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How to detect a sensory abnormality
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European Journal of Pain 12 (2008) 395–396 www.EuropeanJournalPain.com
Editorial
How to detect a sensory abnormality
Sensory examination with simple bedside tools is the most important part of the physical examination of patients suspected to suffer from neuropathic pain, because by definition neuropathic pain is a consequence of damage to the somatosensory system (Treede et al., Neurology, in press). Arguably, this notion applies to other chronic pain conditions as well (Baron and Binder, 2004). Neurologists have traditionally been skeptical about sensory findings because of their subjective nature. A recent meta-analysis, however, has shown that quantitative sensory testing (QST) and laser evoked potentials (LEPs) are validated as laboratory tests to supplement the sensory examination (Cruccu et al., 2004). Quantitative sensory testing (QST) becomes increasingly available as a laboratory test, as exemplified by the publication of the standard protocol (Rolke et al., 2006a) and the nationwide reference database (Rolke et al., 2006b) of the German Research Network on Neuropathic Pain (DFNS). In many places, QST can already be ordered by the physician to obtain supporting data for clinical decision making, and this technique may soon be as commonplace as EMG or MRI scan. In this issue of the European Journal of Pain, Ann-Sophie Leffler and Per Hansson (2008) report a retrospective analysis of bedside sensory examination (BE) and quantitative sensory testing (QST) in a group of 32 patients with neuropathic pain following nerve injury. This is a very important comparison, because QST should only be performed after a thorough clinical examination. Careful titration of the borders of sensory aberrations is a mandatory part of the bedside examination. These data are the foundation where to apply QST. Leffler and Hansson (2008) report that BE and QST gave the same finding in only half of the patients, and that bedside examination was more sensitive than QST in the other half. Discrepancies between bedside exami-
DOI of original article: 10.1016/j.ejpain.2007.08.009
nation and QST were more pronounced for tactile testing than for thermal testing. How to interpret these findings? At face value, these data might suggest that QST is not good for screening because of its low sensitivity. With a high specificity, QST would then be a logical confirmatory test after bedside examination. A sensory abnormality in bedside testing, however, was an inclusion criterion for this study. Thus, patients with subclinical sensory deficits, where QST might have been more sensitive than bedside examination, could by definition not be found in this retrospective analysis. LEPs, for example, have been shown to be sensitive to subclinical nociceptive deficits in multiple sclerosis (Spiegel et al., 2003). Left–right differences were the cornerstone in the bedside examination. Leffler and Hansson (2008) based their criteria for calling such a difference pathological on what they call ‘‘time-honored clinical decision making”, e.g. a 1 °C side difference for thermal detection thresholds. These criteria lack any solid scientific data derived from studies on the range of physiological side differences in healthy subjects. In fact, there is accumulating evidence that the normal nervous system comprises a variety of left–right perceptual asymmetries (Vallortigara, 2006). These include for example in animal studies a preferential use of the left or right visual hemifield during activities such as searching food or avoiding obstacles. In the somatosensory system, neuron counts of the dorsal root ganglia showed a left–right difference of up to 50% (Ygge et al., 1981). Consistent with these anatomical asymmetries, a standardized QST analysis in 180 healthy volunteers (Rolke et al., 2006b) revealed that the range of normal left–right differences (95% confidence interval) was a factor of 2.4 for thermal detection thresholds, consistent with findings throughout clinical electrophysiology. Thus, in older male patients, where the normal thermal detection threshold may be 3.0 °C, a 1.0 °C side difference is clearly within the normal range. Thus, the approach
1090-3801/$34 Ó 2007 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejpain.2007.11.008
396
Editorial / European Journal of Pain 12 (2008) 395–396
by Leffler and Hansson raises the question to what extent positive findings on bedside examination were only reflecting normal site-to-site variability and hence may have been false positive. The DFNS reference data (Rolke et al., 2006b) give some interesting findings with respect to the clinical use of QST: (1) Left–right differences were homogenous across levels (face, hand and foot), thus one single set of reference data is sufficient across all test sites. (2) Comparisons across different levels (face, hand and foot), however, did not yield any gain in sensitivity. Although left–right comparisons are a sensitive measure in neurology, such intraindividual comparisons fail when the mirror-image site is abnormal, too, as in polyneuropathies, multiple sclerosis etc. Thus, the approach recommended by Leffler and Hansson can be used only in select cases, where the contralateral site is 100% normal. In clinical reality, this is often not the case, if only due to comorbity of diabetes. Leffler and Hansson (2008) then go on to argue that QST reference data are only useful for group comparisons and not for interpretation of results in individual patients. This notion is at variance with our observations: one of the clinically most striking outcomes of the DFNS reference dataset was that left–right comparisons are more sensitive to detect deficits than absolute reference data, but hand–foot comparisons are not. The DFNS protocol with its z-transform takes into account test site, age and gender, and thus lends itself for an easy clinical interpretation on a single case basis. We would like to emphasize that titration of borders of the sensory aberrations, a key issue in the bedside examination, is a necessary prerequisite before QST, and more care should be taken to report those borders (Hansson, 2002; Rasmussen et al., 2004). With respect to the sensitivity and specificity of QST and bedside examination, the study by Leffler and Hansson (2008) is inconclusive, because their carefully selected cases inevitably also represent a selection bias. The margins between normal and pathological values for somatosensory side differences that are used in their study are assumptions based on clinical experience. Evidencebased data on the variability of biological systems are increasingly available and we think that they should be adopted in clinical studies. Finally, QST is not only a tool for group comparisons, but it gives clear conclusions both whether a given sensory finding is within normal variability for this test site, and whether the left–
right difference is within normal variability. These data can then be used in clinical decisions.
References Baron R, Binder A. Wie neuropathisch ist die Ischialgie? Das mixedpain-Konzept [How neuropathic is sciatica? – the mixed pain concept]. Orthopa¨de 2004;33(5):568–75. Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpa¨a¨ M, Jørum E, et al.. EFNS guidelines on neuropathic pain assessment. Eur J Neurol 2004;11:153–62. Hansson P. Neuropathic pain: clinical characteristics and diagnostic workup. Eur J Pain 2002;6(Suppl A):47–50. Leffler AS, Hansson P. Painful traumatic peripheral partial nerve injury – sensory dysfunction profiles comparing outcomes of bedside examination and quantitative sensory testing. Eur J Pain 2008;12:397–402. Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, et al.. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain 2006a;10:77–88. Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, et al.. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006b;123:231–43. Rasmussen PV, Sindrup SH, Jensen TS, Bach FW. Symptoms and signs in patients with suspected neuropathic pain. Pain 2004;110:461–9. Spiegel J, Hansen C, Baumga¨rtner U, Hopf HC, Treede RD. Sensitivity of laser-evoked potentials versus somatosensory evoked potentials in patients with multiple sclerosis. Clin Neurophysiol 2003;114:992–1002. Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: Redefinition and a grading system for clinical and research purposes. Neurology [in press], Pub Med PMID18003941. Vallortigara G. The evolutionary psychology of left and right: costs and benefits of lateralization. Dev Psychobiol 2006;48:418–27. Ygge J, Aldskogius H, Grant G. Asymmetries and symmetries in the number of thoracic dorsal root ganglia. J Comp Neurol 1981;202: 365–72.
Rolf-Detlef Treede Division of Neurophysiology, CBTM, Medical Faculty Mannheim, Ruprecht Karls University Heidelberg, Mannheim, Germany Tel.: +49 621 383 9926; fax: +49 621 383 9921 E-mail address: [email protected] Ralf Baron Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital of Schleswig-Holstein, Campus Kiel, Germany Available online 24 January 2008
European Journal of Pain 12 (2008) 395–396 www.EuropeanJournalPain.com
Editorial
How to detect a sensory abnormality
Sensory examination with simple bedside tools is the most important part of the physical examination of patients suspected to suffer from neuropathic pain, because by definition neuropathic pain is a consequence of damage to the somatosensory system (Treede et al., Neurology, in press). Arguably, this notion applies to other chronic pain conditions as well (Baron and Binder, 2004). Neurologists have traditionally been skeptical about sensory findings because of their subjective nature. A recent meta-analysis, however, has shown that quantitative sensory testing (QST) and laser evoked potentials (LEPs) are validated as laboratory tests to supplement the sensory examination (Cruccu et al., 2004). Quantitative sensory testing (QST) becomes increasingly available as a laboratory test, as exemplified by the publication of the standard protocol (Rolke et al., 2006a) and the nationwide reference database (Rolke et al., 2006b) of the German Research Network on Neuropathic Pain (DFNS). In many places, QST can already be ordered by the physician to obtain supporting data for clinical decision making, and this technique may soon be as commonplace as EMG or MRI scan. In this issue of the European Journal of Pain, Ann-Sophie Leffler and Per Hansson (2008) report a retrospective analysis of bedside sensory examination (BE) and quantitative sensory testing (QST) in a group of 32 patients with neuropathic pain following nerve injury. This is a very important comparison, because QST should only be performed after a thorough clinical examination. Careful titration of the borders of sensory aberrations is a mandatory part of the bedside examination. These data are the foundation where to apply QST. Leffler and Hansson (2008) report that BE and QST gave the same finding in only half of the patients, and that bedside examination was more sensitive than QST in the other half. Discrepancies between bedside exami-
DOI of original article: 10.1016/j.ejpain.2007.08.009
nation and QST were more pronounced for tactile testing than for thermal testing. How to interpret these findings? At face value, these data might suggest that QST is not good for screening because of its low sensitivity. With a high specificity, QST would then be a logical confirmatory test after bedside examination. A sensory abnormality in bedside testing, however, was an inclusion criterion for this study. Thus, patients with subclinical sensory deficits, where QST might have been more sensitive than bedside examination, could by definition not be found in this retrospective analysis. LEPs, for example, have been shown to be sensitive to subclinical nociceptive deficits in multiple sclerosis (Spiegel et al., 2003). Left–right differences were the cornerstone in the bedside examination. Leffler and Hansson (2008) based their criteria for calling such a difference pathological on what they call ‘‘time-honored clinical decision making”, e.g. a 1 °C side difference for thermal detection thresholds. These criteria lack any solid scientific data derived from studies on the range of physiological side differences in healthy subjects. In fact, there is accumulating evidence that the normal nervous system comprises a variety of left–right perceptual asymmetries (Vallortigara, 2006). These include for example in animal studies a preferential use of the left or right visual hemifield during activities such as searching food or avoiding obstacles. In the somatosensory system, neuron counts of the dorsal root ganglia showed a left–right difference of up to 50% (Ygge et al., 1981). Consistent with these anatomical asymmetries, a standardized QST analysis in 180 healthy volunteers (Rolke et al., 2006b) revealed that the range of normal left–right differences (95% confidence interval) was a factor of 2.4 for thermal detection thresholds, consistent with findings throughout clinical electrophysiology. Thus, in older male patients, where the normal thermal detection threshold may be 3.0 °C, a 1.0 °C side difference is clearly within the normal range. Thus, the approach
1090-3801/$34 Ó 2007 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejpain.2007.11.008
396
Editorial / European Journal of Pain 12 (2008) 395–396
by Leffler and Hansson raises the question to what extent positive findings on bedside examination were only reflecting normal site-to-site variability and hence may have been false positive. The DFNS reference data (Rolke et al., 2006b) give some interesting findings with respect to the clinical use of QST: (1) Left–right differences were homogenous across levels (face, hand and foot), thus one single set of reference data is sufficient across all test sites. (2) Comparisons across different levels (face, hand and foot), however, did not yield any gain in sensitivity. Although left–right comparisons are a sensitive measure in neurology, such intraindividual comparisons fail when the mirror-image site is abnormal, too, as in polyneuropathies, multiple sclerosis etc. Thus, the approach recommended by Leffler and Hansson can be used only in select cases, where the contralateral site is 100% normal. In clinical reality, this is often not the case, if only due to comorbity of diabetes. Leffler and Hansson (2008) then go on to argue that QST reference data are only useful for group comparisons and not for interpretation of results in individual patients. This notion is at variance with our observations: one of the clinically most striking outcomes of the DFNS reference dataset was that left–right comparisons are more sensitive to detect deficits than absolute reference data, but hand–foot comparisons are not. The DFNS protocol with its z-transform takes into account test site, age and gender, and thus lends itself for an easy clinical interpretation on a single case basis. We would like to emphasize that titration of borders of the sensory aberrations, a key issue in the bedside examination, is a necessary prerequisite before QST, and more care should be taken to report those borders (Hansson, 2002; Rasmussen et al., 2004). With respect to the sensitivity and specificity of QST and bedside examination, the study by Leffler and Hansson (2008) is inconclusive, because their carefully selected cases inevitably also represent a selection bias. The margins between normal and pathological values for somatosensory side differences that are used in their study are assumptions based on clinical experience. Evidencebased data on the variability of biological systems are increasingly available and we think that they should be adopted in clinical studies. Finally, QST is not only a tool for group comparisons, but it gives clear conclusions both whether a given sensory finding is within normal variability for this test site, and whether the left–
right difference is within normal variability. These data can then be used in clinical decisions.
References Baron R, Binder A. Wie neuropathisch ist die Ischialgie? Das mixedpain-Konzept [How neuropathic is sciatica? – the mixed pain concept]. Orthopa¨de 2004;33(5):568–75. Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpa¨a¨ M, Jørum E, et al.. EFNS guidelines on neuropathic pain assessment. Eur J Neurol 2004;11:153–62. Hansson P. Neuropathic pain: clinical characteristics and diagnostic workup. Eur J Pain 2002;6(Suppl A):47–50. Leffler AS, Hansson P. Painful traumatic peripheral partial nerve injury – sensory dysfunction profiles comparing outcomes of bedside examination and quantitative sensory testing. Eur J Pain 2008;12:397–402. Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, et al.. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain 2006a;10:77–88. Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, et al.. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006b;123:231–43. Rasmussen PV, Sindrup SH, Jensen TS, Bach FW. Symptoms and signs in patients with suspected neuropathic pain. Pain 2004;110:461–9. Spiegel J, Hansen C, Baumga¨rtner U, Hopf HC, Treede RD. Sensitivity of laser-evoked potentials versus somatosensory evoked potentials in patients with multiple sclerosis. Clin Neurophysiol 2003;114:992–1002. Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: Redefinition and a grading system for clinical and research purposes. Neurology [in press], Pub Med PMID18003941. Vallortigara G. The evolutionary psychology of left and right: costs and benefits of lateralization. Dev Psychobiol 2006;48:418–27. Ygge J, Aldskogius H, Grant G. Asymmetries and symmetries in the number of thoracic dorsal root ganglia. J Comp Neurol 1981;202: 365–72.
Rolf-Detlef Treede Division of Neurophysiology, CBTM, Medical Faculty Mannheim, Ruprecht Karls University Heidelberg, Mannheim, Germany Tel.: +49 621 383 9926; fax: +49 621 383 9921 E-mail address: [email protected] Ralf Baron Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital of Schleswig-Holstein, Campus Kiel, Germany Available online 24 January 2008