Intraventricular haemorrhage and posthaemorrhagic ventricular dilatation: moving beyond CSF diversion

Advances in medical care have led to more premature babies surviving the neonatal period. In these babies, germinal matrix haemorrhage (GMH), intraventricular haemorrhage (IVH) and posthaemorrhagic ventricular dilatation (PHVD) are the most important determinants of long-term cognitive and developmental outcomes. In this review, we discuss current neurosurgical management of IVH and PHVD, including the importance of early diagnosis of PHVD, thresholds for intervention, options for early management through the use of temporising measures and subsequent definitive CSF diversion. We also discuss treatment options for the evolving paradigm to manage intraventricular blood and its breakdown products. We review the evidence for techniques such as drainage, irrigation, fibrinolytic therapy (DRIFT) and neuroendoscopic lavage in the context of optimising cognitive, neurodevelopmental and quality of life outcomes in these premature infants

Neurocognitive dysfunction after treatment for pediatric brain tumors:Subtype-specific findings and proposal for brain network-informed evaluations

The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment. As the lesion itself, as well as each treatment, can cause specific neural damage, the long-term neurocognitive outcomes are highly complex and challenging to assess. The number of neurocognitive studies in this population grows exponentially worldwide, motivating modern neuroscience to provide guidance in follow-up before, during and after treatment. In this review, we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor types. Based on this information, we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials

Towards the Discrimination of Primary and Secondary Headache: An Intelligent Systems Approach

We consider the use of intelligent systems to address the long-standing medical problem of diagnostic differentiation between harmful (secondary) and benign (primary) headache conditions. In secondary headaches, the condition is caused by an underlying pathology, in contrast to primary headaches where the production of pain represents the sole constituent of the disorder. Conventional diagnostic paradigms carry an unacceptable risk of misdiagnosis, leaving patients open to potentially catastrophic consequences. Intelligent systems approaches, grounded in artificial intelligence, are adopted in this study as a potential means to unite contributions from multiple settings, including medicine, the life sciences, pervasive computation, sensor technologies, and autonomous intelligent agency, in the fight against headache uncertainty. In this paper, we therefore present the first steps in our research towards a data intensive, unified approach to headache dichotomisation. We begin by presenting a background to headache and its classification, followed by analysis of the space of confounding symptoms, in addition to the problem of primary and secondary condition discrimination. Finally, we proceed to report results of a preliminary case study, in which the epileptic seizure is considered as a manifestation of a headache generating neuropathology. It was found that our classification approach, based on supervised machine learning, represents a promising direction, with a best area under curve test outcome of 0.915. We conclude that intelligent systems, in conjunction with biosignals, could be suitable for classification of a more general set of pathologies, while facilitating the medicalisation of arbitrary settings

The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial): study protocol

BACKGROUND: Insertion of a ventriculoperitoneal shunt (VPS) for the treatment of hydrocephalus is one of the most common neurosurgical procedures in the UK, but failures caused by infection occur in approximately 8% of primary cases. VPS infection is associated with considerable morbidity and mortality and its management results in substantial cost to the health service. Antibiotic-impregnated (rifampicin and clindamycin) and silver-impregnated VPS have been developed to reduce infection rates. Whilst there is some evidence showing that such devices may lead to a reduction in VPS infection, there are no randomised controlled trials (RCTs) to support their routine use. METHODS/DESIGN: Overall, 1,200 patients will be recruited from 17 regional neurosurgical units in the UK and Ireland. Patients of any age undergoing insertion of their first VPS are eligible. Patients with previous indwelling VPS, active and on-going cerebrospinal fluid (CSF) or peritoneal infection, multiloculated hydrocephalus requiring multiple VPS or neuroendoscopy, and ventriculoatrial or ventriculopleural shunt planned will be excluded. Patients will be randomised 1:1:1 to either standard silicone (comparator), antibiotic-impregnated, or silver-impregnated VPS. The primary outcome measure is time to VPS infection. Secondary outcome measures include time to VPS failure of any cause, reason for VPS failure (infection, mechanical failure, or patient failure), types of bacterial VPS infection (organism type and antibiotic resistance), and incremental cost per VPS failure averted. DISCUSSION: The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial) is the first multi-centre RCT designed to determine whether antibiotic or silver-impregnated VPS reduce early shunt infection compared to standard silicone VPS. The results of this study will be used to inform current neurosurgical practice and may potentially benefit patients undergoing shunt surgery in the future. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN49474281

Patients Attitude to Technology: A Way to Improve Hydrocephalus Management and Follow up Using Smartphone Intelligent Application

Smartphone applications (”apps”) have become ubiquitous with the advent of smartphones and tablets in recent years.Increasingly the utility of these apps is being explored in healthcare delivery. Hydrocephalus is a condition that is usually followed by a neurosurgeon for the patient’s life. We explore patient acceptability of a mobile app as an adjunct to outpatient follow-up of patients with hydrocephalus. A questionnaire was circulated amongst patients with hydrocephalus (adults and children). Patients were asked questions about their hydrocephalus; expectations for outpatient follow up, whether they have smartphone/tablet/internet access and whether they would be interested in a mobile app for their long term hydrocephalus follow up. 191 patients completed questionnaires, 98 respondents were adults (mean age 46.1) and 93 were children less than 18 years old (mean age 8). Overall 36.1% of patients did not know the cause of their hydrocephalus. 96.7% have a shunt. 76.5% of adults and 80.6% of children had 1-4 shunt surgeries, 14.3% of adults and 11.8% of children had 5-9 shunt surgeries, 3.1% of adults and 5.4% of children had 10-14 shunt surgeries. 71.7% of patients expect to be followedup routinely in clinic for life. All children had smartphones or tablets, compared to 86.7% of adults. Children were more interested in a hydrocephalus app, 84.9% saying yes, compared to 71.4% of adults. Adults who were not interested in the app did not have a smartphone or tablet. Hydrocephalus management is a lifelong task and innovations in technology for engaging patients in its management are vital. The majority of patients are interested in mobile apps for outpatient management of hydrocephalus. We will follow this up with a feasibility study of a custom designed hydrocephalus app

RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration.

In the healthy adult brain synapses are continuously remodelled through a process of elimination and formation known as structural plasticity. Reduction in synapse number is a consistent early feature of neurodegenerative diseases, suggesting deficient compensatory mechanisms. Although much is known about toxic processes leading to synaptic dysfunction and loss in these disorders, how synaptic regeneration is affected is unknown. In hibernating mammals, cooling induces loss of synaptic contacts, which are reformed on rewarming, a form of structural plasticity. We have found that similar changes occur in artificially cooled laboratory rodents. Cooling and hibernation also induce a number of cold-shock proteins in the brain, including the RNA binding protein, RBM3 (ref. 6). The relationship of such proteins to structural plasticity is unknown. Here we show that synapse regeneration is impaired in mouse models of neurodegenerative disease, in association with the failure to induce RBM3. In both prion-infected and 5XFAD (Alzheimer-type) mice, the capacity to regenerate synapses after cooling declined in parallel with the loss of induction of RBM3. Enhanced expression of RBM3 in the hippocampus prevented this deficit and restored the capacity for synapse reassembly after cooling. RBM3 overexpression, achieved either by boosting endogenous levels through hypothermia before the loss of the RBM3 response or by lentiviral delivery, resulted in sustained synaptic protection in 5XFAD mice and throughout the course of prion disease, preventing behavioural deficits and neuronal loss and significantly prolonging survival. In contrast, knockdown of RBM3 exacerbated synapse loss in both models and accelerated disease and prevented the neuroprotective effects of cooling. Thus, deficient synapse regeneration, mediated at least in part by failure of the RBM3 stress response, contributes to synapse loss throughout the course of neurodegenerative disease. The data support enhancing cold-shock pathways as potential protective therapies in neurodegenerative disorders