times more common in East than in West Africa. Occipital lesions predominate in patients of Bantu origin, but not among those of Nilotic descent. Hydrocephalus incidence was equally common among different EC types, and endoscopic treatment was more successful (79%) than shunting (47%) at 1 year. The 5-year mortality rate was similar to that for infants with myelomeningocele in Uganda, and more than twice that for their unaffected peers.

Object Infantile hydrocephalus in East Africa is predominantly postinfectious. The microbial origins remain elusive, since most patients present with postinfectious hydrocephalus after antecedent neonatal sepsis (NS) has resolved. Methods To characterize this syndrome in Ugandan infants, the authors used polymerase chain reaction targeting bacterial 16S ribosomal DNA from CSF to determine if bacterial residua from recent infections were detectable. Bacteria were identified based on the relationship of genetic sequences obtained with reference bacteria in public databases. The authors evaluated samples from patients presenting during dry and rainy seasons and performed environmental sampling in the villages of patients. Results Bacterial DNA was recovered from 94% of patients. Gram-negative bacteria in the phylum Proteobacteria were the most commonly detected. Within this phylum, Gammaproteobacteria dominated in patients presenting after infections during the rainy season, and Betaproteobacteria was most common following infections during the dry season. Acinetobacter species were identified in the majority of patients admitted after rainy season infection. Conclusions Postinfectious hydrocephalus in Ugandan infants appears associated with predominantly enteric gram-negative bacteria. These findings highlight the need for linking these cases with antecedent NS to develop more effective treatment and prevention strategies.

Object In Uganda, childhood hydrocephalus is common and difficult to treat. In some children, endoscopic third ventriculostomy (ETV) can be successful and avoid dependence on a shunt. This can be especially beneficial in Uganda, because of the high risk of infection and long-term failure associated with shunting. Therefore, the authors developed and validated a model to predict the chances of ETV success, taking into account the unique characteristics of a large sub-Saharan African population. Methods All children presenting with hydrocephalus at CURE Children's Hospital of Uganda (CCHU) between 2001 and 2007 were offered ETV as first-line treatment and were prospectively followed up. A multivariable logistic regression model was built using ETV success at 6 months as the outcome. The model was derived on 70% of the sample (training set) and validated on the remaining 30% (validation set). Results Endoscopic third ventriculostomy was attempted in 1406 patients. Of these, 427 were lost to follow-up prior to 6 months. In the remaining 979 patients, the ETV was aborted in 281 due to poor anatomy/visibility and in 310 the ETV failed during the first 6 months. Therefore, a total of 388 of 979 (39.6% and [55.6% of completed ETVs]) procedures were successful at 6 months. The mean age at ETV was 12.6 months, and 57.8% of cases were postinfectious in origin. The authors' logistic regression model contained the following significant variables: patient age at ETV, cause of hydrocephalus, and whether choroid plexus cauterization was performed. In the training set (676 patients) and validation set (303 patients), the model was able to accurately predict the probability of successful ETV (Hosmer-Lemeshow p value > 0.60 and C statistic > 0.70). The authors developed the simplified CCHU ETV Success Score that can be used in the field to predict the probability of ETV success. Conclusions The authors' model will allow clinicians to accurately identify children with a good chance of successful outcome with ETV, taking into account the unique characteristics and circumstances of the Ugandan population.

OBJECT The incidence of temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (MTS) can be high in developing countries. Current diagnosis of MTS relies on structural MRI, which is generally unavailable in developing world settings. Given widespread effects on temporal lobe structure beyond hippocampal atrophy in TLE, the authors propose that CT volumetric analysis can be used in patient selection to help predict outcomes following resection. METHODS Ten pediatric patients received preoperative CT scans and temporal resections at the CURE Children's Hospital of Uganda. Engel classification of seizure control was determined 12 months postoperatively. Temporal lobe volumes were measured from CT and from normative MR images using the Cavalieri method. Whole brain and fluid volumes were measured using particle filter segmentation. Linear discrimination analysis (LDA) was used to classify seizure outcome by temporal lobe volumes and normalized brain volume. RESULTS Epilepsy patients showed normal to small brain volumes and small temporal lobes bilaterally. A multivariate measure of the volume of each temporal lobe separated patients who were seizure free (Engel Class IA) from those with incomplete seizure control (Engel Class IB/IIB) with LDA (p < 0.01). Temporal lobe volumes also separate normal subjects, patients with Engel Class IA outcomes, and patients with Class IB/IIB outcomes (p < 0.01). Additionally, the authors demonstrated that age-normalized whole brain volume, in combination with temporal lobe volumes, may further improve outcome prediction (p < 0.01). CONCLUSIONS This study shows strong evidence that temporal lobe and brain volume can be predictive of seizure outcome following temporal lobe resection, and that volumetric CT analysis of the temporal lobe may be feasible in lieu of structural MRI when the latter is unavailable. Furthermore, since the authors' methods are modality independent, these findings suggest that temporal lobe and normative brain volumes may further be useful in the selection of patients for temporal lobe resection when structural MRI is available.

OBJECT The role of reopening an obstructed endoscopic third ventriculostomy (ETV) as treatment for ETV failure is not well defined. The authors studied 215 children with ETV closure who underwent successful repeat ETV to determine the indications, long-term success, and factors affecting outcome. METHODS The authors retrospectively reviewed the CURE Children's Hospital of Uganda database from August 2001 through December 2012, identifying 215 children with failed ETV (with or without prior choroid plexus cauterization [CPC]) who underwent reopening of an obstructed ETV stoma. Treatment survival according to sex, age at first and second operation, time to failure of first operation, etiology of hydrocephalus, prior CPC, and mode of ETV obstruction (simple stoma closure, second membrane, or cisternal obstruction from arachnoid scarring) were assessed using the Kaplan-Meier survival method. Survival differences among groups were assessed using log-rank and Wilcoxon methods and a Cox proportional hazards model. RESULTS There were 125 boys and 90 girls with mean and median ages of 229 and 92 days, respectively, at the initial ETV. Mean and median ages at repeat ETV were 347 and 180 days, respectively. Postinfectious hydrocephalus (PIH) was the etiology in 126 patients, and nonpostinfectious hydrocephalus (NPIH) in 89. Overall estimated 7-year success for repeat ETV was 51%. Sex (p = 0.46, log-rank test; p = 0.54, Wilcoxon test), age (< vs > 6 months) at initial or repeat ETV (p = 0.08 initial, p = 0.13 repeat; log-rank test), and type of ETV obstruction (p = 0.61, log-rank test) did not affect outcome for repeat ETV (p values ≥ 0.05, Cox regression). Those with a longer time to failure of initial ETV (> 6 months 91%, 3–6 months 60%, < 3 months 42%, p < 0.01; log-rank test), postinfectious etiology (PIH 58% vs NPIH 42%, p = 0.02; log-rank and Wilcoxon tests) and prior CPC (p = 0.03, log-rank and Wilcoxon tests) had significantly better outcome. CONCLUSIONS Repeat ETV was successful in half of the patients overall, and was more successful in association with later failures, prior CPC, and PIH. Obstruction of the original ETV by secondary arachnoid scarring was not a negative prognostic factor, and should not discourage the surgeon from proceeding. Repeat ETV may be a more durable solution to failed ETV/CPC than shunt placement in this context, especially for failures at more than 3 months after the initial ETV. Some ETV closures may result from an inflammatory response that is less robust at the second operation.

Effective treatment of children with medulloblastoma requires a functioning multi-disciplinary team with adequate neurosurgical, neuroradiological, pathological, radiotherapy and chemotherapy facilities and personnel. In addition the treating centre should have the capacity to effectively screen and manage any tumour and treatment-associated complications. These requirements have made it difficult for many low and middle-income countries (LMIC) centres to offer curative treatment. This article provides management recommendations for children with standard-risk medulloblastoma (localised tumours in children over the age of 3-5 years) according to the level of facilities available.

There have been previous reports of intra-scapular limbs associated with a closed spina bifida and this has led to a causative theory. It is thought that these dysraphic appendages could not occur with defects of primary neurulation. The authors present a rare case of this abnormality associated with a large open myelomeningocele in a 6-day-old infant presenting to a paediatric neurosurgical hospital in Uganda. The appendage was removed and the spina bifida closed. There was significant stigma associated with such abnormality in this region. The first reported co-existence of these two lesions challenges previously held beliefs regarding the embryological origin of intra-scapular dysraphic appendage.

Object Antibiotic-impregnated shunts have yet to find widespread use in the developing world, largely due to cost. Given potential differences in the microbial spectrum, their effectiveness in preventing shunt infection for populations in low-income countries may differ and has not been demonstrated. This study is the first to compare the efficacy of a Bactiseal shunt system with a non–antibiotic-impregnated system in a developing country. Methods The Bactiseal Universal Shunt (BUS) was placed in 80 consecutive Ugandan children who required a shunt. In this retrospective cohort study, the outcome for that group was compared with the outcome for the immediately preceding 80 consecutive children in whom a Chhabra shunt had been placed. The primary end points were shunt failure, shunt infection, and death. Shunt survival was analyzed using the Kaplan-Meier method. Significance of differences between groups was tested using the log-rank test, chi-square analysis, Fisher's exact test, and t-test. Results There was no difference between groups in regard to age, sex, or etiology of hydrocephalus. Mean follow-up for cases of nonfailure was 7.6 months (median 7.8 months, interquartile range 6.5–9.5 months). There was no significant difference between groups for any end point. The BUS group had fewer infections (4 vs 11), but the difference was not significant (p = 0.086, log-rank test). Gram-positive cocci were the most common culturable pathogens in the Chhabra group, while the only positive culture in the BUS group was a gram-negative rod. Conclusions These results provide equipoise for a randomized controlled trial in the same population and this has been initiated. It is possible that the observed trends may become significant in a larger study. The more complex task will involve determining not only the efficacy, but also the cost-effectiveness of using antibiotic-impregnated shunt components in limited-resource settings.

This study reviews the first operative series of pediatric brain tumors from Uganda, the largest series from Sub-Saharan Africa, and explores the challenges to progress in pediatric neuro-oncology in the region. This is a retrospective operative series of brain tumors in 172 children at Cure Children’s Hospital of Uganda over 10 years. Demographics, clinical presentation, lesion location, histopathology, operative management, and outcome were investigated. Survival was assessed using Kaplan–Meier method. Log-rank test and p value with Bonferroni correction were used to determine significance of survival differences. There were 103 males (59.9 %) and 69 females (40.1 %; mean age at diagnosis 6.5 years with 29 %

Dandy-Walker complex (DWC) is a continuum of congenital anomalies comprising Dandy-Walker malformation (DWM), Dandy-Walker variant (DWV), Blake pouch cyst, and mega cisterna magna (MCM). Hydrocephalus is variably associated with each of these, and DWC-associated hydrocephalus has mostly been treated by shunting, often with 2-compartment shunting. There are few reports of management by endoscopic third ventriculostomy (ETV). This study is the largest series of DWC or DWM-associated hydrocephalus treated by ETV, and the first report of treatment by combined ETV and choroid plexus cauterization (ETV/CPC) in young infants with this association.A retrospective review of the CURE Children's Hospital of Uganda clinical database between 2004 and 2010 identified 45 patients with DWC confirmed by CT scanning (25 with DWM, 17 with DWV, and 3 with MCM) who were treated for hydrocephalus by ETV/CPC. Three were excluded because of other potential causes of hydrocephalus (2 postinfectious and 1 posthemorrhagic).The median age at treatment was 5 months (88% of patients were younger than 12 months). There was a 2.4:1 male predominance among patients with DWV. An ETV/CPC (ETV only in one) was successful with no further operations in 74% (mean and median follow-up 24.2 and 20 months, respectively [range 6-65 months]). The rate of success was 74% for DWM, 73% for DWV, and 100% for MCM; 95% had an open aqueduct, and none required posterior fossa shunting.Endoscopic treatment of DWC-associated hydrocephalus should be strongly considered as the primary management in place of the historical standard of creating shunt dependence.

Infantile hydrocephalus in East Africa is predominantly postinfectious. The microbial origins remain elusive, since most patients present with postinfectious hydrocephalus after antecedent neonatal sepsis (NS) has resolved.To characterize this syndrome in Ugandan infants, the authors used polymerase chain reaction targeting bacterial 16S ribosomal DNA from CSF to determine if bacterial residua from recent infections were detectable. Bacteria were identified based on the relationship of genetic sequences obtained with reference bacteria in public databases. The authors evaluated samples from patients presenting during dry and rainy seasons and performed environmental sampling in the villages of patients.Bacterial DNA was recovered from 94% of patients. Gram-negative bacteria in the phylum Proteobacteria were the most commonly detected. Within this phylum, Gammaproteobacteria dominated in patients presenting after infections during the rainy season, and Betaproteobacteria was most common following infections during the dry season. Acinetobacter species were identified in the majority of patients admitted after rainy season infection.Postinfectious hydrocephalus in Ugandan infants appears associated with predominantly enteric gram-negative bacteria. These findings highlight the need for linking these cases with antecedent NS to develop more effective treatment and prevention strategies.

The ETV+CPC technique has permeated from CURE Hospital in Uganda to North America and neurosurgeons have travelled to Uganda to learn the nuisances of this technique. The goal of this study was to determine current attitudes of North American pediatric neurosurgeons towards ETV+CPC and the effects of training at CURE on attitude and clinical practice.