The diagnosis of blocked cerebrospinal fluid shunts: a prospective study of referral to a paediatric neurosurgical unit

A prospective study was undertaken of all children referred to the Hospital for Sick Children with a provisional diagnosis of shunt blockage over a 5-month period. Fifty-two admissions were recorded, relating to 45 children, 5 of whom had multiple admissions. Only 19 of the 52 admissions led to a final diagnosis of shunt malfunction. No source of referral, whether by the child's general practitioner or from another hospital, was found to be more accurate than direct referral by the parents to the neurosurgical ward. Headache, vomiting and irritability were not significant indicators as to whether the child's shunt was actually blocked, and nor was the duration of the symptoms. Drowsiness was a significant, but not definite, indicator of shunt blockage, while pyrexia made it more likely that the patient had an alternative diagnosis. In 35 of the admissions a computed tomographic scan was performed: a normal scan, unchanged from previous scans, did not reliably exclude the diagnosis of shunt blockage. Percutaneous manometry via the reservoir of the shunt system was performed during 26 admissions: this investigation produced no false positives nor false negatives, but was equivocal in 5 cases, all of which were found at surgery to have a definite shunt blockage. The accuracy of the diagnosis of shunt blockage made prior to referral to a neurosurgical unit is discussed, together with the implications for resource use.     

Relationship between intracranial pressure and intracranial volume in craniosynostosis.

Premature fusion of cranial sutures in craniosynostosis has been thought to lead to craniostenosis, which in turn may lead to increased intracranial pressures. In 41 consecutive patients with craniosynostosis, intracranial pressure and intracranial volume were measured. Of the 41 patients, 38 (92.6%) had raised intracranial pressure but only 4 (9.7%) had a decreased skull volume. In the present study, there is no correlation between intracranial volume and intracranial pressure. This study confirms that the measurement of intracranial volume, a non invasive procedure, cannot be used to assess intracranial pressure and to avoid an invasive procedure.     

Microfluidic Preparation of Liposomes to Determine Particle Size Influence on Cellular Uptake Mechanisms

Purpose

This study investigates the cellular uptake and trafficking of liposomes in Caco-2 cells, using vesicles with distinct average diameters ranging from 40.6 nm to 276.6 nm. Liposomes were prepared by microfluidic hydrodynamic flow focusing, producing nearly-monodisperse populations and enabling size-dependent uptake to be effectively evaluated.

Methods

Populations of PEG-conjugated liposomes of various distinct sizes were prepared in a disposable microfluidic device using a simple continuous-flow microfluidic technique. Liposome cellular uptake was investigated using flow cytometry and confocal microscopy.

Results

Liposome uptake by Caco-2 cells was observed to be strongly size-dependent for liposomes with mean diameters ranging from 40.6 nm to 276.6 nm. When testing these liposomes against endocytosis inhibitors, cellular uptake of the largest (97.8 nm and 162.1 nm in diameter) liposomes were predominantly subjected to clathrin-dependent uptake mechanisms, the medium-sized (72.3 nm in diameter) liposomes seemed to be influenced by all investigated pathways and the smallest liposomes (40.6 nm in diameter) primarily followed a dynamin-dependent pathway. In addition, the 40.6 nm, 72.3 nm, and 162.1 nm diameter liposomes showed slightly decreased accumulation within endosomes after 1 h compared to liposomes which were 97.8 nm in diameter. Conversely, liposome co-localization with lysosomes was consistent for liposomes ranging from 40.6 nm to 97.8 nm in diameter.

Conclusions

The continuous-flow synthesis of nearly-monodisperse populations of liposomes of distinct size via a microfluidic hydrodynamic flow focusing technique enabled unique in vitro studies in which specific effects of particle size on cellular uptake were elucidated. The results of this study highlight the significant influence of liposome size on cellular uptake mechanisms and may be further exploited for increasing specificity, improving efficacy, and reducing toxicity of liposomal drug delivery systems.     

Subdural intracranial pressure monitoring in craniosynostosis: its role in surgical management

In the management of craniosynostosis subdural intracranial pressure (ICP) monitoring has proved a useful and safe means of identifying those children with raised ICP who are at risk from its long-term sequelae and who would benefit from early surgical intervention. Overnight subdural ICP recordings have been obtained in 136 unoperated cases of craniosynostosis. Fifteen patients were studied both before and after cranial vault remodelling procedures. ICP was raised (>15 mmHg) in 35%, borderline (10–15 mmHg) in 27% and normal (<10 mmHg) in 27% of cases. Raised ICP was present in 28/53 of the syndromic craniofacial dysostosis cases and in 20/83 non-syndromic craniosynostosis cases investigated (P<0.001). Raised mean ICP and periodic plateaux of sustained ICP during sleep were particularly associated with the syndromic cases. Of the 15 patients studied following cranial vault surgery, 9 showed a reduction in ICP, 3 were unchanged and 3 had higher ICP postoperatively. The results of ICP monitoring can contribute significantly to formulating a rational and staged surgical management plan incorporating the need to normalise ICP and correct the frequently severe functional and cosmetic consequences of these disorders.     

Computed tomography in Alexander's disease

Summary A case of biopsy proven Alexander's disease is described with extensive low density lesions in both frontal lobes, which in our experience, and on survey of the literature have not been described previously.