Association of cerebrospinal fluid parameters with treatment and complications among children with cerebrospinal fluid shunt infections: a multicenter study.

OBJECTIVE: Cerebrospinal fluid (CSF) white blood cell (WBC) count, neutrophil percentage, protein concentration, and glucose level are typically measured at diagnosis and serially during the treatment of CSF shunt infections. The objective of this retrospective cohort study was to describe the longitudinal profile of CSF parameters in children with CSF shunt infections and assess their association with treatment and outcome. METHODS: Participants were children treated at 11 tertiary pediatric hospitals in Canada and the United States for CSF shunt infection, from July 1, 2013, through June 30, 2019, with hardware removal, external ventricular drain placement, intravenous antibiotics, and subsequent permanent shunt reinsertion. The relationship between CSF parameters and a complicated course (a composite outcome representing children with at least one of the following: contiguous soft-tissue infection, worsening hydrocephalus, CSF leak, intracranial bleed, brain abscess, venous thrombosis, reinfection after insertion of the new shunt, other complication, ICU admission, or death) was analyzed. RESULTS: A total of 109 children (median age 2.8 years, 44% female) were included in this study. CSF pleocytosis, elevated protein, and hypoglycorrhachia had sensitivities of 69%, 47%, and 38% for the diagnosis of culture-confirmed CSF shunt infection, respectively. The longitudinal profile of the neutrophil percentage followed a monotonic trend, decreasing by 1.5% (95% CI 1.0%-2.0%, p < 0.0001) per day over the course of treatment. The initial WBC count differed significantly between pathogens (p = 0.011), but the proportion of neutrophils, protein concentration, and glucose level did not, and was lowest with Cutibacterium acnes. The duration of antibiotic treatment and the time to shunt reinsertion were longer in patients with a higher initial neutrophil percentage. Fifty-eight patients (53%) had one or more complications during their admission. A neutrophil percentage > 44% (Youden index) in the initial CSF sample was associated with a 1.8-fold (95% CI 1.2- to 2.8-fold) higher relative risk of a complicated course. In a random-intercept, random-slope linear mixed-effects model, the longitudinal neutrophil trajectory differed significantly between patients with and without complications (p = 0.030). CONCLUSIONS: A higher proportion of neutrophils in the CSF at diagnosis was associated with a complicated clinical course. Other CSF parameters were associated with treatment and outcome; however, wide variability in values may limit their clinical utility.

Maternal and childhood medical history and the risk of childhood brain tumours: a case-control study in Ontario, Canada.

BACKGROUND: Studies to date have yielded inconclusive results as to whether maternal medical history during pregnancy, and a child's early-life medical history contribute to the development of childhood brain tumours (CBTs). This study examined associations between maternal and childhood medical history and the risk of CBTs. METHODS: The Childhood Brain Tumour Epidemiology Study of Ontario (CBREO) examined children 0-15 years of age with newly diagnosed CBTs from 1997 to 2003. Multivariable logistic regression analysis determined associations for prenatal medications and childhood medical history, adjusted for child's demographics, and maternal education. Analyses were stratified by histology. A latency period analysis was conducted using 12- and 24-month lead times. RESULTS: Maternal intake of immunosuppressants during the prenatal period was significantly associated with glial tumours (OR 2.73, 95% CI 1.17-6.39). Childhood intake of anti-epileptics was significantly associated with CBTs overall, after accounting for 12-month (OR 8.51, 95% CI 3.35-21.63) and 24-month (OR 6.04, 95% CI 2.06-17.70) lead time before diagnosis. No associations for other medications were found. CONCLUSIONS: This study underscores the need to examine potential carcinogenic effects of the medication classes highlighted and of the indication of medication use. Despite possible reverse causality, increased CBT surveillance for children with epilepsy might be warranted.

Cerebrospinal Fluid Shunt Infections: A Multicenter Pediatric Study.

BACKGROUND: Infections complicate 5%-10% of cerebrospinal fluid (CSF) shunts. We aimed to describe the characteristics and contemporary pathogens of shunt infections in children in Canada and the United States. METHODS: Descriptive case series at tertiary care hospitals in Canada (N = 8) and the United States (N = 3) of children up to 18 years of age with CSF shunt infections from July 1, 2013, through June 30, 2019. RESULTS: There were 154 children (43% female, median age 2.7 years, 50% premature) with ≥1 CSF shunt infections. Median time between shunt placement and infection was 54 days (interquartile range, 24 days-2.3 years). Common pathogens were coagulase-negative staphylococci (N = 42; 28%), methicillin-susceptible Staphylococcus aureus (N = 24; 16%), methicillin-resistant S. aureus (N = 9; 5.9%), Pseudomonas aeruginosa (N = 9; 5.9%) and other Gram-negative bacilli (N = 14; 9.0%). Significant differences between pathogens were observed, including timing of infection (P = 0.023) and CSF leukocyte count (P = 0.0019); however, differences were not sufficient to reliably predict the causative organism based on the timing of infection or discriminate P. aeruginosa from other pathogens based on clinical features. Empiric antibiotic regimens, which included vancomycin (71%), cefotaxime or ceftriaxone (29%) and antipseudomonal beta-lactams (33%), were discordant with the pathogen isolated in five cases. There was variability between sites in the distribution of pathogens and choice of empiric antibiotics. Nine children died; 4 (44%) deaths were attributed to shunt infection. CONCLUSIONS: Staphylococci remain the most common cause of CSF shunt infections, although antibiotic resistant Gram-negative bacilli occur and cannot be reliably predicted based on clinical characteristics.

Childhood head trauma and the risk of childhood brain tumours: A case-control study in Ontario, Canada.

Head trauma in early childhood has been hypothesized as a potential risk factor for childhood brain tumours (CBTs). However, head trauma has not been extensively studied in the context of CBTs and existing studies have yielded conflicting results. A population-based and hospital-based case-control study of children 0 to 15 years with newly diagnosed CBTs from 1997 to 2003 recruited across Ontario through paediatric oncology centres was conducted. Controls were frequency-matched with cases by age, sex and geographical region. The association was assessed based on multivariable logistic regressions, accounting for child's age, sex, ethnicity, highest level of maternal education and maternal pack-years of smoking during the pregnancy. Analyses were conducted separately based on age of first head trauma, sex and histology. A latency period analysis was conducted. Overall, based on 280 cases and 919 controls, CBTs were not significantly associated with previous history of head trauma (OR 1.34, 95% CI 0.96, 1.86), head trauma severity, number of head injuries, or head or neck X-rays or computed tomography (CT) examinations. Results were consistent across sexes and histological subtypes. However, head trauma within the first year of life was significantly associated with CBTs (OR 2.00, 95% CI 1.01, 3.98), but the association diminished when adjusted for X-ray or CT occurring during the same time period (OR 1.62, 95% CI 0.75, 3.49), albeit limited sample size. Overall, no association was observed between head trauma and CBTs among all children, while head trauma occurring within first year of life may warrant further investigation in future research.

Effects of systemic corticosteroid treatment on pseudotumoral hemicerebellitis: a case report and literature review.

PURPOSE: Pseudotumoral hemicerebellitis is an acute, unilateral inflammation of the cerebellum that typically affects the pediatric population. The purpose of this paper is to review cases of pseudotumoral hemicerebellitis in the literature and evaluate if treatment with systemic corticosteroids reduces length of time to symptomatic recovery. METHODS: We present a case report of a 12-year-old male with pseudotumoral hemicerebellitis and unilateral cerebellar dysfunction. Additionally, we review the thirty-five reported cases of pseudotumoral hemicerebellitis with respect to length of time to symptomatic recovery with or without systemic corticosteroid treatment. RESULTS: Thirty cases reported length of time to symptomatic recovery. Including our case, the mean time to recovery for those treated with systemic corticosteroids (n = 20) was 48.05 days (SE = 16.3). The mean time to recovery for those treated without (n = 10) was 86.7 days (SE = 29.3). CONCLUSIONS: Treatment with systemic corticosteroids was associated with a faster time to symptomatic recovery compared to without. Regardless of etiology, reducing inflammation and mass effect involved in pseudotumoral hemicerebellitis may be integral to a more rapid return to neurological baseline.

Collection and Analyses of Cerebrospinal Fluid for Pediatric Translational Research.

Cerebrospinal fluid sample collection and analysis is imperative to better elucidate central nervous system injury and disease in children. Sample collection methods are varied and carry with them certain ethical and biologic considerations, complications, and contraindications. Establishing best practices for sample collection, processing, storage, and transport will ensure optimal sample quality. Cerebrospinal fluid samples can be affected by a number of factors including subject age, sampling method, sampling location, volume extracted, fraction, blood contamination, storage methods, and freeze-thaw cycles. Indicators of sample quality can be assessed by matrix-associated laser desorption/ionization time-of-flight mass spectrometry and include cystatin C fragments, oxidized proteins, prostaglandin D synthase, and evidence of blood contamination. Precise documentation of sample collection processes and the establishment of meticulous handling procedures are essential for the creation of clinically relevant biospecimen repositories. In this review we discuss the ethical considerations and best practices for cerebrospinal fluid collection, as well as the influence of preanalytical factors on cerebrospinal fluid analyses. Cerebrospinal fluid biomarkers in highly researched pediatric diseases or disorders are discussed.

Congenital Calvarial Hemangioma.

OBJECTIVES: The authors describe a case of congenital calvarial hemangioma successfully managed using propranolol therapy. Presenting symptoms, radiological and pathological features, differential diagnosis, and management of this rare congenital mass are described. CASE PRESENTATION: A 2-year-old boy presented with a 1-year history of a growing right parietal skull mass. No obvious etiology was apparent. No focal neurological deficits or associated craniofacial anomalies were identified. Plain film imaging demonstrated focal thickening of the right parietal bone with internal trabeculations in a sunburst appearance. Computed tomography (CT) scan showed bone thickening with coarsening of the bony trabeculae, minor irregularity of the outer table, unaffected inner table, and no evidence of aggressive features. A diagnostic biopsy of the lesion was performed in the operating room. Microscopic examination was consistent with hemangioma. Based on histological and radiological features of the lesion, it was identified as a cavernous hemangioma. Medical treatment utilizing propranolol was initiated for over 3 years with interval reduction in the lesion size. MRI head following treatment with propranolol demonstrated reduction of the mass compared to preoperative imaging. CONCLUSIONS: Although a rare entity, it is important to consider congenital calvarial hemangioma in the differential diagnosis of slow growing skull lesions due to the possibility of complications as a result of the hemangioma's intracranial extension, and the potential for treatment. En bloc resection has classically been described as a treatment for such lesions, although our case demonstrates that medical treatment with propranolol therapy may be appropriate in certain situations.

Infected cephalohematomas and underlying osteomyelitis: a case-based review.

BACKGROUND: Cephalohematomas are relatively common sub-periosteal collections of blood that tend to resolve spontaneously without treatment. Rarely, they become infected and can be associated with underlying osteomyelitis, meningitis, or sepsis. Common pathogens include Escherichia coli and Staphylococcus species. ILLUSTRATIVE CASE: This report describes the first case of a neonate developing an infected right parietal cephalohematoma and underlying osteomyelitis caused by Morganella morganii, which was cultured in blood and cephalohematoma aspirate. This infant male, whose risk factors included vacuum extraction during delivery and suspected post-natal pneumonia, responded well to a 6-week course of intravenous meropenem with complete resolution of both lesions. CONCLUSION: When an infected cephalohematoma is suspected, aspiration of hematoma fluid should be performed for both diagnostic and therapeutic purposes. Infectious symptoms should warrant prompt investigation and treatment, which may include drainage, debridement, and antibiotics. This report demonstrates that the combination of an infected cephalohematoma and underlying osteomyelitis might not be as uncommon as previously believed.

Pediatric thalamic tumors in the MRI era: a Canadian perspective.

BACKGROUND: Thalamic gliomas are rare. The natural history is unpredictable, and the optimal management of these tumors in children is poorly defined. The aim was to identify outcomes, prognostic factors, and response to various modalities of treatment in a relatively large population of pediatric thalamic tumors from many centers within a fairly homogeneous health care system. METHODS: We performed a Canadian multicenter retrospective review of pediatric thalamic tumors presenting during the MRI era (1989-2012). Radiology and pathology were reviewed by central independent reviewers. Paraffin shavings for RNA extraction were taken and tested for fusion events involving KIAA1549:BRAF. Tumors were classified as unilateral or bithalamic based on their origin on imaging. Univariate and multivariate analyses on factors influencing survival were performed. RESULTS: Seventy-two thalamic tumors were identified from 11 institutions. Females represented 53% of the study population, and the mean age at presentation was 8.9 years. Sixty-two tumors were unilateral and 10 bithalamic. Unilateral tumors had a greater propensity to grow inferiorly towards the brainstem. These tumors were predominantly low grade in comparison to bithalamic tumors which were high-grade astrocytomas. The 5-year overall survival was 61 ± 13% for unithalamic tumors compared to 37 ± 32% for bithalamic tumors (p = 0.097). Multivariate analysis indicated tumor grade as the only significant prognostic factor for unithalamic tumors. Six unilateral tumors, all low grade, were BRAF fusion positive. CONCLUSION: Unilateral and bilateral thalamic tumors behave differently. Surgical resection is an appropriate treatment option in unilateral tumors, most of which are low grade, but outcome is not related to extent of resection (EOR). Bilateral thalamic tumors have a poorer prognosis, but the occasional patient does remarkably well. The efficacy of chemotherapy and radiotherapy has not been clearly demonstrated. Novel therapeutic approaches are required to improve the prognosis for malignant unilateral thalamic tumors and bilateral thalamic tumors.

Basal skull fractures are associated with mortality in pediatric severe traumatic brain injury.

BACKGROUND: Basal skull fractures (BSFs) are caused by blunt force trauma, occurring in the temporal, occipital, sphenoid, and/or ethmoid bones. In pediatric severe traumatic brain injury (sTBI), there is a paucity of data on BSFs. Our goal was to investigate the BSF prevalence, anatomy, and association with short-term outcomes in pediatric sTBI. METHODS: We retrospectively reviewed all severely injured (Injury Severity Score ≥12) pediatric patients (aged <18 years) admitted to our hospital after experiencing an sTBI (Glasgow Coma Scale score ≤8 and head Abbreviated Injury Scale score ≥4). Neuroimaging for all sTBI patients was reviewed for skull fractures. Data were analyzed with both univariate and multivariate techniques. RESULTS: Of the 180 patients with sTBI, 47 had BSFs for a prevalence of 26% (69 BSFs in total; 16 sTBI patients had ≥2 BSFs). The squamous temporal bone was fractured most frequently (n=30/47 sTBI patients with BSFs). Patients with BSFs were heavier and had more facial injuries than those without (p < 0.05) but were similar in all other admission demographics, injury profiles, and clinical characteristics. Cerebrospinal fluid leak was found in 32% (n = 15 of 47) of BSF patients (otorrhea, n = 12; rhinorrhea, n = 1; otorrhea/rhinorrhea, n = 2; p < 0.001). Mortality, acute central diabetes insipidus, and fewer ventilator-free days were associated with BSFs (p < 0.005), whereas in sTBI survivors, BSFs were associated with longer lengths of stay (p < 0.05). Multiple logistic regression showed that BSFs were positively associated with the presence of subarachnoid hemorrhage (odds ratio [OR], 4.00; p = 0.001), contusion (OR, 2.48; p = 0.029), herniation (OR, 3.40; p = 0.037), and cerebral edema (OR, 2.30; p = 0.047) but negatively associated with diffuse axonal injury (OR, 0.20; p = 0.003). BSFs and mortality were strongly associated (OR, 6.87; p = 0.019). CONCLUSION: BSFs occurred in 26% of pediatric sTBI patients. The temporal bone was fractured in two thirds of sTBI patients with BSFs, and one third was associated with cerebrospinal fluid leaks. BSFs represent a significant linear blunt force and are independent predictors of mortality. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.

Seizures in children with dysembryoplastic neuroepithelial tumors of the brain--A review of surgical outcomes across several studies.

PURPOSE: In children and adolescents, dysembryoplastic neuroepithelial tumors (DNETs) of the brain present with seizures almost 100% of the time, potentially creating significant long-term morbidity and disability despite the generally indolent course of the lesion. These tumors also tend to be quite resistant to anti-epileptic drugs which, themselves, can be associated with long-term side effects and resultant disability. Many clinicians advocate early surgical resection of these lesions, but how effective this approach is, and how aggressive tumor removal should be, continues to be debated. METHODS: We performed a systematic review of the relevant literature to identify all reports of DNET resections in pediatric patients published over the past 20 years. In all, over 3000 MEDLINE abstracts were reviewed, ultimately resulting in 13 studies with 185 pediatric DNET patients to review. RESULTS: Surgical resection of the lesion was effective at improving seizures in over 98% of patients and at achieving long-term seizure freedom in 86%. Surgical resection of DNETs also appeared to be quite safe, with no reported perioperative deaths and an overall rate of postoperative complications of 12%; the vast majority of these complications were transient. CONCLUSIONS: Total gross resection of the lesion was the only factor statistically correlated with long-term seizure freedom (r = 0.63, p = 0.03). However, data remain lacking regarding whether this translates into more extensive procedures-like brain mapping and partial lobectomies-being any more effective than simple lesionectomies alone. Further research is clearly needed to address this and other crucial questions.

Subarachnoid hemorrhage prevalence and its association with short-term outcome in pediatric severe traumatic brain injury.

BACKGROUND: Subarachnoid hemorrhage (SAH) is an independent prognostic indicator of outcome in adult severe traumatic brain injury (sTBI). There is a paucity of investigations on SAH in pediatric sTBI. The goal of this study was to determine in pediatric sTBI patients SAH prevalence, associated factors, and its relationship to short-term outcome. METHODS: We retrospectively analyzed 171 sTBI patients (pre-sedation GCS ≤8 and head MAIS ≥4) who underwent CT head imaging within the first 24 h of hospital admission. Data were analyzed with both univariate and multivariate techniques. RESULTS: SAH was found in 42 % of sTBI patients (n = 71/171), and it was more frequently associated with skull fractures, cerebral edema, diffuse axonal injury, contusion, and intraventricular hemorrhage (p < 0.05). Patients with SAH had higher Injury Severity Scores (p = 0.032) and a greater frequency of fixed pupil(s) on admission (p = 0.001). There were no significant differences in etiologies between sTBI patients with and without SAH. Worse disposition occurred in sTBI patients with SAH, including increased mortality (p = 0.009), increased episodes of central diabetes insipidus (p = 0.002), greater infection rates (p = 0.002), and fewer ventilator-free days (p = 0.001). In sTBI survivors, SAH was associated with increased lengths of stay (p < 0.001) and a higher level of care required on discharge (p = 0.004). Despite evidence that SAH is linked to poorer outcomes on univariate analyses, multivariate analysis failed to demonstrate an independent association between SAH and mortality (p = 0.969). CONCLUSION: SAH was present in almost half of pediatric sTBI patients, and it was indicative of TBI severity and a higher level of care on discharge. SAH in pediatric patients was not independently associated with increased risk of mortality.

Familial syndromes associated with intracranial tumours: a review.

BACKGROUND: Most cancers of the central nervous system (CNS) occur sporadically in the absence of any known underlying familial disorder or multi-systemic syndrome. Several syndromes are associated with CNS malignancies, however, and their recognition has significant implications for patient management and prognosis. Patients with syndrome-associated CNS malignancies often have multiple tumours (either confined to one region or distributed throughout the body), with similar or different histology. OBJECTIVE: This review examines syndromes that are strongly associated with CNS cancers: the phakomatosis syndromes, familial syndromes such as Li-Fraumeni and familial polyposis syndromes and dyschondroplasia.

Brainstem cavernoma hemorrhage during pregnancy in a 15-year-old: description of a unique neurosurgical approach.

Cavernous haemangiomas, or cavernous malformations, have been reported during pregnancy, most of which have been either supratentorial or spinal lesions. We encountered a 15-year old pregnant patient with a rapidly progressive and haemorrhagic brainstem cavernous haemangioma. The case presented here describes the history and findings of this patient, as well as the less-commonly utilized technique we used to access the floor of the fourth ventricle via occipital craniotomy for complete macroscopic resection of this lesion, resulting in the gradual return of most of her neurological deficits.

Incidence of major and minor brain injuries in facial fractures.

BACKGROUND: Facial fractures can be associated with brain and cervical spine injuries because impact forces are transmitted through the head and neck. Although major brain injury is commonly recognized in these patients, incidence of minor brain injury is not well-known, despite potential morbidity and mortality. OBJECTIVES: This prospective study aimed to determine the incidence of both major and minor brain injuries in 100 patients presenting to a craniofacial surgery service with facial fractures and to identify characteristics associated with brain injury. METHODS: Data were collected for a 9-month period by a craniofacial surgeon at a level I trauma center. A questionnaire and checklist were designed to capture information about major and minor brain injury in patients with facial fractures. Assessments were completed in the outpatient clinic, emergency department, hospital ward, or intensive care unit during the first patient encounters. RESULTS: The average age of patients was 34 years; 79% were male. Time between injury and assessment ranged from less than a few hours to 4 months. Incidence of brain injury was 67% overall: 29% with major brain injury and 38% with minor injury. Major brain injury was commonly diagnosed early in the emergency department or intensive care unit. Conversely, minor brain injury tended to be diagnosed late in the clinic. Patient age, mechanism of injury, and type of facial fracture predicted brain injuries overall, but mechanism of injury was the sole predictor of minor brain injury. CONCLUSIONS: Facial fractures are often associated with brain injury. A high level of suspicion is warranted for minor traumatic brain injuries.

Central pontine and extrapontine myelinolysis in children: a review of 76 patients.

This study aimed to identify the causes and contributing factors, neurologic presentation, and outcomes of central pontine and extrapontine myelinolysis and to examine any trends in the presentation and course of these disorders over the past 50 years. Seventy-six pediatric cases were identified in the literature. Age, sex, decade of diagnosis, neurologic presentation, outcome, and attributed causes were extracted. The results showed that the diagnosis, course, and outcomes of central pontine and extrapontine myelinolysis clearly have changed over the past few decades. Early cases generally were diagnosed at autopsy as opposed to computed tomography or magnetic resonance imaging more recently. Ninety-four percent of cases prior to 1990 and only 7% of cases from 1990 onward resulted in patient mortality. The decade in which the case was reported was the strongest predictor of outcome (P < .001), followed by sodium dysregulation (P = .045) and dehydration (P = .07).

Acute cranial decompression in Meckel-Gruber syndrome and slit-ventricle syndrome with craniocephalic disproportion.

Slit-ventricle syndrome (SVS) is characterized by headaches associated with subnormal ventricular size in patients with shunt-treated hydrocephalus. It commonly occurs in children who have had shunts placed at an early age and is diagnosed when computed tomography scans are carried out to investigate suspected shunt obstruction with an accompanying rise in intracranial pressure (ICP). Overdrainage of cerebrospinal fluid may additionally result in craniocephalic disproportion, potentially by dampening the normal expansile pulsations of the dura against the skull, which leads to craniostenosis. Management is controversial because many strategies have only short-term benefit, and surgical intervention is understandably often seen as a last resort.We present a case of a child with SVS and craniocephalic disproportion who was treated with urgent cranial expansion due to rising ICP. Intraoperative ICP monitoring demonstrates a rapid and sustained drop in ICP, and the patient made an uneventful return to his premorbid condition. We conclude that cranial vault expansion should be considered as an effective treatment for postshunt craniocephalic disproportion in patients with SVS.

When only partial spinal cord detethering is possible.

In most instances, initial surgery to untether a tethered spinal cord is successful. But what happens when it is not? The authors describe the case of a now 18-year-old woman with spina bifida in whom surgery for tethered cord was required on two occasions. In both instances, due to the extent of her underlying lesion and fibrous tissue, only partial detethering was possible without acutely sacrificing significant neurological function. The authors detail the patient's course and review the peer-reviewed scientific literature on outcomes in patients in whom only partial cord detethering is achieved. In their review of all case series and clinical studies pertaining to the surgical treatment of tethered cord syndrome identified during an online search of 2184 scientific abstracts and 2 major neurosurgery textbooks, excluding the present case, the authors identified 53 confirmed or presumed cases of incomplete detethering in eight articles, incorporating 390 patients, for an overall prevalence of roughly 13.6%. Although no investigators have reported statistical comparisons of outcomes in those in whom just partial and complete detethering has been achieved, the evidence generally suggests poorer outcomes in the former. Prospective multicenter studies addressing this important issue clearly are warranted. To date, the authors believe that incomplete detethering is grossly underreported in the medical literature.