B. Neundörfer

OBJECTIVE: To use magnetoencephalography to assess possible cortical reorganization in the primary somatosensory cortex (S1) of patients with complex regional pain syndrome (CRPS). BACKGROUND: Patterns of pain and sensory symptoms in CRPS may indicate plastic changes of the CNS. METHODS: Magnetic source imaging was used to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 12 patients. RESULTS: The authors found a significant shrinkage of the extension of the cortical hand representation for the CRPS affected side. The center of the hand was shifted toward the cortical representation of the lip. The cortical reorganization correlated with the amount of CRPS pain (r = 0.792), as measured by the McGill questionnaire, and the extent of mechanical hyperalgesia (r = 0.860). Using multiple regression analysis, the best predictor for the plastic changes was found to be mechanical hyperalgesia. Additionally, S1 sources following tactile stimulation were significantly increased on the CRPS side compared to the unaffected limb. CONCLUSIONS: This study showed reorganization of the S1 cortex contralateral to the CRPS affected side. The reorganization appeared to be linked to complaints of neuropathic pain.

OBJECTIVE: To characterize reorganization of the primary somatosensory cortex (S1) during healing process in complex regional pain syndrome (CRPS). BACKGROUND: Recently, the authors showed extensive reorganization of the S1 cortex contralateral to the CRPS affected side. Predictors for these plastic changes were CRPS pain and the extent of mechanical hyperalgesia. It is unclear how these S1 changes develop following successful therapy. METHODS: The authors used magnetic source imaging to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 10 patients during a year or more of follow-up. RESULTS: Cortical reorganization reversed coincident with clinical improvement. A reduction of CRPS pain correlated with recovery from cortical reorganization. CONCLUSIONS: Changes of the somatotopic map within the S1 cortex may depend on CRPS pain and its recovery.

Early diagnosis is a prerequisite for a successful treatment of complex regional pain syndrome (CRPS). In order to describe neurological symptoms which characterize CRPS, we evaluated 145 patients prospectively. Two-thirds of these were women, the mean age at time of investigation was 50.4 years. CRPS followed limb trauma, surgery and nerve lesion. Employing the current IASP criteria 122 patients were classified as CRPS I and 23 as CRPS II. All patients were assessed clinically pain was quantified using the McGill pain questionnaire, skin temperature was measured by an infrared thermometer and a subgroup of 57 patients was retested in order to determine thermal thresholds (QST). Of our patients 42% reported stressful life events in a close relationship to the onset of CRPS and 41% had a history of chronic pain before CRPS. The latter group of patients gave a higher rating of CRPS pain (P<0.05). The major symptoms were pain at rest in 77% and hyperalgesia in 94%. Typical pain was deep in the limb having a tearing character. Patients getting physical therapy had significantly less pain than those without (P<0.04). Autonomic signs were frequent (98%) and often changed with the duration of CRPS. Skin temperature was warmer in acute and colder in chronic stages (P<0.001). Likewise edema had a higher incidence in acute stages (P<0.001). We found no correlation between pain and autonomic dysfunction. Motor dysfunction (present in 97%) included weakness, tremor, exaggerated tendon reflexes, dystonia or myoclonic jerks. QST revealed increased warm perception thresholds (P<0.02) and decreased cold pain thresholds (P<0.03) of the affected limb. The detailed knowledge of clinical features of CRPS could help physicians early to recognize the disease and thus to improve therapy outcome.

Molecular events that result in loss of pain perception are poorly understood in diabetic neuropathy. Our results show that the receptor for advanced glycation end products (RAGE), a receptor associated with sustained NF-kappaB activation in the diabetic microenvironment, has a central role in sensory neuronal dysfunction. In sural nerve biopsies, ligands of RAGE, the receptor itself, activated NF-kappaBp65, and IL-6 colocalized in the microvasculature of patients with diabetic neuropathy. Activation of NF-kappaB and NF-kappaB-dependent gene expression was upregulated in peripheral nerves of diabetic mice, induced by advanced glycation end products, and prevented by RAGE blockade. NF-kappaB activation was blunted in RAGE-null (RAGE(-/-)) mice compared with robust enhancement in strain-matched controls, even 6 months after diabetes induction. Loss of pain perception, indicative of long-standing diabetic neuropathy, was reversed in WT mice treated with soluble RAGE. Most importantly, loss of pain perception was largely prevented in RAGE(-/-) mice, although they were not protected from diabetes-induced loss of PGP9.5-positive plantar nerve fibers. These data demonstrate, for the first time to our knowledge, that the RAGE-NF-kappaB axis operates in diabetic neuropathy, by mediating functional sensory deficits, and that its inhibition may provide new therapeutic approaches.

BACKGROUND AND PURPOSE: The number of stroke patients and the healthcare costs of strokes are expected to rise. The objective of this study was to determine the direct costs of first ischemic stroke and to estimate the expected increase in costs in Germany. METHODS: An incidence-based, bottom-up, direct-cost-of-ischemic-stroke study from the third-party payer's perspective was performed, incorporating 10-year survival data and 5-year resource use data from the Erlangen Stroke Registry. Discounted lifetime year 2004 costs per case were obtained and applied to the expected age and sex evolution of the German resident population in the period 2006 to 2025. RESULTS: The overall cost per first-year survivor of first-ever ischemic stroke was estimated to be 18,517 euros (EUR). Rehabilitation accounted for 37% of this cost, whereas in subsequent years outpatient care was the major cost driver. Discounted lifetime cost per case was 43,129 EUR overall and was higher in men (45,549 EUR) than in women (41,304 EUR). National projections for the period 2006 to 2025 showed 1.5 million and 1.9 million new cases of ischemic stroke in men and women, respectively, at a present value of 51.5 and 57.1 billion EUR, respectively. CONCLUSIONS: The number of stroke patients and the healthcare costs of strokes in Germany will rise continuously until the year 2025. Therefore, stroke prevention and reduction of stroke-related disability should be made priorities in health planning policies.