Central nervous system infection after Onyx embolisation of arterio-venous malformations in two paediatric patients.

BACKGROUND: Increasingly, Onyx is used for endovascular embolization of aneurysms and arterio-venous malformations. Although reports in the literature on the use of Onyx are favourable, there have been so far no reports on the central nervous system (CNS) infection rate after embolisation with Onyx and no recommendations as to the management of these infections. CASE REPORTS: We present two cases of paediatric patients who acquired CNS infection with Pseudomonas aeruginosa after Onyx embolisation of AVMs and describe their subsequent management. CONCLUSIONS: Presence of established infection after Onyx embolisation should be dealt with by removal of infected material, administration of appropriate antibiotic therapy and supportive treatment.

Serial PCR genetic load determination in the surgical management of pneumococcal intracranial sepsis.

PURPOSE: Aspirated intracranial fluid, in the surgical management of intracranial sepsis, may not culture an organism due to the previous administration of antibiotics. We have sought to utilise polymerase chain reaction (PCR) to determine the cause of culture-negative sepsis and in monitoring response to therapy. METHODS: This was a retrospective review of five cases of Streptococcus pneumoniae intracranial sepsis. Samples were analysed using real-time quantitative PCR targeting the pneumococcal lytA gene and the number of genome copies per microlitre of sample determined. RESULTS: Streptococcus pneumoniae sepsis was diagnosed by PCR in five culture-negative cases comprising: ventriculitis (×3), subdural empyema and meningitis. Serial serum inflammatory markers (CRP and WBC) and number of genome copies were graphically plotted over the duration of inpatient stay for cases requiring surgical drainage of recurrent collections or external ventricular drainage. A correlation was demonstrated between change in bacterial genomic load and serum inflammatory markers, reflecting similar changes in clinical state. CONCLUSIONS: This is the first report of the use of serial quantitative PCR in monitoring the course of intracranial sepsis secondary to S. pneumoniae. Further work is required to determine the precise relationship between serum inflammatory markers, clinical state and bacterial load: do changes in one precede the other? Furthermore, a threshold value for number of genome copies in cerebrospinal fluid/aspirate samples has yet to be defined.

Premature mortality in refractory partial epilepsy: does surgical treatment make a difference?

BACKGROUND: Epilepsy carries an increased risk of premature death. For some people with intractable focal epilepsy, surgery offers hope for a seizure-free life. The authors aimed to see whether epilepsy surgery influenced mortality in people with intractable epilepsy. METHODS: The authors audited survival status in two cohorts (those who had surgery and those who had presurgical assessment but did not have surgery). RESULTS: There were 40 known deaths in the non-surgical group (3365 person years of follow-up) and 19 in the surgical group (3905 person-years of follow-up). Non-operated patients were 2.4 times (95% CI 1.4 to 4.2) as likely to die as those who had surgery. They were 4.5 times (95% CI 1.9 to 10.9) as likely to die a probable epilepsy-related death. In the surgical group, those with ongoing seizures 1 year after surgery were 4.0 (95% CI 1.2 to 13.7) times as likely to die as those who were seizure-free or who had only simple partial seizures. Time-dependent Cox analysis showed that the yearly outcome group did not significantly affect mortality (HR 1.3, 95% CI 0.9 to 1.8). CONCLUSION: Successful epilepsy surgery was associated with a reduced risk of premature mortality, compared with those with refractory focal epilepsy who did not have surgical treatment. To some extent, the reduced mortality is likely to be conferred by inducing freedom from seizures. It is not certain whether better survival is attributable only to surgery, as treatment decisions were not randomised, and there may be inherent differences between the groups.

Astrocytoma derived short-term cell cultures retain molecular signatures characteristic of the tumour in situ.

The heterogeneity of tumours and uncertainties surrounding derived short-term cell cultures and established cell lines fundamentally challenge the research and understanding of tumour growth and development. When tumour cells are cultured, changes are inevitably induced due to the artificial growth conditions. Several recent studies have questioned how representative established cell lines or derived short-term cell cultures are of the tumour in situ. We have characterised gene expression changes induced by short-term culture in astrocytoma in order to determine whether derived short-term cell cultures are representative of the tumour in situ. In comparison to the majority of studies, paired biopsies and derived short-term cultures were investigated to reduce the effects of long-term culture and inter-tumour variability when comparing biopsies and derived cultures from tumours with the same histology from different individuals. We have used the Affymetrix GeneChip U133A to generate gene expression profiles of 6 paediatric pilocytic astrocytoma (PA) biopsies and derived short-term cell cultures and 3 adult glioblastoma multiforme (GBM) biopsies and derived short-term cultures. Significant differential gene expression is induced by short-term culture. However, when the biopsy and derived short-term cell culture samples were grouped according to tumour type (PA and GBM) a molecular signature of 608 genes showed significant differential expression between the groups. This gene cohort can distinguish PA and GBM tumours, regardless of the sample source, suggesting that astrocytoma derived short-term cultures do retain key aspects of the global tumour expression profile and are representative of the tumour in situ. Furthermore, these genes are involved in pathways and functions characteristic of adult GBM including VEGF signalling, hypoxia and TP53 signalling.

Disproportion in the distribution of gray and white matter: neuropsychological correlates.

OBJECTIVE: To examine the relationship between measures of disproportion in the regional distribution of gray and white matter and preoperative neuropsychological function in temporal lobe epilepsy patients with proved hippocampal sclerosis (HS). BACKGROUND: Subtle cerebral structural disruption, not evident on routine inspection of high-resolution MRI, is associated with poor surgical outcome in patients with histologically proved HS. Preoperative global memory dysfunction is also associated with poor postoperative seizure control. The authors hypothesize that patients with HS and abnormal regional distributions of gray and white matter would show more diffuse neuropsychological deficits preoperatively than patients with isolated HS alone. METHODS: A total of 28 adults with lateralized temporal lobe epilepsy and hippocampal volume loss measured on MRI were assessed preoperatively on neuropsychological tests of general intellect and the learning and recall of both verbal and nonverbal material. Quantitative MRI analysis of the regional distribution of gray and white matter was performed. Chi-square analyses were used to examine the relation between the presence or absence of cerebral abnormalities and preoperative performance on the neuropsychological tests. RESULTS: A total of 15 of 28 patients had extrahippocampal abnormalities on quantitative MRI analysis. Thirteen patients had global memory impairment. Bilateral memory deficits were significantly associated with both the presence of cerebral abnormalities (p < 0.02) and poor postoperative seizure control (p < 0.05). CONCLUSIONS: Disproportion in the regional distribution of gray and white matter in patients with HS may form the structural basis of global memory disturbance in a distinct group of patients with temporal lobe epilepsy.

Surgical treatment of patients with single and dual pathology: relevance of lesion and of hippocampal atrophy to seizure outcome.

Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engel's class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p < 0.007). All three patients with dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p < 0.05), although 4 of them showed significant improvement (Engel's class II). We conclude that the outcome in patients with single epileptogenic lesions is usually dependent upon the completeness of lesion resection. In patients with dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus.

Chemosensitivity in childhood brain tumours in vitro: evidence of differential sensitivity to lomustine (CCNU) and vincristine.

The aim of this study was to examine the range of sensitivity of a panel of short-term cultures derived from different types of malignant childhood brain tumours including medulloblastoma, ependymoma and glioblastoma multiforme to three cytotoxic drugs, lomustine (CCNU), vincristine (VCR) and procarbazine (PCB). Sensitivity was assessed using a modification of the dimethylthiazolyl-2,5-diphenyl tetrazolium bromide (MTT) assay. Short-term cell lines derived from ependymomas were considerably more resistant to VCR than other types of childhood brain tumours, while cultures derived from supratentorial primitive neuroectodermal tumour (PNET) displayed marked sensitivity to both lomustine and VCR. Cultures from ependymomas, medulloblastoma and astrocytic gliomas had similar sensitivity to lomustine and PCB as cultures derived from adult malignant astrocytoma.

Central benzodiazepine receptor autoradiography in hippocampal sclerosis.

1. The gamma-aminobutyric acid (GABA)A/central benzodiazepine receptor (cBZR) complex is a major inhibitory receptor in the vertebrate CNS. Binding of [11C]-flumazenil to this complex in vivo is reduced in hippocampal sclerosis (HS). It has been uncertain whether reduced cBZR binding is entirely due to neuronal loss in HS. 2. The objective of this study was to characterize abnormalities of the cBZR in HS with a correlative autoradiographic and quantitative neuropathological study. 3. Saturation autoradiographic studies were performed with [3H]-flumazenil to investigate relationships between neuronal density and receptor availability (Bmax) and affinity (Kd) in HS. Hippocampal tissue was obtained at surgery from 8 patients with intractable temporal lobe epilepsy (TLE) due to HS and autopsies of 6 neurologically normal controls. Neuronal densities were obtained by means of a 3-D counting method. 4. Bmax values for [3H]-flumazenil binding in the subiculum, CA1, CA2, CA3, hilus and dentate gyrus were all found to be significantly reduced in HS compared with controls and significant increases in affinity were observed in the subiculum, hilus and dentate gyrus. In HS, cBZR density in the CA1 region was significantly reduced (P < 0.05) to a greater extent than could be attributable to neurone loss. In other regions, Bmax was reduced in parallel with neuronal density. 5. In HS, there is a loss of cBZR in CA1 over and above loss of neurones. This finding and increases in affinity for flumazenil in subiculum, hilus and dentate gyrus imply a functional abnormality of the GABAA/cBZR complex that may have a role in the pathophysiology of epileptogenicity in HS.

Epileptic nystagmus in infancy.

Epileptic nystagmus (EN) is a rare form of nystagmus that occurs only during epileptic seizures. We report an infantile case in which EN was first noted at 10 days of age. Electronystagmography showed a right-beating nystagmus with predominantly linear slow phases that traversed the midline. Neuro-imaging revealed dysplasia of the left middle temporal gyrus extending posteriorly into the parieto-occipital cortex. The right hemisphere and subcortical structures appeared normal. Perfusion studies demonstrated interictal hypoperfusion with ictal hyperperfusion in the left temporal lobe. Electrocorticography demonstrated spiking over the left temporal-parieto-occipital region. Following extensive surgical resection of this area and weaning of anti-convulsants, the child has remained seizure-free without nystagmus. This case demonstrates the cortical origin of EN, and shows that infant cortex has functioning efferent connections to brainstem oculomotor centres from 10 days of age.

The effect of protein and blood cells on the flow-pressure characteristics of shunts.

It has long been assumed that a high cerebrospinal fluid protein concentration adversely affects the performance of shunts. There is little experimental evidence to support this viewpoint, however, and the few reports that have been published can be criticized for poor experimental design or presentation of results. A flow-dependent shunt perfusion model was constructed. PS Medical Flow Control valves (PS Medical Corporation, Goleta, CA) and Cordis-Hakim valves (Cordis Corporates, Miami, FL) were perfused with saline-plasma solutions in concentrations from 0 to 9 g/L of protein. Blood suspensions in dilutions from 0.25 to 1% were also studied. The opening and closing pressures of the valves were measured with a simple manometer, and the physical properties of the solutions were studied. The results indicated that the valves performed within the ranges specified by their manufacturers, even with markedly increased protein concentrations in the perfusate. Furthermore, the valve opening and closing pressures were lower with the protein-containing solutions than with the control solutions. Thus, the protein did not impair shunt function and we conclude that shunts can be inserted into patients who have elevated cerebrospinal fluid protein contents. However, blood cells did adversely affect performance and, therefore, patients with hemorrhagic cerebrospinal fluid should not receive shunts.

Use of intracranial pressure monitoring in the management of childhood hydrocephalus and shunt-related problems.

Although the clinical and radiological diagnosis of hydrocephalus in children is usually straightforward, there exists a minority of patients in whom the decision to shunt can be extremely difficult. Similarly, although the diagnosis of shunt malfunction usually presents little difficulty in the context of an acute blockage, a child can present with a confusing and unpredictable constellation of symptoms that might be caused by conditions separate from shunt malfunction. Continuous intraparenchymal intracranial pressure (ICP) monitoring was used to assess 41 patients with hydrocephalus, either as part of the initial diagnostic evaluation of ventriculomegaly (18 patients) or in the assessment of presumed shunt malfunction (23 patients). In 9 of 18 patients with ventriculomegaly, the ICP was within normal limits and surgical insertion of shunts was avoided. Of the 23 patients being assessed for shunt malfunction, the change in ICP profile indicated a siphoning or overdrainage process in 13. In no patient was there significant attendant morbidity, and the process was well tolerated and simple to perform. Clinical and radiological criteria alone can afford insufficient information in the initial evaluation and the subsequent management of the child with hydrocephalus. ICP monitoring provides a safe means of investigating such patients and provides valuable information upon which to base surgical management.

The effectiveness of papilledema as an indicator of raised intracranial pressure in children with craniosynostosis.

Craniosynostosis management partially depends on the detection and treatment of elevated intracranial pressure (ICP). Examination for papilledema is considered to be the most reliable screening method for identifying raised ICP, but its effectiveness has not been defined. One hundred and twenty-two children with craniosynostosis who underwent funduscopic examinations and then Camino ICP monitoring were studied. All eye examinations were performed by an ophthalmologist after pharmacological pupillary dilation. Fifteen patients (12%) had papilledema. Subsequent ICP monitoring showed that the median ICP was 12.7 mm Hg, with 41 patients (34%) having elevated ICPs (> 15 mm Hg). Those with papilledema had higher ICPs (17.5 +/- 3.2 versus 12.7 +/- 5.5 mm Hg), were older (5.9 +/- 4.7 versus 1.9 +/- 2.6 years), and were more likely to have craniofacial syndromes (73 versus 41%) than those without papilledema (P < 0.05). Patients with both elevated ICPs and papilledema were older (5.9 +/- 4.7 versus 1.6 +/- 1.4 years) and more likely to have multiple-suture synostosis (92 versus 61%) than those with elevated ICPs and no papilledema (P < 0.05). The presence of papilledema was a specific (98%) indicator of raised ICP, but its sensitivity was age-dependent. It was 100% sensitive in children older than 8 years, but it indicated elevated ICP in only 22% of younger patients. These results suggest that ICP monitoring to document elevated ICP is unnecessary in children older than 8 years who have detailed ophthalmological examinations. In the younger child, the presence of papilledema reliably indicates elevated ICP but its absence does not rule out elevated ICP; formal ICP measurement has a greater role in detecting elevated ICP in these patients.

The beaten copper cranium: a correlation between intracranial pressure, cranial radiographs, and computed tomographic scans in children with craniosynostosis.

OBJECTIVE: The beaten copper appearance of the cranium, as well as other cranial radiographic and computed tomographic findings in children with craniosynostosis, is often interpreted by clinicians as evidence of elevated intracranial pressure (ICP). However, a correlation between radiological findings and ICP measurements has not been previously demonstrated, and their usefulness in detecting elevated ICP has not been defined. METHODS: To address those issues, 123 children with craniosynostosis who had cranial radiographs and ICP monitoring were studied. To assess the specificity of certain radiological findings to patients with craniosynostosis, cranial radiographs of patients with craniosynostosis were compared to those of age- and sex-matched controls. In patients with craniosynostosis, findings on cranial radiographs were compared to computed tomographic scans of the brain. Radiographic findings were then correlated with ICP measurements obtained while the patient was sleeping, which was measured using a Camino fiberoptic ICP monitor (Camino Laboratories, San Diego, CA). All radiographs were independently analyzed by two radiologists who were blinded to clinical and ICP data. RESULTS: A diffuse beaten copper pattern, erosion of the dorsum sellar, and suture diastasis were seen more commonly in patients with craniosynostosis than in controls (P < 0.05), but the presence of the beaten copper pattern was no more common in children with craniosynostosis. ICP was greater when a diffuse beaten copper pattern, dorsum sellar erosion, suture diastasis, or narrowing of basal cisterns was present (P < 0.05). CONCLUSION: Although this study demonstrates that some cranial radiographic and computed tomographic findings do correlate with elevated ICP, the sensitivity of radiological methods for detecting elevated ICP is universally low and they are not recommended to screen for elevated ICP in children with craniosynostosis.

The significance of bilateral EEG abnormalities before and after hemispherectomy in children with unilateral major hemisphere lesions.

The rate of seizure relief following hemispherectomy varies between 50 and more than 80%. There has been particular debate concerning the significance of bilateral electroencephalography (EEG) abnormalities in influencing prognosis. This study was set out to determine the frequency of bilateral EEG abnormalities and their relationship to underlying pathology and outcome. We investigated 28 children with unilateral hemisphere lesions, who underwent hemispherectomy. Interictal and ictal EEGs before and after hemispherectomy were reviewed. Post-operative outcome with respect to seizures was noted. Bilateral EEG abnormalities were seen in 75%, but were more common in children with malformations of cortical development than in patients with acquired cerebral lesions, and were found more often in interictal than in ictal records. Post-operative EEG abnormalities were variable and did not consistently predict outcome. Short-term outcome was similar, irrespective of aetiology. With longer term follow-up, only 47% of children with developmental abnormalities were still seizure-free in contrast to 77% of children with acquired abnormalities. Although the incidence of bilateral EEG abnormalities in patients with major unilateral hemisphere lesions is high, these findings alone should not preclude further consideration for hemispherectomy. Our findings emphasise that the aetiology of the lesion plays a major role in determining outcome.

Accurate placement of the atrial catheter in ventriculoatrial shunts. Technical note.

A combined radiological and surgical technique that permits identification of appropriate recipient vessels and accurate placement of the atrial catheter in ventriculoatrial shunts is described. The procedure uses readily available radiological skills and reduces operation time and morbidity related to malpositioning of the distal catheter.

Lessons from a case of kleeblattschädel. Case report.

The authors describe the clinical, radiological, and postmortem findings of a case of cloverleaf skull syndrome. The presence of hindbrain herniation, abnormal cervical segmentation, and atlantoaxial subluxation illustrate the anatomical complexity of the skull base and the craniocervical junction that may coexist in this condition. Unavoidable division of occipital emissary veins during elevation of the skin flap at the time of vault remodeling surgery led to an acute and, ultimately, fatal rise in intracranial pressure. Postmortem examination and review of magnetic resonance imaging revealed an anomalous pattern of venous drainage of the intracranial structures that appeared to have developed in response to venous obstruction, secondary to intraosseous venous sinuses and stenosis of the jugular foramina. The relationship between venous hypertension, hindbrain herniation, and hydrocephalus in this situation is reviewed, and the implications for evaluation and management of this vexing disorder are discussed.

Medulloblastoma: is the 5-year survival rate improving? A review of 80 cases from a single institution.

A series of 80 cases of medulloblastomas in children undergoing operation and postoperatively followed between 1980 and 1990 at Great Ormond Street Hospital for Children (GOSH) has been reviewed and compared to an earlier series reported from the same institution by McIntosh. The overall 5-year survival rate for the present series was 50%, although three patients died after surviving 5 years. The operative mortality rate was 5%. Survival analysis revealed that the presence or absence of spinal metastases and the necessity for some form of cerebrospinal fluid diversion within 30 days of the operation independently significantly affected survival in this series. Those patients with no spinal metastasis and total tumor removal had a 5-year survival rate of 73%, making this the most favorable subgroup in the series. Patient age and gender, duration of symptoms, Chang T stages, tumor volume, extent of resection, and postoperative chemotherapy were not significant variables. Although these results are better than those reported in the earlier GOSH series, they are not significantly different from the results of the second 5-year cohort of patients described in that article. Radiotherapy remains the greatest advance in treatment, although it is hoped that further improvement will result from the various chemotherapy protocols now being studied and from increasing knowledge of the biological behavior of these tumors.

Surveillance neuroimaging in childhood intracranial ependymoma: how effective, how often, and for how long?

OBJECT: The authors examined images obtained in 52 children with intracranial ependymomas to determine risk factors for tumor recurrence and to assess the impact of surveillance imaging on patient outcome. METHODS: Data obtained in all children with intracranial ependymomas were prospectively entered into a database from January 1987 to June 2000. The imaging and clinical details in all patients were reviewed. Fifty-two children with histologically proven intracranial ependymomas were treated at the authors' institution; recurrences developed in 28 (54%) of them, with a median time from surgery to first recurrence of 14.5 months (range 3-65 months). Of these tumor recurrences, 43% were asymptomatic and were noted on surveillance imaging. Seventeen children died, all of whom had recurrences. Incomplete excision of the primary tumor was significantly associated with reduced time to recurrence (p = 0.0144) and time to death (p = 0.0472). The age of the patient, location of the primary tumor, histological findings, and the presence or absence of spinal metastases on preoperative imaging were not significantly associated with outcome. The risk of death at any given time was 12-fold greater in patients in whom a recurrence was identified due to symptoms rather than on surveillance images (p = 0.016). CONCLUSIONS: Recurrent childhood ependymoma has a poor prognosis. The extent of the initial local tumor resection is the factor most closely associated with outcome. Surveillance imaging reveals a substantial number of asymptomatic recurrences, and survival appears to be improved in these patients compared with those identified by symptoms. The improvement in survival is thought to be greater than that expected just from earlier diagnosis.

Postimaging brain distortion: magnitude, correlates, and impact on neuronavigation.

OBJECT: This prospective study was conducted to quantify brain shifts during open cranial surgery, to determine correlations between these shifts and image characteristics, and to assess the impact of postimaging brain distortion on neuronavigation. METHODS: During 48 operations, movements of the cortex on opening, the deep tumor margin, and the cortex at completion were measured relative to the preoperative image position with the aid of an image-guidance system. Bone surface offset was used to assess system accuracy and correct for registration errors. Preoperative images were examined for the presence of edema and to determine tumor volume, midline shift, and depth of the lesion below the skin surface. Results were analyzed for all cases together and separately for four tumor groups: 13 meningiomas, 18 gliomas, 11 nonglial intraaxial lesions, and six skull base lesions. For all 48 cases the mean shift of the cortex after dural opening was 4.6 mm, shift of the deep tumor margin was 5.1 mm, and shift of the cortex at completion was 6.7 mm. Each tumor group displayed unique patterns of shift, with significantly greater shift at depth in meningiomas than gliomas (p = 0.007) and significantly less shift in skull base cases than other groups (p = 0.003). Whereas the preoperative image characteristics correlating with shift of the cortex on opening were the presence of edema and depth of the tumor below skin surface, predictors of shift at depth were the presence of edema, the lesion volume, midline shift, and magnitude of shift of the cortex on opening. CONCLUSIONS: This study quantified intraoperative brain distortion, determined the different behavior of tumors in four pathological groups, and identified preoperative predictors of shift with which the reliability of neuronavigation may be estimated.

What to consider when conducting a cost-effectiveness analysis in a clinical setting.

More data are needed providing strong evidence that nutrition services are cost-effective. Economic evaluations, such as cost-effectiveness analyses, are excellent practice-based research projects. We conducted a cost-effectiveness analysis in a clinical setting to compare the cost-effectiveness of lipid-lowering medications plus diet therapy (medication + diet) with diet therapy alone (diet alone) for treating patients with hypercholesterolemia. Twenty-five adults with hypercholesterolemia (13 receiving medication + diet, 12 receiving diet alone) either participated in an 8-week, home-based, step 1 intervention or were counseled about diet and lifestyle by their care provider. Diet, cost, and laboratory data were collected at baseline, at 9 months, and at 19 months after participation in the intervention (follow-up). Cost per unit change in outcome was evaluated for each group. The diet-alone group made only small changes in dietary intake, changes that were smaller in magnitude than those made by the medication + diet group. Nevertheless, at 9 months, costs per unit change in total serum cholesterol level and low-density lipoprotein cholesterol (LDL-C) level were approximately $24 and $83 less, respectively, for the diet-alone group. At follow-up, however, the cost per unit change in LDL-C level was approximately $17 less for the medication + diet group, which can be explained by the medication + diet group's greater decrease in LDL-C level. The following elements should be considered when conducting a cost-effectiveness analysis of medical nutrition therapy: effectiveness of the nutrition intervention, adequate sample size, confounding variables, compliance with diet and drug therapy, direct and indirect costs of care, and follow-up evaluation.