- Email: [email protected]
Thalamic perfusion in reflex sympathetic dystrophy syndrome
CORRESPONDENCE
Studies of mutations in hypoxanthineguanine phosphoribosyltransferase and glycophorin A have shown no significant increases in the Sellafield workers3,4 in contrast with the raised frequencies seen in those exposed to radiation from the atomic bombs. Also, animal studies have established a reduction in effect for chronic exposure on gonadal cells, which indicates that the genetic effect of chronic exposure to spermatogonia is about a third that induced by acute irradiation.5 Thus, whether the statistical association found by Parker and colleagues represents a real biological effect is doubtful. E Janet Tawn Westlakes Research Institute, Cumbria CA24 3JY, UK 1
2
3
4
5
Parker L, Pearce MS, Dickinson HO, et al. Stillbirths among the offspring of male radiation workers at the Sellafield nuclear reprocessing plant. Lancet 1999; 354: 1407–14. Neel JV, Schull WJ. The children of Atomic bomb survivors. Washington DC: Natl Acad Press, 1991. Tucker JD, Tawn EJ, Holdsworth D, et al. Biological dosimetry of radiation wokers at the Sellafield nuclear facility. Radiat Res 1997; 148: 216–26. Cole J, Arlett CF, Green MHL, et al. Mutant frequencies in workers at the Sellafield installation. Health Phys 1995; 68: 388–93. United Nations scientific committee on the effects of atomic radiation, sources and effects of ionising radiation (UNSCEAR 1993 Report). New York: United Nations: 1993.
Thalamic perfusion in reflex sympathetic dystrophy syndrome Sir—Mitsutaka Fukumoto and colleagues (Nov 20, p 1790)1 used single photon emission computed tomography (SPECT) to visualise changes in thalamic perfusion contralateral to the side of pain in patients with reflex sympathetic dystrophy syndrome (RSDS). However, before postulating new central mechanisms of pathogenesis of RSDS, the implication that the sympathetic nervous system has a part in its aetiology needs to be reconsidered. The International Association for the Study of Pain has defined RSDS under a heading of complex regional pain syndrome (CRPS) type I as opposed to causalgia, involving nerve damage, which is CRPS type II.2 Hence, sympathetic instability would not be expected to correlate with thalamic perfusion as Fukumoto and colleagues found in their study.
494
Fukumoto and colleagues found a strong correlation between contralateral thalamic perfusion and time since onset of symptoms, suggesting an initial increase in thalamic activity and then a gradual decrease. A similar spectrum of change in thalmic activity has been reported in other chronic pain conditions, from an increase in thalamic activity in central post-stroke pain3 to a decrease in thalamic activity in chronic neuropathic pain.4 Care must be taken when interpreting the results from one point in time and from a few patients. However, the possibility of temporal variation in thalamic activity with ongoing chronic pain may explain the variation in thalamic perfusion seen in other studies3,4 previously explained as heterogeneity of chronic pain pathophysiology. If such gross changes do occur in the central pain pathways over time, interpretation of functional brain imaging will be fraught with difficulties because results would be affected by time from onset of symptoms. Reversal of changes in thalamic activity by alteration of sensory input, rather than monitoring changes per se, may yield information on the pathogenesis of chronic pain. In a study by Di Piero and colleagues,5 perfusion in the contralateral hemithalamus was restored in five patients with unilateral, severe, chronic cancer pain by interrupting the ascending spinothalamic tract of the spinal cord. Hence, it may be difficult to separate changes in the thalamus from neuronal activity of afferent thalamic connections. Emma Chojnowska Pain Clinic, Frenchay Hospital, Frenchay, Bristol BS16 1LE, UK 1
2
3
4
5
Fukumoto M, Ushida T, Zinchuk VS, Yamamoto H, Yoshida S. Contralateral thalamic perfusion in patients with reflex sympathetic dystrophy syndrome. Lancet 1999; 354: 1790–91. Mersky H, Bogduk N, eds. Classification of chronic pain, 2nd edn. Seattle: ISAP Press, 1994. Cesaro P, Mann MW, Moretti JL, et al. Central pain and thalamic hyperactivity: a single photon emission computerized tomographic scan. Pain 1991; 47: 329–36. Iadarola MJ, Max MB, Berman KF, et al. Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain. Pain 1995; 63: 55–64. Di Piero V, Jones AKP, Iannotti F, et al. Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy. Pain 1991; 46: 9–12.
Sir—In their study involving singlephoton emission computed tomography (SPECT), Fukumoto and colleagues1 describe a correlation
between contralateral thalamic iodoamphetamine uptake index and time from onset of reflex sympathetic dystrophy syndrome (RSDS). Their findings help us understand more about RSDS and the plasticity of the brain in general. Their paper may have a widespread impact on the world of neuroscience. We urge Fukumoto and colleagues to test their findings in a larger patient group stratified in the different timely subgroups and to re-evaluate the data by Statistical Parametric Mapping (SPM) to be able to carry out the region-of-interest (ROI) analysis. This SPM software package, freely available via the Internet, comes from the Wellcome Department of Cognitive Neurology, London, UK, and has helped standardise measurement and data analysis in functional neuroimaging. This package not only spatially normalises the images to the stereotaxic atlas by Talairach and Tournoux,2 but can also carry out statistical analyses on study groups on a voxel-by-voxel basis.3 This package allows reliable and objective image handling that could improve interstudy variability, which often causes difficulties in ROI analysis. Cerebral reactions to peripheral diseases can also be found in patients with chronic symptoms after a distortion of the cervical spine. Such distortion can result in perfusion deficits in the posterior parietal occipital region, possibly because of nociceptive afferents from the upper cervical spine causing an increased vasopeptide production, which results in a vasoconstriction of the major cerebral arteries and the vulnerable posterior watershed region.4 Cerebral de-afferentiation phenomena can also be found in patients after a spinal cord injury. In such injuries glucose metabolism might be altered because of a reduction or loss of sensorimotor function and increased glucose metabolism in brain regions involved in attention and initiation of movement, possibly as a result of secondary disinhibition of these regions.5 Andreas Otte Obere Lachen 10, D-79110 Freiburg, Germany (e-mail: [email protected]) 1
2
3
Fukumoto M, Ushida T, Zinchuk VS, Yamamoto H, Yoshida S. Contralateral thalamic perfusion in patients with reflex sympathetic dystrophy syndrome. Lancet 1999; 354: 1790–91. Talairach J, Tournoux P. Co-planar Stereotaxic Atlas of the Human Brain. Stuttgart: Thieme, 1988. Friston KJ, Holmes AP, Worsley KJ, Poline JB, Frith CD, Frackowiak RSJ. Statistical parametric maps in functional imaging: a general approach. Hum Brain Mapping 1995; 2: 189–210.
THE LANCET • Vol 355 • February 5, 2000
CORRESPONDENCE 4
5
Otte A, Mueller-Brand J, Fierz L. Brain SPECT findings in late whiplash syndrome. Lancet 1995; 345: 1513–14. Roelcke U, Curt A, Otte A, Missimer J, Maguire JP, Dietz V, Leenders KL. Influence of spinal cord injury on cerebral sensorimotor systems: a PET study. J Neurol Neurosurg Psychiatry 1997; 62: 61–65.
Sir—The increased thalamic perfusion detected by SPECT imaging described by Fukumoto and co-workers1 is an interesting observation but we doubt it sheds light on the pathogenesis of reflex sympathetic dystrophy syndrome (RSDS). An increase in thalamic perfusion simply indicates increased metabolic activity, which in turn reflects the extra sensory input from continuous pain stimuli, and this decreases over time as an adaptive response. Unfortunately, the investigators used healthy individuals as controls, but a control group of patients with other types of acute pain in the limbs would have created a far more relevant set of results. The cause and pathology of RSDS remains controversial.2 It is seen after minor injuries and is often associated and prolonged by medico-legal litigation. An identical condition can be seen in holy men in India who as a sign of their faith, hold up one arm in perpetuity. After some years, the limb shows the signs of RSDS—shiny hairless fragile skin and trophic changes in the nails. Immobilisation for any reason, from hemiplegia to choice, seems to result in this phenomenon. High-tech evaluations of the brain simply map activity and should not be interpreted as reflecting underlying pathogenesis. John W Norris, Alan West Sunnybrook & Women’s College Health Sciences Centre, University of Toronto Clinic, Toronto, Ontario M4N 3M5, Canada (e-mail: [email protected]) 1
2
Fukumoto M, Ushida T, Zinchuk VS, Yamamoto Y, Yoshida S. Contralateral thalamic perfusion in patients with reflex sympathetic dystrophy syndrome. Lancet 1999; 354: 1790–91. Wasner G, Backonja M-M, Baron R. Traumatic neuralgias. In: Backonja M-M, ed. Neurologic clinics. Philadelphia: WB Saunders, 1998: 851–68.
Authors’ reply Sir—Emma Chojnowska attracts our attention to the terminology used to characterise the complex regional pain syndrome (CRPS). Indeed, reflex sympathetic dystrophy syndrome (RSDS) is a CRPS, because it is a pain syndrome that does not involve the damage of nerves. Causalgia, on the other hand, does involve nerve damage. In our study, we followed this classification strictly and excluded
THE LANCET • Vol 355 • February 5, 2000
patients with a history of damaged nerves. Therefore, the study was focused on pure RSDS patients. Chojnowska says that no correlation should be expected between variations of thalamic perfusion and sympathetic instability found in patients with RSDS. To clinicians dealing with patients with CRPS this assumption is an over simplification. Both types of CRPS do show signs of sympathetic instability. Chojnowska cites two papers that reported changes in thalamic perfusion in patients with peripheral neuropathies and central post-stroke pain.1,2 The study by Iadarola and colleagues1 showed decrease in contralateral thalamic perfusion in patients with chronic neuropathic pain for more than 2 years, and their findings are comparable with our findings from the group of patients with a long-term RSDS. The results of the study by Cesaro and colleagues2 cannot serve as an appropriate comparison with ours because patients analysed by Cesaro’s group had had a cerebral vascular accident. The paper by Di Piero and colleages,3 which was cited by Chojnowska should be interpreted carefully because functional imaging of the brain for unilateral peripheral pain due to metastatic cancer was analysed. Because computed tomography scan was used to assess the state of the brain, the possibility that non-detected microscopic foci of metastatic dissemination contributed to the chronic pain described in this study cannot be ruled out. Undoubtedly, testing our results in a larger group and re-evaluation of the data with Statistical Parametric Mapping (SPM), as suggested by Andreas Otte, would be useful both for better understanding of the essence of reported data and optional functional neuroimaging. While re-evaluation of the findings by SPM does not represent any difficulties, testing them in a larger patient group is much more complicated. It is very difficult to find a large number of patients who have RSDS, but who do not have neurological and psychiatric dysfunction. We believe that studying the pathogenesis of noxious input from the periphery will prove to be important to our understanding of the mechanisms of brain plasticity. In patients with RSDS, the evaluation of the state of glucose metabolism may provide clues to a better understanding of this disorder. John Norris and Alan West suggest that the best possible controls for a
study of the pathogenesis of RSDS would be patients with acute pain in the limbs. Such controls would enable the direct comparison of thalamic perfusion in patients RSDS and those without RSDS. We expect that in the acute phase of RSDS, thalamic perfusion will probably be increased and will then gradually decrease to levels similar to those before the injury. However, such controls have their own limitations, including incomparable types of traumatic injury, different extents of injury, and the fact that the patients with acute traumatic pain may not be able to undergo single photon emission computed tomography at the peak of pain, when the most valuable information about the state of thalamic perfusion is expected. Therefore, the data obtained from such controls, while obviously useful, will probably still require another control group for comparison. *Mitsutaka Fukumoto, Takahiro Ushida, Vadim S Zinchuk, Hiroshi Yamamoto, Shoji Yoshida Departments of *Radiology, Orthopaedics, and Anatomy and Cell Biology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan (e-mail: [email protected]) 1
2
3
Iadarola NJ, Max MB, Berman KF, et al. Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain. Pain 1995; 63: 55–64. Cesaro P, Mann MW, Moretti JL, et al. Central pain and thalamic hyperactivity: a single photon emission computerised tomographic study. Pain 1991; 47: 329–36. Di Piero V, Jones AKP, Iannotti F, et al. Chronic pain: a PET study of the central affected of percutaneous high cervical cordotomy. Pain 1991; 46: 9–12.
Prevalence of multiple system atrophy Sir—A Shrag and colleagues (Nov 20, p 1771)1 report the prevalence of multiple system atrophy (MSA) and progressive supranuclear palsy. MSA is a sporadic neurodegenerative disease that produces a variable combination of dopa-unresponsive Parkinson’s disease, autonomic failure, and cerebellar and pyramidal signs. The epidemiology of such a rare and severe disease is challenging: necropsy studies are biased towards atypical cases of Parkinson’s disease that may overestimate the frequency of MSA, and population-based studies are limited by the low number of cases detected. Shrag and colleagues detected two possible and two probable cases of MSA through the computerised records of 12 general practices (population at risk 121 608). Moreover, three of 1190
495
Studies of mutations in hypoxanthineguanine phosphoribosyltransferase and glycophorin A have shown no significant increases in the Sellafield workers3,4 in contrast with the raised frequencies seen in those exposed to radiation from the atomic bombs. Also, animal studies have established a reduction in effect for chronic exposure on gonadal cells, which indicates that the genetic effect of chronic exposure to spermatogonia is about a third that induced by acute irradiation.5 Thus, whether the statistical association found by Parker and colleagues represents a real biological effect is doubtful. E Janet Tawn Westlakes Research Institute, Cumbria CA24 3JY, UK 1
2
3
4
5
Parker L, Pearce MS, Dickinson HO, et al. Stillbirths among the offspring of male radiation workers at the Sellafield nuclear reprocessing plant. Lancet 1999; 354: 1407–14. Neel JV, Schull WJ. The children of Atomic bomb survivors. Washington DC: Natl Acad Press, 1991. Tucker JD, Tawn EJ, Holdsworth D, et al. Biological dosimetry of radiation wokers at the Sellafield nuclear facility. Radiat Res 1997; 148: 216–26. Cole J, Arlett CF, Green MHL, et al. Mutant frequencies in workers at the Sellafield installation. Health Phys 1995; 68: 388–93. United Nations scientific committee on the effects of atomic radiation, sources and effects of ionising radiation (UNSCEAR 1993 Report). New York: United Nations: 1993.
Thalamic perfusion in reflex sympathetic dystrophy syndrome Sir—Mitsutaka Fukumoto and colleagues (Nov 20, p 1790)1 used single photon emission computed tomography (SPECT) to visualise changes in thalamic perfusion contralateral to the side of pain in patients with reflex sympathetic dystrophy syndrome (RSDS). However, before postulating new central mechanisms of pathogenesis of RSDS, the implication that the sympathetic nervous system has a part in its aetiology needs to be reconsidered. The International Association for the Study of Pain has defined RSDS under a heading of complex regional pain syndrome (CRPS) type I as opposed to causalgia, involving nerve damage, which is CRPS type II.2 Hence, sympathetic instability would not be expected to correlate with thalamic perfusion as Fukumoto and colleagues found in their study.
494
Fukumoto and colleagues found a strong correlation between contralateral thalamic perfusion and time since onset of symptoms, suggesting an initial increase in thalamic activity and then a gradual decrease. A similar spectrum of change in thalmic activity has been reported in other chronic pain conditions, from an increase in thalamic activity in central post-stroke pain3 to a decrease in thalamic activity in chronic neuropathic pain.4 Care must be taken when interpreting the results from one point in time and from a few patients. However, the possibility of temporal variation in thalamic activity with ongoing chronic pain may explain the variation in thalamic perfusion seen in other studies3,4 previously explained as heterogeneity of chronic pain pathophysiology. If such gross changes do occur in the central pain pathways over time, interpretation of functional brain imaging will be fraught with difficulties because results would be affected by time from onset of symptoms. Reversal of changes in thalamic activity by alteration of sensory input, rather than monitoring changes per se, may yield information on the pathogenesis of chronic pain. In a study by Di Piero and colleagues,5 perfusion in the contralateral hemithalamus was restored in five patients with unilateral, severe, chronic cancer pain by interrupting the ascending spinothalamic tract of the spinal cord. Hence, it may be difficult to separate changes in the thalamus from neuronal activity of afferent thalamic connections. Emma Chojnowska Pain Clinic, Frenchay Hospital, Frenchay, Bristol BS16 1LE, UK 1
2
3
4
5
Fukumoto M, Ushida T, Zinchuk VS, Yamamoto H, Yoshida S. Contralateral thalamic perfusion in patients with reflex sympathetic dystrophy syndrome. Lancet 1999; 354: 1790–91. Mersky H, Bogduk N, eds. Classification of chronic pain, 2nd edn. Seattle: ISAP Press, 1994. Cesaro P, Mann MW, Moretti JL, et al. Central pain and thalamic hyperactivity: a single photon emission computerized tomographic scan. Pain 1991; 47: 329–36. Iadarola MJ, Max MB, Berman KF, et al. Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain. Pain 1995; 63: 55–64. Di Piero V, Jones AKP, Iannotti F, et al. Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy. Pain 1991; 46: 9–12.
Sir—In their study involving singlephoton emission computed tomography (SPECT), Fukumoto and colleagues1 describe a correlation
between contralateral thalamic iodoamphetamine uptake index and time from onset of reflex sympathetic dystrophy syndrome (RSDS). Their findings help us understand more about RSDS and the plasticity of the brain in general. Their paper may have a widespread impact on the world of neuroscience. We urge Fukumoto and colleagues to test their findings in a larger patient group stratified in the different timely subgroups and to re-evaluate the data by Statistical Parametric Mapping (SPM) to be able to carry out the region-of-interest (ROI) analysis. This SPM software package, freely available via the Internet, comes from the Wellcome Department of Cognitive Neurology, London, UK, and has helped standardise measurement and data analysis in functional neuroimaging. This package not only spatially normalises the images to the stereotaxic atlas by Talairach and Tournoux,2 but can also carry out statistical analyses on study groups on a voxel-by-voxel basis.3 This package allows reliable and objective image handling that could improve interstudy variability, which often causes difficulties in ROI analysis. Cerebral reactions to peripheral diseases can also be found in patients with chronic symptoms after a distortion of the cervical spine. Such distortion can result in perfusion deficits in the posterior parietal occipital region, possibly because of nociceptive afferents from the upper cervical spine causing an increased vasopeptide production, which results in a vasoconstriction of the major cerebral arteries and the vulnerable posterior watershed region.4 Cerebral de-afferentiation phenomena can also be found in patients after a spinal cord injury. In such injuries glucose metabolism might be altered because of a reduction or loss of sensorimotor function and increased glucose metabolism in brain regions involved in attention and initiation of movement, possibly as a result of secondary disinhibition of these regions.5 Andreas Otte Obere Lachen 10, D-79110 Freiburg, Germany (e-mail: [email protected]) 1
2
3
Fukumoto M, Ushida T, Zinchuk VS, Yamamoto H, Yoshida S. Contralateral thalamic perfusion in patients with reflex sympathetic dystrophy syndrome. Lancet 1999; 354: 1790–91. Talairach J, Tournoux P. Co-planar Stereotaxic Atlas of the Human Brain. Stuttgart: Thieme, 1988. Friston KJ, Holmes AP, Worsley KJ, Poline JB, Frith CD, Frackowiak RSJ. Statistical parametric maps in functional imaging: a general approach. Hum Brain Mapping 1995; 2: 189–210.
THE LANCET • Vol 355 • February 5, 2000
CORRESPONDENCE 4
5
Otte A, Mueller-Brand J, Fierz L. Brain SPECT findings in late whiplash syndrome. Lancet 1995; 345: 1513–14. Roelcke U, Curt A, Otte A, Missimer J, Maguire JP, Dietz V, Leenders KL. Influence of spinal cord injury on cerebral sensorimotor systems: a PET study. J Neurol Neurosurg Psychiatry 1997; 62: 61–65.
Sir—The increased thalamic perfusion detected by SPECT imaging described by Fukumoto and co-workers1 is an interesting observation but we doubt it sheds light on the pathogenesis of reflex sympathetic dystrophy syndrome (RSDS). An increase in thalamic perfusion simply indicates increased metabolic activity, which in turn reflects the extra sensory input from continuous pain stimuli, and this decreases over time as an adaptive response. Unfortunately, the investigators used healthy individuals as controls, but a control group of patients with other types of acute pain in the limbs would have created a far more relevant set of results. The cause and pathology of RSDS remains controversial.2 It is seen after minor injuries and is often associated and prolonged by medico-legal litigation. An identical condition can be seen in holy men in India who as a sign of their faith, hold up one arm in perpetuity. After some years, the limb shows the signs of RSDS—shiny hairless fragile skin and trophic changes in the nails. Immobilisation for any reason, from hemiplegia to choice, seems to result in this phenomenon. High-tech evaluations of the brain simply map activity and should not be interpreted as reflecting underlying pathogenesis. John W Norris, Alan West Sunnybrook & Women’s College Health Sciences Centre, University of Toronto Clinic, Toronto, Ontario M4N 3M5, Canada (e-mail: [email protected]) 1
2
Fukumoto M, Ushida T, Zinchuk VS, Yamamoto Y, Yoshida S. Contralateral thalamic perfusion in patients with reflex sympathetic dystrophy syndrome. Lancet 1999; 354: 1790–91. Wasner G, Backonja M-M, Baron R. Traumatic neuralgias. In: Backonja M-M, ed. Neurologic clinics. Philadelphia: WB Saunders, 1998: 851–68.
Authors’ reply Sir—Emma Chojnowska attracts our attention to the terminology used to characterise the complex regional pain syndrome (CRPS). Indeed, reflex sympathetic dystrophy syndrome (RSDS) is a CRPS, because it is a pain syndrome that does not involve the damage of nerves. Causalgia, on the other hand, does involve nerve damage. In our study, we followed this classification strictly and excluded
THE LANCET • Vol 355 • February 5, 2000
patients with a history of damaged nerves. Therefore, the study was focused on pure RSDS patients. Chojnowska says that no correlation should be expected between variations of thalamic perfusion and sympathetic instability found in patients with RSDS. To clinicians dealing with patients with CRPS this assumption is an over simplification. Both types of CRPS do show signs of sympathetic instability. Chojnowska cites two papers that reported changes in thalamic perfusion in patients with peripheral neuropathies and central post-stroke pain.1,2 The study by Iadarola and colleagues1 showed decrease in contralateral thalamic perfusion in patients with chronic neuropathic pain for more than 2 years, and their findings are comparable with our findings from the group of patients with a long-term RSDS. The results of the study by Cesaro and colleagues2 cannot serve as an appropriate comparison with ours because patients analysed by Cesaro’s group had had a cerebral vascular accident. The paper by Di Piero and colleages,3 which was cited by Chojnowska should be interpreted carefully because functional imaging of the brain for unilateral peripheral pain due to metastatic cancer was analysed. Because computed tomography scan was used to assess the state of the brain, the possibility that non-detected microscopic foci of metastatic dissemination contributed to the chronic pain described in this study cannot be ruled out. Undoubtedly, testing our results in a larger group and re-evaluation of the data with Statistical Parametric Mapping (SPM), as suggested by Andreas Otte, would be useful both for better understanding of the essence of reported data and optional functional neuroimaging. While re-evaluation of the findings by SPM does not represent any difficulties, testing them in a larger patient group is much more complicated. It is very difficult to find a large number of patients who have RSDS, but who do not have neurological and psychiatric dysfunction. We believe that studying the pathogenesis of noxious input from the periphery will prove to be important to our understanding of the mechanisms of brain plasticity. In patients with RSDS, the evaluation of the state of glucose metabolism may provide clues to a better understanding of this disorder. John Norris and Alan West suggest that the best possible controls for a
study of the pathogenesis of RSDS would be patients with acute pain in the limbs. Such controls would enable the direct comparison of thalamic perfusion in patients RSDS and those without RSDS. We expect that in the acute phase of RSDS, thalamic perfusion will probably be increased and will then gradually decrease to levels similar to those before the injury. However, such controls have their own limitations, including incomparable types of traumatic injury, different extents of injury, and the fact that the patients with acute traumatic pain may not be able to undergo single photon emission computed tomography at the peak of pain, when the most valuable information about the state of thalamic perfusion is expected. Therefore, the data obtained from such controls, while obviously useful, will probably still require another control group for comparison. *Mitsutaka Fukumoto, Takahiro Ushida, Vadim S Zinchuk, Hiroshi Yamamoto, Shoji Yoshida Departments of *Radiology, Orthopaedics, and Anatomy and Cell Biology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan (e-mail: [email protected]) 1
2
3
Iadarola NJ, Max MB, Berman KF, et al. Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain. Pain 1995; 63: 55–64. Cesaro P, Mann MW, Moretti JL, et al. Central pain and thalamic hyperactivity: a single photon emission computerised tomographic study. Pain 1991; 47: 329–36. Di Piero V, Jones AKP, Iannotti F, et al. Chronic pain: a PET study of the central affected of percutaneous high cervical cordotomy. Pain 1991; 46: 9–12.
Prevalence of multiple system atrophy Sir—A Shrag and colleagues (Nov 20, p 1771)1 report the prevalence of multiple system atrophy (MSA) and progressive supranuclear palsy. MSA is a sporadic neurodegenerative disease that produces a variable combination of dopa-unresponsive Parkinson’s disease, autonomic failure, and cerebellar and pyramidal signs. The epidemiology of such a rare and severe disease is challenging: necropsy studies are biased towards atypical cases of Parkinson’s disease that may overestimate the frequency of MSA, and population-based studies are limited by the low number of cases detected. Shrag and colleagues detected two possible and two probable cases of MSA through the computerised records of 12 general practices (population at risk 121 608). Moreover, three of 1190
495