Several molecular subtypes of sporadic Creutzfeldt–Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt–Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt–Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt–Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease. Patients with sporadic Creutzfeldt–Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as ‘suspected sporadic Creutzfeldt–Jakob disease’ but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt–Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt–Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic resonance imaging was positive in 83% of cases. In all definite cases, the amended criteria would cover the vast majority of suspected cases, being positive in 98%. Cerebral cortical signal increase and high signal in caudate nucleus and putamen on fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging are useful in the diagnosis of sporadic Creutzfeldt–Jakob disease. We propose an amendment to the clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease to include findings from magnetic resonance imaging scans.
Cortical signal increase and hyperintensities in the basal ganglia and thalamus are detected by MRI across all molecular sporadic Creutzfeldt-Jakob disease subtypes. Our findings argue that characteristic MRI lesion patterns may occur for each molecular subtype.
Study design: Review. Objectives: To highlight the value of investigating the effects of putative therapeutic interventions in clinical spinal cord injury (SCI) in domestic dogs. Setting: England, UK. Methods: Many experimental interventions in laboratory rodents have been shown to ameliorate the functional deficits caused by SCI; the challenge now is to determine whether they can be translated into useful clinical techniques. Important differences between clinical SCI in human patients and that in laboratory rodents are in the size of the spinal cord and heterogeneity of injury severity. A further key issue is whether the statistical difference in outcome in the laboratory will translate into a useful difference in clinical outcome. Here, we stress the value of investigating the effects of putative therapies in clinical SCI in domestic dogs. The causes of injury, ability to categorise the severity and methods available to measure outcome are very similar between canine and human patients. Furthermore, postmortem tissue more rapidly becomes available from dogs because of their short lifespan than from human patients. Results: The role that investigation of canine SCI might play is illustrated by our preliminary trials on intraspinal transplantation of olfactory glial cells for severe SCI. Conclusions: This canine translational model provides a means of 'filtering' putative treatments before human application.
Microdialysis monitoring of cerebral metabolism is now performed in several neuro-intensive care units. Conventional microdialysis utilizes CMA70 catheters with 20 kDa molecular weight cut-off membranes enabling the measurement of small molecules such as glucose, lactate, pyruvate and glutamate. The CMA71 100 kDa molecular weight cut-off microdialysis catheter has recently been introduced to allow detection of larger molecules such as cytokines. The objective of this study was to perform in vitro and in vivo testing of the CMA71 microdialysis catheter, comparing its performance with the CMA70. In vitro comparison studies of three of each catheter using reference analyte solutions, demonstrated equivalent recovery for glucose, lactate, pyruvate and glutamate (range 94-97% for CMA70 and 88-103% for CMA71). In vivo comparison involved intracranial placement of paired CMA70 and CMA71 catheters (through the same cranial access device) in six patients with severe traumatic brain injury. Both catheters were perfused with CNS Perfusion Fluid without dextran at 0.3 microl min-1 with hourly sampling and bedside analysis on a CMA600 microdialysis analyser. The two catheters yielded equivalent results for glucose, lactate, pyruvate, glutamate and lactate/pyruvate ratio. CMA71 microdialysis catheters can, therefore, be used for routine clinical monitoring of extracellular substances, as well as for their intended research role of larger molecular weight protein sampling.
Epilepsy is a common neurological condition in dogs and cats. Although an increased likelihood of significant brain lesions with age has been identified in neurologically normal dogs with epileptic seizures, the underlying aetiology of epileptic seizures in cats that present with normal physical and neurological examinations remains unknown. In this cross‐sectional study, the authors examined MRI findings in a large population of cats with a normal interictal physical and neurological examination. They hypothesised that age would have an impact on the prevalence of detectable lesions. First, following the guidelines for dogs and in accordance with previous studies, the authors divided the cats into three age groups (aged one year or younger, between one and six, and older than six) and calculated the proportion of cats with a detectable lesion on MRI in these groups. In the first group, 3/32 cats (9.4 per cent) had significant MRI abnormalities that were all consistent with congenital malformation; in the second group, only 5/92 (5.4 per cent) MRI scans were abnormal and in the third group, 15/ 65 (23.1 per cent) cats showed abnormal findings that were predominantly lesions of neoplastic origin. Second, to investigate the impact of age further, data were investigated as a continuous variable using receiver operating characteristic analysis. This indicated an optimal cut‐off age of five years, above which MRI abnormalities were more likely, with an increase in the odds of a significant structural lesion increasing by 14 per cent per year.
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In the second of this two‐part article we discuss the available treatment options for spinal cord injury. Remarkably, apart from surgical decompression for suitable candidate cases, there is a paucity of therapeutic choice and current drug therapies generally play a minor role. Prognosis is largely dependent on the severity of irreversible tissue destruction incurred, but the full extent of possible recovery may take many weeks to months to become apparent. In the short term, optimal care consists of correcting abnormalities in blood pressure and oxygenation. In the long‐term, recovery can best be promoted by high quality individualised rehabilitation therapy and allowing plenty of time.
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