Positive Prognostication from Median-Nerve Somatosensory Evoked Cortical Potentials

Background

The bilateral absence of the cortical N20 median-nerve somatosensory evoked potential (SSEP) is a strong predictor of poor outcome from coma. However, when N20s are present, accurate prognostication is challenging. Here, we investigated the potential for later SSEP components to help disambiguate outcome in these cases.

Methods

In a retrospective review of data from two intensive care units, the amplitudes and latencies of the N20, P25, and N35 components of 28 patients in coma were quantified and related to outcome at discharge from primary care (average 1-month post-injury). Only patients who had survived primary care were included in order to avoid self-fulfilling prophecies, and to focus outcome prediction on those patients with relatively present SSEPs.

Results

The amplitudes of the N20 and N35 components (averaged across hemispheres) significantly predicted the range of outcomes beyond death. Abnormal amplitudes of the N20 and N35—as derived from a healthy control group—were significantly associated with poor outcome. The relative latencies of the cortical components were not related to outcome.

Conclusions

While it is well documented that absent SSEPs are highly predictive of poor outcome, the current data indicate that the relative preservation (absolute amplitude) of “present” N20 and N35 SSEP components can also provide predictive value and thereby inform clinicians and families with decision-making in coma. Further prospective study will elucidate the relative contributions of etiology to the predictive power of these SSEP measures.     

Genome‐wide transcriptome analyses reveal p53 inactivation mediated loss of miR‐34a expression in malignant peripheral nerve sheath tumours

Malignant peripheral nerve sheath tumours (MPNSTs) are aggressive soft tissue tumours that occur either sporadically or in patients with neurofibromatosis type 1. The malignant transformation of the benign neurofibroma to MPNST is incompletely understood at the molecular level. We have determined the gene expression signature for benign and malignant PNSTs and found that the major trend in malignant transformation from neurofibroma to MPNST consists of the loss of expression of a large number of genes, rather than widespread increase in gene expression. Relatively few genes are expressed at higher levels in MPNSTs and these include genes involved in cell proliferation and genes implicated in tumour metastasis. In addition, a gene expression signature indicating p53 inactivation is seen in the majority of MPNSTs. Subsequent microRNA profiling of benign and malignant PNSTs indicated a relative down‐regulation of miR‐34a in most MPNSTs compared to neurofibromas. In vitro studies using the cell lines MPNST‐14 (NF1 mutant) and MPNST‐724 (from a non‐NF1 individual) show that exogenous expression of p53 or miR‐34a promotes apoptotic cell death. In addition, exogenous expression of p53 in MPNST cells induces miR‐34a and other miRNAs. Our data show that p53 inactivation and subsequent loss of expression of miR‐34a may significantly contribute to the MPNST development. Collectively, our findings suggest that deregulation of miRNAs has a potential role in the malignant transformation process in peripheral nerve sheath tumours. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Airway wall geometry in asthma and nonasthmatic eosinophilic bronchitis

Background: Variable airflow obstruction and airway hyperresponsiveness (AHR) are features of asthma, which are absent in nonasthmatic eosinophilic bronchitis (EB). Airway remodelling is characteristic of both conditions suggesting that remodelling and airway dysfunction are disassociated, but whether the airway geometry differs between asthma and nonasthmatic EB is uncertain. Methods: We assessed airway geometry by computed tomography (CT) imaging in asthma vs EB. A total of 12 subjects with mild–moderate asthma, 14 subjects with refractory asthma, 10 subjects with EB and 11 healthy volunteers were recruited. Subjects had a narrow collimation (0.75 mm) CT scan from the aortic arch to the carina to capture the right upper lobe apical segmental bronchus (RB1). In subjects with asthma and EB, CT scans were performed before and after a 2‐week course of oral prednisolone (0.5 mg/kg). Results: Mild–moderate and refractory asthma were associated with RB1 wall thickening in contrast to subjects with nonasthmatic EB who had maintained RB1 patency without wall thickening [mean (SD) % wall area and luminal area mild‐t0‐moderate asthma 67.7 (7.3)% and 6.6 (2.8) mm²/m², refractory asthma 67.3 (5.6)% and 6.7 (3.4) mm²/m², healthy control group 59.7 (6.3)% and 8.7 (3.8) mm²/m², EB 61.4 (7.8)% and 11.1 (4.6) mm²/m² respectively; P < 0.05]. Airway wall thickening of non‐RB1 airways generation three to six was a feature of asthma only. There was no change in airway geometry of RB1 after prednisolone. Proximal airway wall thickening was associated with AHR in asthma (r = ?0.56; P = 0.02). Conclusions: Maintained airway patency in EB may protect against the development of AHR, whereas airway wall thickening may promote AHR in asthma.