Fatigue is one of the most common symptoms in multiple sclerosis (MS), with a major impact on patients’ quality of life. Currently, treatment proceeds by trial and error with limited success, probably due to the presence of multiple different underlying mechanisms. Recent neuroscientific advances offer the potential to develop tools for differentiating these mechanisms in individual patients and ultimately provide a principled basis for treatment selection. However, development of these tools for differential diagnosis will require guidance by pathophysiological and cognitive theories that propose mechanisms which can be assessed in individual patients. This article provides an overview of contemporary pathophysiological theories of fatigue in MS and discusses how the mechanisms they propose may become measurable with emerging technologies and thus lay a foundation for future personalised treatments.

To describe different currently available tests of multimodal intraoperative monitoring (MIOM) used in spine and spinal cord surgery indicating the technical parameters, application and interpretation as an easy understanding systematic overview to help implementation of MIOM and improve communication between neurophysiologists and spine surgeons. This article aims to give an overview and proposal of the different MIOM-techniques as used daily in spine and spinal cord surgery at our institution. Intensive research in neurophysiology over the past decades has lead to a profound understanding of the spinal cord, nerve functions and their intraoperative functional evaluation in anaesthetised patients. At present, spine surgeons and neurophysiologist are faced with 1,883 publications in PubMed on spinal cord monitoring. The value and the limitations of single monitoring methods are well documented. The diagnostic power of the multimodal approach in a larger study population in spine surgery, as measured with sensitivity and specificity, is dealt with elsewhere in this supplement (Sutter et al. in Eur Spine J Suppl, 2007). This paper aims to give a detailed description of the different modalities used in this study. Description of monitoring techniques of the descending and ascending spinal cord and nerve root pathways by motor evoked potentials of the spinal cord and muscles elicited after transcranial electrical motor cortex, spinal cord, cauda equina and nerve root stimulation, continuous EMG, sensory cortical and spinal evoked potentials, as well as direct spinal cord evoked potentials applied on 1,017 patients.The method of MIOM, continuously adapted according to the site, stage of surgery and potential danger to nerve tissues, proved to be applicable with online results, reliable and furthermore teachable.

SUMMARY The purpose of the present paper is twofold. Firstly, to compare the accuracy per unit cost achieved by two different methods of subsampling micrographs from sections of a material for stereology when the sections cannot be analysed as a whole at the required magnification. Secondly, to illustrate, by means of real data, the application of some of the methods and formulae proposed in the companion paper (Cruz‐Orive & Weibel, 1981) for estimating ratios at the electron microscopic level. The final estimates of a same ratio obtained by either subsampling method (namely systematic (SQ) and systematic area‐weighted quadrats (SAWQ)) agreed in the mean and they were about equally precise. The former fact indicates that the new SAWQ method is at least as reliable as the SQ method as far as bias is concerned. The latter result is a consequence of the well‐known fact that subsampling is relatively unimportant in two‐stage sampling. Yet, SAWQ subsampling enjoys definite practical advantages over other subsampling methods in certain situations.

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