Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models.

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous disorder. All mendelian patterns of inheritance have been described. We identified a homozygous p.A335V mutation in the MED25 gene in an extended Costa Rican family with autosomal recessively inherited Charcot-Marie-Tooth neuropathy linked to the CMT2B2 locus in chromosome 19q13.3. MED25, also known as ARC92 and ACID1, is a subunit of the human activator-recruited cofactor (ARC), a family of large transcriptional coactivator complexes related to the yeast Mediator. MED25 was identified by virtue of functional association with the activator domains of multiple cellular and viral transcriptional activators. Its exact physiological function in transcriptional regulation remains obscure. The CMT2B2-associated missense amino acid substitution p.A335V is located in a proline-rich region with high affinity for SH3 domains of the Abelson type. The mutation causes a decrease in binding specificity leading to the recognition of a broader range of SH3 domain proteins. Furthermore, Med25 is coordinately expressed with Pmp22 gene dosage and expression in transgenic mice and rats. These results suggest a potential role of this protein in the molecular etiology of CMT2B2 and suggest a potential, more general role of MED25 in gene dosage sensitive peripheral neuropathy pathogenesis.

Loss of pain perception in diabetes is dependent on a receptor of the immunoglobulin superfamily.

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.

Treating dopamimetic psychosis in Parkinson's disease: structured review and meta-analysis.

Psychosis due to dopamimetic treatment is a difficult problem in patients with Parkinson's disease (PD). The aim of this structured review with meta-analysis was to evaluate which neuroleptic drugs can efficiently be used to treat drug-induced psychosis (DIP) in Parkinson's disease. Electronic databases were screened for the key words Parkinson's disease and psychosis. Only 7 trials with a satisfactory allocation concealment and data reporting were included into the study. Two trials compared low-dose clozapine versus placebo with a significantly better outcome for clozapine regarding efficacy and motor functioning. In one trial clozapine was compared against quetiapine showing equivalent efficacy and tolerability. However, in two placebo controlled trials quetiapine failed to show efficacy. In two further placebo controlled trials olanzapine did not improve psychotic symptoms and significantly caused more extrapyramidal side effects. Based on randomized trial-derived evidence which is currently available, only clozapine can be fully recommended for the treatment of DIP in PD. Olanzapine should not be used in this indication.

Activation of the RAGE pathway: a general mechanism in the pathogenesis of polyneuropathies?

OBJECTIVES: Binding of ligands to the receptor for advanced glycation end products (RAGE) results in activation of the transcription factor NF-kappaB and subsequent expression of NF-kappaB regulated cytokines and is a possible pathomechanism in diabetic and in vasculitic polyneuropathies (PNP). We wanted to investigate whether the newly discovered RAGE pathway also contributes to the pathogenesis of various other PNP. METHODS: The presence of the RAGE ligand Nepsilon-Carboxymethyllysine (CML), the receptor itself and NF-kappaBp65 was studied in sural nerve biopsies of patients with alcohol-associated PNP (n=5), PNP owing to vitamin B12 deficiency (n=5), chronic inflammatory demyelinating PNP (CIDP, n=10), Charcot-Marie-Tooth disease (CMT) I or II (n= 10), PNP caused by monoclonal gammopathy of unknown significance (MGUS) (n=5), idiopathic PNP (n=10) and five normal controls by immunohistochemistry. Biopsies of either ten patients with diabetic and vasculitic PNP served as positive controls. RESULTS: CML, RAGE and NF-kappaBp65 were found in co-localization in epineurial vessels in PNP owing to vitamin B12 deficiency, diabetes and vasculitis and in the perineurium in diabetic PNP, vasculitic PNP and in some cases in CIDP and vitamin B12 deficiency. Only diabetic subjects demonstrated co-expression of the three antigens in endoneurial vessels. Increased CML, RAGE and NF-kappaBp65 expression was detected in endoneurial and epineurial mononuclear cells in CIDP and in vasculitic PNP. Additionally, RAGE expression in Schwann cells was significantly increased in diabetic PNP. DISCUSSION: These data suggest that activation of the RAGE pathway might contribute to the pathogenesis of CIDP, PNP owing to vitamin B12 deficiency, diabetes and vasculitis, whereas it does not seem to be involved in the pathogenesis of PNP owing to alcohol, MGUS, CMT I or II and idiopathic PNP.

Lifetime cost of ischemic stroke in Germany: results and national projections from a population-based stroke registry: the Erlangen Stroke Project.

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.

Mislocalization of tactile stimulation in patients with complex regional pain syndrome.

Complex-Regional-Pain-Syndromes (CRPS) are characterized by sensory,motor and autonomic dysfunctions. Patterns of sensory symptoms suggest changes within the central nervous system (CNS). Recently, we could show substantial reorganization of somatotopic maps within the central nervous system of patients with CRPS using functional imaging techniques (Maihofner et al. Neurology, 2003). These changes were predicted by CRPS pain and mechanical hyperalgesia. In the present study we looked for potential psychophysical correlates of cortical reorganization in CRPS. Sequential pneumatic non-noxious tactile stimulation was performed at digits 1 and 5 in 24 patients with CRPS of the upper extremities. Both the unaffected and affected side were examined. Patients were interviewed for tactile induced sensations. The occurrence of mislocalizations was correlated with a detailed psychophysical examination in which sensory, motor and autonomic symptoms were assessed. Eight patients (30 %) reported tactile mislocalizations, which were felt in the affected hand. In four cases the referred sensations spread into other nerve territories (ulnar/median nerve). Presence of mechanical hyperalgesia significantly predicted the occurrence of mislocalizations. In contrast, in a healthy control group, no mislocalizations were found. Thus, our results further support the concept of pain-induced reorganization in the somatosensory system of CRPS patients.

First aid in acute stroke : introducing a concept of first action to laypersons.

OBJECTIVE: First aid training is well established to teach the public how to recognize a medical emergency and take appropriate action. Though it is now handled as a high priority emergency stroke is not among the main topics of first aid. We investigated if first aid training may be useful for enhancing stroke awareness. METHODS: We developed a 15-20 minute teaching session about stroke as an emergency including signs and symptoms and first hands-on measures. The session was integrated in standard first aid training of the St John Ambulance of Germany and participants were asked to fill out a questionnaire regarding their knowledge about stroke. Subjects were questioned before the stroke lesson and again at the end of the training. RESULTS: 532 participants of the training responded to the questionnaire (mean age 28.6 years, 53.6% male). There was a significant increase in proportion of subjects correctly defining what stroke is (28.4% vs. 69.9%, p < 0,001) and in the mean number of stroke symptoms listed (1.52 vs. 3.35, p < 0,001) by the participants. The number of participants unable to list at least 1 symptom decreased significantly (12.8 vs. 3.6%, p<0.001). CONCLUSIONS: In our study a teaching lesson integrated in first aid training was effective in improving stroke knowledge of participants. First aid training should be used for stroke information complementary to other activities like mass media campaigns as it is effective, could reach younger people that are not primarily interested in stroke and provides connections to other health topics.

Intravascular lymphomatosis mimicking disseminated encephalomyelitis and encephalomyelopathy.

Intravascular lymphomatosis is characterized by the presence of large lymphoma cells predominantly within small vessels. This report presents two patients with diagnostically misleading neurological manifestation of this disease. Case 1, a 63-year-old man, developed a sensorimotor transverse spinal cord syndrome and encephalopathy. Lumbar puncture revealed albuminocytological dissociation. Magnetic resonance imaging (MRI) showed progression of multifocal infarct-like lesions in the brain, the thoracic cord and the medullary cone. Autoimmune inflammation was suspected, and the patient received immunosuppressive therapy with immunoglobulins, steroids and azathioprine. He died 18 months after the onset of symptoms. Case 2, a 68-year-old man, showed fluctuating aphasia, disorientation, and fever for several months. Brain MRI-scan, electroencephalography (EEG) and cerebrospinal fluid (CSF) cytology were inconclusive. Premortal biopsy of lesions in liver and right suprarenal gland showed no further characterized malignancy. He died 6 months after the first occurrence of symptoms. Autopsy of both cases revealed an intravascular lymphomatosis. Tumour cells were seen disseminated in extranodal sites including heart, lung, adrenal gland, spleen, thyroid gland and brain. An intravascular lymphomatosis should be considered when a meningoencephalitic symptomatology is unclear. A biopsy of different organs including the brain and leptomeninges should not be delayed to ensure ante mortem diagnosis and to initiate chemotherapy.

Transient tetraplegia after cervical facet joint injection for chronic neck pain administered without imaging guidance.

We report about a patient in whom transient tetraplegia with intact proprioception occurred immediately after infiltration of a facet joint at the C6 level guided by anatomical landmarks. After positioning the patient supine and applying atropine and oxygen, respiration and circulation were stable and all symptoms resolved within the next 30 min. The type of neurological pattern and the course of disease suggest an inadvertent injection into a cervical radicular artery that reinforces the anterior spinal artery. This complication is potentially serious and may be permanently disabling or life threatening. It should be considered by any clinician performing "blind" zygapophysial joint injections in the cervical spine. Using imaging guidance should help prevent this type of complication.

Taste disorders in acute stroke: a prospective observational study on taste disorders in 102 stroke patients.

BACKGROUND AND PURPOSE: The aim of the study was to assess whether and how frequently patients with acute first-ever stroke exhibit gustatory dysfunction. METHODS: We performed a 1-year prospective observational study. Gustatory function was assessed using the standardized "taste strips" test. In addition, we assessed olfactory function, swallowing, stroke location, comorbidities, and the patients' medication. RESULTS: A total of 102 consecutive patients were enrolled (45 female, 57 male; mean age, 63 years); 31 of them (30%) exhibited gustatory loss and 7 (6%) had lateralized impairment of taste function. Predictors of impaired taste function were male gender (P=0.003), high National Institutes of Health Stroke Scale (NIHSS) score at admission (P=0.009), coexisting swallowing dysfunction (P=0.026), and a stroke of partial anterior circulation subtype (PACS) (P=0.008). In particular, in hypogeusic patients the lesion was most frequently localized in the frontal lobe (P=0.009). Follow-up examinations in 14 patients indicated improvement of taste sensitivity. CONCLUSIONS: Taste disorders after stroke are frequent. A significant association was found for male gender, high NIHSS score, swallowing disorder, and PACS, particularly in the frontal lobe. Generally, taste disorders after stroke seem to have a good prognosis.

Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study.

Complex Regional Pain Syndromes (CRPS) are characterized by a triad of sensory, motor and autonomic dysfunctions of still unknown origin. Pain and mechanical hyperalgesia are hallmarks of CRPS. There are several lines of evidence that central nervous system (CNS) changes are crucial for the development and maintenance of mechanical hyperalgesia. However, little is known about the cortical structures associated with the processing of hyperalgesia in pain patients. This study describes the use of functional magnetic resonance imaging (fMRI) to delineate brain activations during pin-prick hyperalgesia in CRPS. Twelve patients, in whom previous quantitative sensory testing revealed the presence of hyperalgesia to punctuate mechanical stimuli (i.e. pin-prick hyperalgesia), were included in the study. Pin-prick-hyperalgesia was elicited by von-Frey filaments at the affected limb. For control, the identical stimulation was performed on the unaffected limb. fMRI was used to explore the corresponding cortical activations. Mechanical stimulation at the unaffected limb was non-painful and mainly led to an activation of the contralateral primary somatosensory cortex (S1), insula and bilateral secondary somatosensory cortices (S2). The stimulation of the affected limb was painful (mechanical hyperalgesia) and led to a significantly increased activation of the S1 cortex (contralateral), S2 (bilateral), insula (bilateral), associative-somatosensory cortices (contralateral), frontal cortices and parts of the anterior cingulate cortex. The results of our study indicate a complex cortical network activated during pin-prick hyperalgesia in CRPS. The underlying neuronal matrix comprises areas not only involved in nociceptive, but also in cognitive and motor processing.

Persistent idiopathic facial pain exists independent of somatosensory input from the painful region: findings from quantitative sensory functions and somatotopy of the primary somatosensory cortex.

In 14 patients with unilateral persistent idiopathic facial pain (PIFP), classified according to the criteria of the International Headache Society, and 16 age-matched control subjects sensory functions were examined on the face by quantitative sensory testing (QST). Additionally, the somatotopy of the primary somatosensory cortex (SI) to tactile input from the pain area was evaluated by means of magnetoencephalography. Previously reported abnormalities in PIFP as a dishabituation of the R2 component of the blink reflex and psychiatric disturbances were co-evaluated. Psychiatric evaluation included a Structured Clinical Interview for axis-I DSM IV disorders (SCID-I) and employment of the SCL-90-R and a depression scale (ADS). Thresholds to touch, pin prick, warm, cold, heat and pressure pain as well as the pain ratings to single and repetitive (perceptual wind up) painful pin prick stimuli did not indicate a significant sensory deficit or hyperactivity in the pain area when compared with the asymptomatic side nor when compared with the values of healthy control subjects. QST results were not significantly altered in patients (n=4) that showed an abnormal dishabituation of the R2 component of the blink reflex. The interhemispheric difference in distance between the cortical representation of the lip and the index finger did not differ between patients and control subjects. Psychiatric evaluation did not disclose significant abnormalities at a group level. It is concluded that PIFP is maintained by mechanisms which do not involve somatosensory processing of stimuli from the pain area.

Hyperexcitability of the primary somatosensory cortex in migraine--a magnetoencephalographic study.

The excitability of the cerebral cortex in the interictal state of migraine appears to be fundamental in the brain's susceptibility to migraine attacks. Subpopulations of cortical neurons are reported to have different physiological response properties to different interstimulus intervals (ISIs) and, hence, may be differentially altered or modulated in migraine. The aim of this study therefore was to evaluate response characteristics of temporally and spatially defined neuronal subpopulations in the cortex of migraineurs. To this end, we measured, by means of magnetoencephalography (37-channel neuromagnetometer), the response properties of the early components of the somatosensory evoked magnetic fields following electrical stimulation of the median nerve, the N20m and P35m, at ISIs ranging between 0.3 and 6 s. As a measure of the number of excited neurons underlying the N20m and P35m, we evaluated the root mean square (r.m.s.) of the deflections across all 37 channels at the corresponding latencies and the corresponding dipole moment of the equivalent current dipole (ECD strength). Twenty consecutive women with at least three migraine attacks/month (range 3-8/month) fulfilling the International Headache Society criteria and 20 age-matched healthy women were included in the study. In migraineurs, the r.m.s. and ECD strength of N20m was increased at all ISIs (r.m.s., P < 0.05; ECD strength, P < 0.01) and positively related to the mean attack frequency (r.m.s., R(s) = 0.6, P < 0.01; ECD strength, R(s) = 0.5, P < 0.05). In contrast, the r.m.s. and ECD strength of P35m did not differ significantly between migraineurs and control subjects and did not correlate significantly with the frequency of migraine attacks. Responses to different ISIs did not differ significantly between migraineurs and control subjects. The r.m.s. of N20m was stable for ISIs between 0.5 and 6 s and decreased significantly at an ISI of 0.3 s. In contrast, the r.m.s. of P35m decreased continuously as the ISI was decreased below 6 s and this reached significance for an ISI of < or =1 s. Habituation of N20m or P35m, i.e. a decrease in response magnitude following repetitive stimulation over time, was not found in either the control subjects or in the migraineurs. It is concluded that the population of neurons in the primary somatosensory cortex underlying the N20m are hyperexcitable and that this hyperexcitability is linked to the frequency of migraine attacks. This hyperexcitability appears not to be related to habituation since habituation was not found in the control subjects. In contrast, the magnitude of P35m is not pathophysiologically linked to the interictal state of migraine. Furthermore, the cellular mechanisms causing ISI-dependent depression of N20m and P35m are not altered in migraine.

Emergency calls in acute stroke.

BACKGROUND AND PURPOSE: In the last 10 years, stroke has become a medical emergency. Subsequently, early recognition of stroke symptoms and rapid activation of the medical system are essential. We sought to investigate what witnesses or victims of an acute stroke syndrome recognize and report in the actual situation. METHODS: We analyzed the recordings of all patients admitted to our stroke unit via the Emergency Medical System (EMS) dispatch center in Nuremberg within 1 year. With a structured evaluation form, the calls were screened for symptoms reported and for any diagnosis or other facts mentioned spontaneously or in response to a question by the dispatcher. We also evaluated data about EMS response and patient condition on admission. RESULTS: Of 482 patients treated in our stroke unit, 141 calls were evaluated. Main symptoms reported included speech problems (25.5%), motor deficits (21.9%), and disturbances of consciousness (14.8%). In many cases, a fall (21.2%) was presented as the main problem. Sensory deficits (7.8%) and vertigo (5.6%) were rarely mentioned. In 28 calls (19.8%), stroke was mentioned as a possible cause of the acute health problems. The dispatcher suspected a stroke in 51.7% of all cases. CONCLUSIONS: This is one of the first studies to investigate emergency calls in acute stroke. We found that motor deficits and speech problems were the most dramatic symptoms that led to activation of the EMS. Other symptoms were less frequently reported, or atypical descriptions were given. Educational efforts are needed to improve recognition of atypical stroke symptoms by stroke victims and EMS professionals.

Telemedicine in emergency evaluation of acute stroke: interrater agreement in remote video examination with a novel multimedia system.

BACKGROUND AND PURPOSE: In acute stroke care, rapid but careful evaluation of patients is mandatory but requires an experienced stroke neurologist. Telemedicine offers the possibility of bringing such expertise quickly to more patients. This study tested for the first time whether remote video examination is feasible and reliable when applied in emergency stroke care using the National Institutes of Health Stroke Scale (NIHSS). METHODS: We used a novel multimedia telesupport system for transfer of real-time video sequences and audio data. The remote examiner could direct the set-top camera and zoom from distant overviews to close-ups from the personal computer in his office. Acute stroke patients admitted to our stroke unit were examined on admission in the emergency room. Standardized examination was performed by use of the NIHSS (German version) via telemedicine and compared with bedside application. RESULTS: In this pilot study, 41 patients were examined. Total examination time was 11.4 minutes on average (range, 8 to 18 minutes). None of the examinations had to be stopped or interrupted for technical reasons, although minor problems (brightness, audio quality) with influence on the examination process occurred in 2 sessions. Unweighted kappa coefficients ranged from 0.44 to 0.89; weighted kappa coefficients, from 0.85 to 0.99. CONCLUSIONS: Remote examination of acute stroke patients with a computer-based telesupport system is feasible and reliable when applied in the emergency room; interrater agreement was good to excellent in all items. For more widespread use, some problems that emerge from details like brightness, optimal camera position, and audio quality should be solved.

Temporo-spatial analysis of cortical activation by phasic innocuous and noxious cold stimuli--a magnetoencephalographic study.

Clinical findings and recent non-invasive functional imaging studies pinpoint the insular cortex as the crucial brain area involved in cold sensation. By contrast, the role of primary (SI) and secondary (SII) somatosensory cortices in central processing of cold is controversial. So far, temporal activation patterns of cortical areas involved in cold processing have not been examined. Using magnetoencephalography, we studied, in seven healthy subjects, the temporo-spatial dynamics of brain processes evoked by innocuous and noxious cold stimulation as compared to tactile stimuli. For this purpose, a newly designed and magnetically silent cold-stimulator was employed. In separate runs, cold and painful cold stimuli were delivered to the dorsum of the right hand. Tactile afferents were stimulated by pneumatic tactile stimulation.Following innocuous cold stimulation (DeltaT=5+/-0.3 degrees C in 50+/-2ms), magnetic source imaging revealed an exclusive activation of the contra- and ipsilateral posterior insular cortex. The mean peak latencies were 194.3+/-38.1 and 241.0+/-31.7ms for the response in the ipsi- and contralateral insular cortex, respectively. Based on the measurement of onset latencies, the estimated conduction velocity of peripheral nerve fibres mediating cold fell in the range of Adelta-fibres (7.4+/-0.8 m/s). Noxious cold stimulation (DeltaT=35+/-5 degrees C in 70+/-12ms) initially activated the contra- and ipsilateral insular cortices in the same latency ranges as innocuous cold stimuli. Additionally, we found an activation of the contra- and ipsilateral SII areas (peak latencies 304+/-22.7 and 310.1+/-19.4ms, respectively) and a variable activation of the cingulate cortex. Notably, neither cold- nor painful cold stimulation produced an activation of SI. By contrast, the evoked cortical responses following tactile stimulation could be located to the contralateral SI cortex and bilateral SII. In conclusion, this study strongly corroborates the posterior insular cortex as the primary somatosensory area for cortical processing of cold sensation. Furthermore, it supports the role of SII and the cingulate cortex in mediating freeze-pain. Therefore, these results suggest different processing of cold, freeze-pain and touch in the human brain.

Sympathetic vasoconstrictor reflex pattern in patients with complex regional pain syndrome.

Twenty patients suffering from complex regional pain syndrome (CRPS) and 21 healthy control subjects were examined to evaluate sympathetic reflex vasoconstriction. The mean age of the 12 female and eight male patients was 48.9 (21-72) years. At the time of investigation the median duration of the disease was 8.5 weeks (2-70). Twenty-one healthy subjects were investigated for control. Different maneuvers, such as the veno-arteriolar reflex (VAR), inspiratory gasp (IG), cold pressor test (CP) and mental arithmetic (MA), were employed to induce vasoconstriction while the cutaneous blood flow of the affected and the contralateral limb was recorded. In addition, the skin temperature of both limbs was measured by infrared thermography. In 14 of 20 patients and in 14 of 21 control subjects vasoconstriction due to the provocation tests could be measured, while the remaining six patients and seven controls showed vasodilatation in at least one test, and by that they were excluded from analysis of vasoconstrictor reflex pattern. After thermoregulatory adaptation skin temperature was not different between the affected and the unaffected limb. Sympathetic reflex vasoconstriction triggered by MA which represents cortical generated, moderate vasoconstrictor stimulus, was significantly reduced on the affected limb (102.9% of prestimulus period) when compared to the control limb (85.0%, P < 0.002) or to controls (84.8%, P < 0.001). VAR (pure postganglionic), IG and CP (both spinal and supraspinal), representing stronger vasoconstrictor stimuli, revealed no significant side to side difference of sympathetic vasoconstriction and no significant difference as compared to controls. In conclusion our findings prove impairment of sympathetic vasoconstrictor activity after central vasoconstrictor stimulation in CRPS, and possible mechanisms are discussed.