Comparison of Shunt Outcomes for Nonbacterial Infection Hydrocephalus with Common Hydrocephalus Etiologies: A Retrospective Case-Control Study.

BACKGROUND: Shunting is an established treatment for hydrocephalus, yet reports on shunt outcomes for nonbacterial infection (NBI) hydrocephalus are limited. Furthermore, comparison of mechanisms and rates of failure for shunted NBI hydrocephalus versus more typical etiologies remains undetermined. METHODS: Patients who underwent shunting for hydrocephalus at 2 centers (1995-2020) were included. Indications for shunting were grouped as "typical" (congenital, posthemorrhagic, normal pressure hydrocephalus, malignancy-related, trauma, and idiopathic) and NBI hydrocephalus (coccidioidomycosis, cryptococcosis, and neurocysticercosis). Rates of shunt malfunction were compared. RESULTS: There were 261 patients shunted for typical hydrocephalus (48.7% male; age = 50.7 ± 21.7) and 93 patients for NBI hydrocephalus (72.0% male; age = 41.8 ± 13.2). For patients with typical hydrocephalus, 29.5% required ≥1 shunt revision, compared with 64.5% with NBI hydrocephalus (P < 1E-5). Of those with malfunction, NBI shunts required more revision operations (median = 3.0; max = 21) than typical shunts (median = 2.0; max = 6; P < 0.05). The censored median time to shunt failure for NBI hydrocephalus was 26.9 months and was not reached for typical etiologies by 180 months. Multivariate analysis showed shunts for NBI hydrocephalus were significantly more likely to fail (hazard ratio = 2.25; 95% confidence interval = 1.58-3.19). A distal pseudocyst was implicated in 30.0% and 2.6% of shunt failures for NBI and typical hydrocephalus, respectively (P < 1E-5). Sixteen (26.7%) NBI shunt failures required revision to lower-resistance systems compared to 6 (7.8%) typical failures (P < 0.05). CONCLUSIONS: Shunts placed for hydrocephalus secondary to nonbacterial infections are complicated by significantly higher rates of malfunction. These patients are prone to develop distal abdominal pseudocysts and often require revision to low-resistance systems.

Recurrent neonatal sepsis and progressive white matter injury in a premature newborn culture-positive for group B Streptococcus: A case report.

RATIONALE: Group B Streptococcus (GBS) remains a principal pathogen causing neonatal sepsis and meningitis, particularly in premature infants with relatively insufficient immunity. Recurrence may occur uncommonly, largely associated with subclinical mucosal persistence or repetitive exposure to exogenous sources. White matter injury (WMI) including cystic periventricular leukomalacia (PVL) has been associated with intrauterine infection/inflammation, and neonatal infection as a more significant predictor including postnatal sepsis and recurrent infection, even without microbial neuroinvasion. Furthermore, clinical and experimental evidence of WMI by some bacteria other than GBS without central nervous system invasion has been reported. However, there is little evidence of WMI associated with neonatal GBS sepsis in the absence of meningitis in the literature. PATIENT CONCERNS: A newborn at 30+4 weeks' gestation with low birthweight presented with 2 episodes (with a 13-day interval with no antibiotic therapy) of neonatal sepsis culture-proven for GBS with early-onset presentation after clinical chorioamnionitis via vertical GBS transmission and the associated conditions including prematurity-related neonatal immunodeficiency and persistent mucosal GBS carriage after the first antibiotic treatment. The perinatal GBS infection was complicated by progressive WMI presenting with ventriculomegaly and cystic PVL without a definite evidence of meningitis, intraventricular hemorrhage, and documented cerebral hypoxia or hypoperfusion conditions including septic shock. DIAGNOSES: Recurrent group B streptococcal sepsis and cystic PVL with ventriculomegaly. INTERVENTIONS: Two episodes of GBS sepsis were treated with 15-day parenteral antibiotic therapy, respectively. OUTCOMES: Resolution of the recurrent GBS sepsis without further relapses, however, complicated by WMI and subsequent about 6 months delay in motor development at 12 months' corrected age. LESSONS: This case suggests WMI associated with GBS bacteremia without central nervous system entry by viable GBS and also shows that in premature infants, intrauterine GBS infection with no interventions may lead to extensive and persistent GBS colonization, early-onset and recurrent GBS disease, and WMI. Postnatal as well as intrauterine infection/inflammation controls with maternal prophylaxis may be pivotal for prevention and limiting the magnitude of neurologic injury.

An atlas overview of characteristic features of tuberculosis that may be encountered at autopsy.

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis. Although primarily a disease of the respiratory system it may be found in any organ or tissue. Global population movements and the emergence of resistant strains are contributing to increasing numbers of cases in certain populations. Subtlety of symptoms and signs, chronicity of disease and failure to seek medical assistance may result in the diagnosis only being made at the time of autopsy. For this reason forensic pathologists need to understand the protean manifestations of the disease and the variable mechanisms by which TB may cause death. This atlas overview provides descriptions of the pathological manifestations of TB in a variety of organs with accompanying illustrations. It serves as a summary of conditions that should be checked for at autopsy in suspected or confirmed cases.

HIV-Negative Cryptococcal Meningoencephalitis Results in a Persistent Frontal-Subcortical Syndrome.

Twenty-seven previously healthy (of 36 consecutive eligible patients), HIV-negative cryptococcal meningoencephalitis (CM) patients underwent comprehensive neuropsychological evaluation during the late post-treatment period (1.3-4 years post diagnosis), assessing attention, language, learning, memory, visuospatial, executive function, information processing, psychomotor functioning, as well as mood symptoms. Seven of eight domains (all except attention) showed increased percentages of CM patients scoring in the less than 16th percentile range compared to standardized normative test averages, adjusted for education level and age. Comparison with a matched archival dataset of mild cognitive impairment/Alzheimer's disease patients showed that CM patients exhibited relative deficits in psychomotor and executive function with fewer deficits in memory and learning, consistent with a frontal-subcortical syndrome. MRI evaluation at the time of testing demonstrated an association of lower neuropsychological functioning with ventriculomegaly. These studies suggest that CM should be included in the list of treatable causes of dementia in neurological work ups. Future studies are needed to identify diagnostic and treatment regimens that may enhance neurological function after therapy.

Efficacy of ventriculoperitoneal shunting in patients with cryptococcal meningitis with intracranial hypertension.

BACKGROUND: Ventriculoperitoneal (VP) shunting in cryptococcal meningitis (CM) patients with high intracranial pressure (ICP) has been studied extensively. METHODS: A total of 74 CM patients with ICP were identified, including 27 patients with or without ventriculomegaly receiving VP shunting. RESULTS: Through retrospective analysis, there was an obvious decline in ICP as well as Cryptococcus count after VP shunting. Damage to the cranial nerves was improved after the surgery. For those patients receiving VP shunting, there was an obvious decline in ICP as well as Cryptococcus count, with less usage of mannitol. Hydrocephalus or ventriculomegaly was improved, and both the clearance time of Cryptococcus and the hospitalization time were shortened (p<0.05). The complications of VP shunting were not common. CONCLUSIONS: For patients diagnosed with CM and with apparent ICP, VP shunting can be considered regardless of whether there is damage to the cranial nerves or hydrocephaly.

Intracranial Fungal Infection After Solid-Organ Transplant.

Neurologic complications after solid-organ transplant reveal a great spectrum of pathologies. Intracranial hemorrhages, cerebral ischemic lesions, infarctions, lymphoproliferative disorders, and infections, including aspergillosis, have been observed after liver transplant. Fungi constitute nearly 5% of all central nervous system infections, mainly occurring in immunocompromised patients. The most common causative agent is Aspergillus species. It presents either as maxillary sinusitis or pulmonary infection. Brain involvement of Aspergillus carries a high rate of mortality. Aspergillosis presents in the forms of meningitis, mycotic aneurysms, infarctions, and mass lesions. Aspergillosis does not have a specific radiologic appearance. Parenchymal aspergillosis has heterogenous signal intensity (hypointense on T1-weighted and hyperintense on T2-weighted images). Here, we present 3 patients who underwent solid-organ transplant and developed central nervous system aspergillosis. Different modalities of neurosurgical intervention were performed in combination with chemotherapy as part of their fungal therapy.

Biomarkers of Cerebral Injury and Inflammation in Pediatric Tuberculous Meningitis.

Background: Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neurospecific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome. Methods: Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analyzed for the neuromarkers S100B, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), in addition to multiple inflammatory markers. Results were compared with 2 control groups: patients with (1) a fatty filum (abnormal filum terminale of the spinal cord); and (2) pulmonary tuberculosis (PTB). Imaging was conducted on admission and at 3 weeks. Outcome was assessed at 6 months. Results: Data were collected from 44 patients with TBM (cases; median age, 3.3 [min-max 0.3-13.1] years), 11 fatty filum controls (median age, 2.8 [min-max 0.8-8] years) and 9 PTB controls (median age, 3.7 [min-max 1.3-11.8] years). Seven cases (16%) died and 16 (36%) had disabilities. Neuromarkers and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and NSE were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE, and GFAP. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased. Cerebral infarcts were associated with highest overall neuromarker concentrations and an increasing profile over time. Tuberculomas were associated with elevated interleukin (IL) 12p40, interferon-inducible protein 10, and monocyte chemoattractant protein 1 concentrations, whereas infarcts were associated with elevated tumor necrosis factor α, macrophage inflammatory protein 1α, IL-6, and IL-8. Conclusions: CSF neuromarkers are promising biomarkers of injury severity and are predictive of mortality. An increasing trend suggested ongoing brain injury, even though markers of inflammation declined with treatment. These findings could offer novel insight into the pathophysiology of TBM.

Ventriculo-peritoneal shunt independence following successful treatment of Gram negative (E. coli) ventriculitis: Case report and review of the literature.

We report a case of tumour-related hydrocephalus in a child treated with a ventriculo-peritoneal shunt which subsequently became infected with gram negative bacteria (Escherichia coli). After successful treatment of the infection the patient became shunt independent and has remained so for over 2 years. Gram negative ventriculitis is associated with diminished cerebro-spinal fluid production and we discuss the literature to date regarding this phenomenon.

Usefulness of McRAPD for typing and importance of biofilm production in a case of nosocomial ventriculoperitoneal shunt infection caused by Candida lusitaniae.

A case report of ventriculoperitoneal shunt infection caused by Candida lusitaniae in a 6-year-old patient with cerebral astrocytoma and obstructive hydrocephalus is presented briefly with emphasis on the course of antifungal treatment. Seven isolates recovered subsequently from the cerebrospinal fluid were studied retrospectively. To confirm identity, isolates were typed using pulsed-field gel electrophoresis and melting curve of random amplified polymorphic DNA (McRAPD). Further, the ability to form biofilm and its susceptibility to systemic antifungals were evaluated. Using McRAPD, identity of C. lusitaniae isolates showing slight microevolutionary changes in karyotypes was undoubtedly confirmed; successful application of numerical interpretation of McRAPD for typing is demonstrated here for the first time. The strain was also recognized as a strong biofilm producer. Moreover, minimum biofilm inhibitory concentrations were very high, in contrast to low antifungal minimum inhibitory concentrations of isolates. It can be concluded that McRAPD seems to be a simple and reliable method not only for identification but also for typing of yeasts. A ventriculoperitoneal shunt colonized by C. lusitaniae was revealed as the source of this nosocomial infection, and the ability of the strain to form biofilm on its surface likely caused treatment failure.

Decisions regarding intracranial complications from acute mastoiditis in children.

PURPOSE OF REVIEW: To review the clinical findings and treatment algorithms for intracranial complications of acute mastoiditis, such as sigmoid sinus thrombosis, otitic hydrocephalus, intracranial abscess, and otitic meningitis. We also briefly discuss the clinical sequelae of these complications. RECENT FINDINGS: Recent changes in the microbiology and treatment paradigms of otitis media have the potential to influence the rates of intracranial complications of mastoiditis; however, evidence supporting a resultant increase in the rates of these complications is lacking. SUMMARY: Antibiotic therapy and myringotomy with ventilation tube placement, with or without mastoidectomy, are the mainstays of treatment for intracranial complications of acute mastoiditis. Adjunct treatment, such as anticoagulation for sigmoid sinus thrombosis, is often used; however, the rarity of these complications makes establishing appropriate levels of evidence to support their use difficult.

Unilateral hydrocephalus: atypical presentation of intracranial tuberculoma.

A 43-year-old male presented with 3-month history of low-grade fever and headache. Radiological investigations revealed unilateral hydrocephalus. Unilateral obstruction of the foramen of Monro due to chronic tubercular ependymal inflammation was suspected and endoscopic septostomy was planned. Though ventriculo-peritoneal shunt is a simple method to treat hydrocephalus, complications related to this procedure are numerous. Neuroendoscopy is a safe method to treat hydrocephalus in selected cases, and also provides access to biopsy the lesion in question. An isolated tuberculoma obstructing the foramen of Monro was seen during endoscopy. Presentation and management of this unusual tuberculoma is reported along with a review of the pertinent literature.

Difficulty diagnosing chronic cryptococcal meningitis in idiopathic CD4+ lymphocytopenia.

A 64-year-old man with idiopathic CD4(+) lymphocytopenia developed cognitive impairment and gait ataxia with isolated obstructive hydrocephalus, which was fatal. Cerebrospinal fluid showed mild pleocytosis, but the etiology was not revealed by extensive analysis. At autopsy, inflammatory cells, CD8(+) lymphocytes and abundant macrophages but not CD4(+) lymphocytes were infiltrating the meninges at the base of the brain. Electron microscopy demonstrated that inflammation was caused by Cryptococcus neoformans, which was localized exclusively within macrophages, where it grew with budding. Our study suggests that, in idiopathic CD4(+) lymphocytopenia, macrophages can efficiently phagocytize but inefficiently digest C. neoformans, thus representing a vehicle of chronic intracellular infection.

Fungal infections of the nervous system: current perspective and controversies in management.

In the last two decades, more elaborative use of intensive care units for serious medical disorders, advancements in transplant procedures and concomitant use of immunosuppressive therapies as well as the pandemic spread of HIV, etc. have increased the incidence of systemic fungal infections, especially life threatening central nervous system (CNS) infections. The CNS fungal infections present with various clinical syndromes: meningitis; encephalitis; hydrocephalus/raised intracranial pressure (raised ICP); space occupying lesions; orbito-rhino-cerebral syndromes; acute cerebro-vascular events and spinal infections. However, the common presentations among these ones are basal meningitis, hydrocephalus, space occupying lesions (cerebral abscesses and granulomas) and stroke syndromes. Clinical picture may mimic tubercular meningitis and therefore, needs careful evaluation. The CNS mycoses carry higher risks of morbidities and mortality as compared to other infective processes and therefore promptly require precise diagnosis and appropriate medical and/or surgical management strategies to optimize the outcome. Among the antifungal drugs, the Amphotericin B had remained first line of therapy for many decades in invasive fungal infections but is not effective in many forms of mycoses. Fortunately, many useful antifungal drugs were introduced during the last two decades. Initially, the lipid based formulations of the Amphotericin B, then the new triazoles and most recently, echinocandins. These medications are used more frequently in combinations. Now evidence based data are gathering together in favor of their usefulness in the management of invasive fungal infections. But still, many questions are unanswered and controversies persist relating to their selection and use.

Surgical outcome of tuberculous meningitis hydrocephalus treated by endoscopic third ventriculostomy: prognostic factors and postoperative neuroimaging for functional assessment of ventriculostomy.

OBJECT: Endoscopic third ventriculostomy (ETV) is increasingly being used as an alternative treatment for post-tuberculous meningitis (TBM) hydrocephalus. The aim of this study was to affirm the role of ETV in patients with TBM hydrocephalus and also to study the usefulness of cine phase-contrast MR imaging (cine MR imaging) for functional assessment of the ETV stoma. An additional goal was to identify factors that influence the outcome of ETV, so as to define patients with TBM hydrocephalus in whom ETV is warranted. METHODS: Twenty-six patients with TBM hydrocephalus treated with ETV were evaluated clinically and with cine MR imaging postoperatively. The duration of follow-up ranged from 1 to 15 months. The authors evaluated flow void changes in the floor of the third ventricle and analyzed parameters from the preoperative data, which they then used as a basis for comparison between endoscopically successful and endoscopically unsuccessful cases. RESULTS: The overall success rate of ETV in TBM hydrocephalus was 73.1% in this case series. Cine MR imaging showed a sensitivity of 94.73% and specificity of 71.42% for the functional assessment of third ventriculostomy in these patients, with the efficacy being maintained during follow-up. The outcome of ETV showed a statistically significant correlation with the stage of illness and presence of intraoperative cisternal exudates. Although duration of symptoms and duration of preoperative antituberculous therapy (ATT) appeared to influence the outcome, their correlation with outcome was not statistically significant. CONCLUSIONS: Endoscopic third ventriculostomy should be considered as the first surgical option for CSF diversion (that is, before shunt surgery) in patients with TBM hydrocephalus. Cine MR imaging is a highly effective noninvasive tool for the postoperative functional assessment of stomata. Patients who presented with a history of longer duration and those who were administered preoperative ATT for a longer period had a better outcome of endoscopic treatment. Outcome was poorer in patients who presented with higher stages of illness and in those in whom cisternal exudates were observed intraoperatively.

Surgery without assistance in newborns and infants with hydrocephalus and neural tube defects.

Standard neurosurgical procedures for hydrocephalus and open neural tube defects in newborns and infants under 6 months of age were performed by a single neurosurgeon on his own without the help of an assistant or scrub nurse. The objective of this study was to assess the outcome of these procedures in terms of operating time, the presence of bacterial infection, and wound healing. Between 2001 and 2004, a total of 126 procedures were performed on 82 patients under 6 months of age. We observed 1 bacterial and 2 fungal infections. Two infections had already been detected at the beginning of the surgical procedure in cerebrospinal fluid (CSF) specimens obtained from children with Candida ventriculitis. The other infection occurred after leakage of CSF from a myelomeningocele 10 days after initial surgery. Our study suggests that excellent results can be achieved in standard neurosurgical procedures without assistance even in high-risk newborns and infants if resource or other constraints require such an unconventional approach.

Epidemiology and management of cryptococcal meningitis: developments and challenges.

The significance of cryptococcal infection as a cause of human disease has dramatically evolved in recent years. The objective of this study was to outline the worldwide significance of cryptococcosis and review developments in the management of cryptococcal meningitis. Cryptococcus neoformans var. grubii remains an important cause of disease, particularly in hosts with acquired immunosuppression. Cryptococcus gattii, on the other hand, infects hosts with seemingly normal immune systems and a recent dramatic outbreak in a new ecologic environment highlights the emerging clinical significance of this fungal pathogen. The introduction of new antifungal agents and the adoption of strategies for controlling elevated intracranial pressure in cryptococcal meningitis have added to our therapeutic options. However, the mortality from this infection remains unacceptably high and we are faced with the specific challenges in the management of this disease.

Do antibiotic-impregnated shunts in hydrocephalus therapy reduce the risk of infection? An observational study in 258 patients.

BACKGROUND: Shunt infection in hydrocephalus patients is a severe, even life-threatening complication. Antibiotic-impregnated shunts (AIS) have been developed in an attempt to reduce rate of shunt infection. The study was performed to analyze if AIS can diminish the rate of shunt infection. The pathogenic nature of shunt infection in patients with AIS systems and those without antibiotic impregnated shunts (non-AIS) was compared. METHODS: Over a period of 24 months in the Department of Neurosurgery at University Hospital of Tübingen shunt surgery was performed in 258 patients. In 86 patients AIS systems were implanted. Shunt catheters were commercially impregnated with clindamycin and rifampicin. Analysis of the clinical data included sex, age, classification of hydrocephalus, shunt types and risk factors for shunt infection [age (< 1 year and > 80 years), prematurely born patients, external ventricular drainage, former shunt infection, former systemic infection, disturbance of consciousness, former radiation-/chemotherapy]. Infection rates and underlying bacterial pathogens of patients with AIS were compared to patients with implanted non-AIS systems (172 patients). RESULTS: AIS and non-AIS patients did not differ in sex, etiology of hydrocephalus and the shunt type. In the AIS group 72 out of 86 patients had at least one risk factor (83.7 %), compared to 126 patients in the non-AIS group (73.3 %). There was no significant difference between the two groups (p = 0.0629; Fisher's exact test). In patients with no risk factors, only one patient with non-AIS suffered from shunt infection. In patients with one or more risk factors the rate for shunt infection was 7.14 % in patients with non-AIS and 6.94 % in patients with AIS. Former shunt infection (p = 0.0124) was related to higher risk for shunt infection. The use of AIS had therefore no significant advantage (p = 0.8611; multiple logistic regression). Significantly related to a shunt infection was the number of shunt surgeries. 190 interventions in the AIS group (2.21 interventions per patient) and 408 in the non-AIS group (2.37 interventions per patient) had been performed (p = 0.3063; Wilcoxon). There was no shunt infection in the group of patients on whom only one shunt surgery was performed. In patients with at least two shunt surgeries the infection rate was 9%. The infection rate in AIS patients was 5/52 (9.6 %) and in the non-AIS 10/114 (8.77 %), (p = 1.0; Fisher's exact test). Staphylococcus epidermidis was the most frequent pathogen for shunt infection. Fourteen out of 15 infections occurred within the first 6 months of surgery. The most frequent pathogen for shunt infection was S. epidermidis. No toxic or allergic complications were seen using the AIS shunt systems. The presented data show a remarkably low infection rate of 5.8 % in the non-AIS group compared to other studies which demonstrated a significant decrease in the infection rate by AIS. CONCLUSION: AIS did not significantly reduce shunt infection in hydrocephalus patients in the presented study. In the AIS group three patients suffered from shunt infections caused by skin ulceration or neurosurgical procedures with exposure of the cerebrospinal liquor after shunt implantation. AIS was not developed to prevent infection in such cases, therefore an advantage of AIS can not be excluded. In view of the presented data and the small number of reported studies a prospective randomized multicenter study is required.

Successful treatment of vancomycin-resistant enterococcus ventriculitis in a child

Enterococci are an uncommon cause of CNS infection. A 20 month-old boy, diagnosed with hydrocephalus with ventriculoperitoneal shunt and history of lengthy hospitalization and use of wide spectrum antibiotics, was admitted to the pediatric intensive care unit diagnosed with ventriculitis. On the 14th day of empirical antibiotic therapy (vancomycin and meropenem) the child presented fever while the CSF sample culture evidenced vancomycin-resistant Enterococcus faecium. The patient received intravenous linezolid achieving cerebrospinal fluid sterilization. Conclusion: Intravenous linezolid appears to be a safe and effective therapy for vancomycin-resistant enterococcus ventriculoperitoneal shunt infection.