Early diagnosis of amyotrophic lateral sclerosis by threshold tracking and conventional transcranial magnetic stimulation

© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Background and purpose: Short-interval intracortical inhibition by threshold tracking (T-SICI) has been proposed as a diagnostic tool for amyotrophic lateral sclerosis (ALS) but has not been compared directly with conventional amplitude measurements (A-SICI). This study compared A-SICI and T-SICI for sensitivity and clinical usefulness as biomarkers for ALS. Methods: In all, 104 consecutive patients referred with suspicion of ALS were prospectively included and were subsequently divided into 62 patients with motor neuron disease (MND) and 42 patient controls (ALS mimics) by clinical follow-up. T-SICI and A-SICI recorded in the first dorsal interosseus muscle (index test) were compared with recordings from 53 age-matched healthy controls. The reference standard was the Awaji criteria. Clinical scorings, conventional nerve conduction studies and electromyography were also performed on the patients. Results: Motor neuron disease patients had significantly reduced T-SICI and A-SICI compared with the healthy and patient control groups, which were similar. Sensitivity and specificity for discriminating MND patients from patient controls were high (areas under the receiver operating characteristic curves 0.762 and 0.810 for T-SICI and A-SICI respectively at 1-3.5 ms). Paradoxically, T-SICI was most reduced in MND patients with the fewest upper motor neuron (UMN) signs (Spearman ρ = 0.565, p = 4.3 × 10-6 ). Conclusions: Amplitude-based measure of cortical inhibition and T-SICI are both sensitive measures for the detection of cortical involvement in MND patients and may help early diagnosis of ALS, with T-SICI most abnormal before UMN signs have developed. The gradation in T-SICI from pathological facilitation in patients with minimal UMN signs to inhibition in those with the most UMN signs may be due to progressive degeneration of the subset of UMNs experiencing facilitation.info:eu-repo/semantics/publishedVersio

Tilgængelighedsanalyse – en arkæologisk metode?

Access analysis – an archaeological method? Access analysis is a methodological instrument for analysing spatial structures developed by B. Hillier and J. Hanson (Hillier & Hanson 1984). This form of analysis was defined in the middle of the 1980s with reference to working up architectural plans. As the method does not only operate with the physical relations, but also regards these as a constitution of social circumstances and ideas, the method has also been employed by archaeologists. If one is able to understand social structures by reading and analysing spatial structures, one is working oneself into a central field of archaeology.The method takes a building’s spatial structure as its starting point. In order to carry out an analysis like this it is necessary to know the complete structure of a building. According to a developed scheme with symbols representing the different building elements, the spatial structure is translated into gamma-maps. According to the hierarchic position of the depth of a single element in proportion to the whole building, these maps are translated into justified gamma-maps. Access to the whole building as well as to the individual rooms in reciprocal relation is a prerequisite for the analysis. That is, justified gamma-maps graphically represent a building’s spatial structures and can be interpreted from the structures’ reciprocal relations (Figs. 1-5).However, as the method was not defined and developed with reference to an archaeological context, there are problematic elements in translating the method from its original context into archaeology. Various elements will be ignored when using access analysis as a methodological instrument in archaeology.There are problematic elements in reducing the spatial structure of a building to symbols with simplified connotative characters in connection with the transcription into gamma-maps. First of all, the relative sizes and shapes of the rooms will be ignored. They cannot simply be characterized as standardized sizes (Fig. 6).Further, not only physical elements are overlooked in gamma-maps and justified gamma-maps. Several elements will not appear through spatial structures and will thus not be taken into consideration in Hillier & Hanson’s analytic model. Examples are possible room decorations, symbolism in location and room distribution of a building, tradition and building material. Several of these elements would not be recognized in an archaeological excavation, but are likely to have been of importance in contemporary culture. The problem with these elements is that even if they were recognized in the archaeological material, their significance practically could not be established without non-archaeological information. It is in fact a previous knowledge or concept of a society that contributes to interpretation of a building’s social structures in Hillier & Hanson’s analytic model.As access analysis focuses on physical relations, a vital aspect is lacking that makes buildings what they are for both society and individuals: the human use and understanding of a building. Also, the aspect of time is overlooked in gamma-maps. The context in which a building is to be read and understood is changing throughout time. This is clearly a weakness in this way of analysing. Access analysis can be characterized as static, as opposed to the social reality in which a building operates. And this very conflict influences the result of the analysis in a negative way.An example of the practical use of access analysis is Neil Price’s article, ”House and Home in Viking Age Iceland. Cultural Expression in Scandinavian Colonial Architecture.” With a starting point in access analysis, he analyses Viking houses in Iceland. His aim is to find a Scandinavian idea of the concept of home. He does point out how spatial structures of the houses change through time, and how active factors must be a result of the inhabitants and their social structure. However, this is no more than one can tell just by the spatial structures of the houses and the theory of the method. Conclusions based only on the access analysis method as in this case seem to be no more than an argumentative circle. As shown by this example, it is important to recognize the limitations of the method when using it for archaeology. As mentioned above, several other factors must be taken into consideration.Theoretically, the method implies that one agrees with Hillier & Hanson that there is a relatively direct relationship between physical and social structures. Even at this point there are objections as to the use of access analysis and its basic theory within archaeology.Even though the gamma-maps represent building structures graphically in a way that permits a relatively easy comparison between houses, the method has its limitations. And the conclusion must be that Hillier & Hanson do not provide a general theory for analysing spatial structures and the social structures behind these.Kirsten Pugdahl PedersenAarhus UniversitetTranslated by Annette Lerche Troll