Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by sensory, motor, and autonomic symptoms. It develops after limb trauma and may be associated with relevant ...psychiatric comorbidity. As there is evidence for central pathophysiology which might be related to an altered opioidergic neurotransmission, we investigated the cerebral opioid receptor status under resting conditions in this patient population.
In this case-control study, 10 patients with CRPS and 10 age- and gender-matched healthy subjects underwent a PET scan using the subtype-nonselective opioidergic radioligand (18)Ffluoroethyl-diprenorphine. As a surrogate for regional cerebral opioid receptor availability, the opioid receptor binding potential (OR-BP) was assessed by means of the modified Logan plot with reference region input for categorical group comparison and correlation with clinical data in the patient group.
Patients with CRPS showed reduced OR-BP in contralateral amygdala and parahippocampal gyri and increased OR-BP in contralateral prefrontal cortical areas. When OR-BP in the midcingulate cortex and the ipsilateral temporal cortex was low, the McGill pain rating index was high. In general, when anxiety and depression scales were high, contralateral temporal OR-BP was high as well. In addition, the anxiety scale decreased with increasing OR-BP in the contralateral parahippocampal cortex.
These results demonstrate altered central opioidergic neurotransmission in CRPS. The correlation of regional opioid receptor availability to measures of pain, anxiety, and depression underlines the clinical importance of these findings.
Approximately 3.2%-6% of the general population harbor an unruptured intracranial aneurysm (UIA). Ruptured aneurysms represent a significant healthcare burden, and preventing rupture relies on early ...detection and treatment. Most patients with UIAs are asymptomatic, and many of the symptoms associated with UIAs are nonspecific, which makes diagnosis challenging. This study explored symptoms associated with UIAs, the rate of resolution of such symptoms after microsurgical treatment, and the likely pathophysiology.
A retrospective review of patients with UIAs who underwent microsurgical treatment from January 1, 2014, to December 31, 2020, at a single quaternary center were identified. Analyses included the prevalence of nonspecific symptoms upon clinical presentation and postoperative follow-up; comparisons of symptomatology by aneurysmal location; and comparisons of patient demographics, aneurysmal characteristics, and poor neurologic outcome at postoperative follow-up stratified by symptomatic versus asymptomatic presentation.
The analysis included 454 patients; 350 (77%) were symptomatic. The most common presenting symptom among all 454 patients was headache (
= 211 46%), followed by vertigo (
= 94 21%), cognitive disturbance (
= 6815%), and visual disturbance (
= 64 14%). Among 328 patients assessed for postoperative symptoms, 258 (79%) experienced symptom resolution or improvement.
This cohort demonstrates that the clinical presentation of patients with UIAs can be associated with vague and nonspecific symptoms. Early detection is crucial to prevent aneurysmal subarachnoid hemorrhage. It is imperative that physicians not rule out aneurysms in the setting of nonspecific neurologic symptoms.
: Patients with supratentorial cavernous malformations (SCMs) commonly present with seizures. First-line treatments for cavernoma-related epilepsy (CRE) include conservative management (antiepileptic ...drugs (AEDs)) and surgery. We compared seizure outcomes of CRE patients after early (≤6 months) vs. delayed (>6 months) surgery.
: We compared outcomes of CRE patients with SCMs surgically treated at our large-volume cerebrovascular center (1 January 2010-31 July 2020). Patients with 1 sporadic SCM and ≥1-year follow-up were included. Primary outcomes were International League Against Epilepsy (ILAE) class 1 seizure freedom and AED independence.
: Of 63 CRE patients (26 women, 37 men; mean ± SD age, 36.1 ± 14.6 years), 48 (76%) vs. 15 (24%) underwent early (mean ± SD, 2.1 ± 1.7 months) vs. delayed (mean ± SD, 6.2 ± 7.1 years) surgery. Most (32 (67%)) with early surgery presented after 1 seizure; all with delayed surgery had ≥2 seizures. Seven (47%) with delayed surgery had drug-resistant epilepsy. At follow-up (mean ± SD, 5.4 ± 3.3 years), CRE patients with early surgery were more likely to have ILAE class 1 seizure freedom and AED independence than those with delayed surgery (92% (44/48) vs. 53% (8/15),
= 0.002; and 65% (31/48) vs. 33% (5/15),
= 0.03, respectively).
: Early CRE surgery demonstrated better seizure outcomes than delayed surgery. Multicenter prospective studies are needed to validate these findings.
Racial and socioeconomic health disparities are well documented in the literature. This study examined patient demographics, including socioeconomic status (SES), among individuals presenting with ...aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (UIA) to identify factors associated with aSAH presentation. A retrospective assessment was conducted of all patients with aSAH and UIA who presented to a large-volume cerebrovascular center and underwent microsurgical treatment from January 2014 through July 2019. Race and ethnicity, insurance type, and SES data were collected for each patient. Comparative analysis of the aSAH and UIA groups was conducted. Logistic regression models were also employed to predict the likelihood of aSAH presentation based on demographic and socioeconomic factors. A total of 640 patients were included (aSAH group, 251; UIA group, 389). Significant associations were observed between race and ethnicity, SES, insurance type, and aneurysm rupture. Non-White race or ethnicity, lower SES, and having public or no insurance were associated with increased odds of aSAH presentation. The aSAH group had poorer functional outcomes and higher mortality rates than the UIA group. Patients who are non-White, have low SES, and have public or no insurance were disproportionately affected by aSAH, which is historically associated with poorer functional outcomes.
To investigate clinical differences in warm and cold complex regional pain syndrome (CRPS) phenotypes.
CRPS represents inhomogeneous chronic pain conditions; approximately 70% patients with CRPS have ..."warm" affected limbs and 30% have "cold" affected limbs.
We examined 50 patients with "cold" and "warm" CRPS (n = 25 in each group). Both groups were matched regarding age, sex, affected limb, duration of CRPS, and CRPS I and II to assure comparability. Detailed medical history and neurologic status were assessed. Moreover, quantitative sensory testing (QST) was performed on the affected ipsilateral and clinically unaffected contralateral limbs.
Compared with patients who had warm CRPS, patients who had cold CRPS more often reported a history of serious life events (p < 0.05) and chronic pain disorders (p < 0.05). In cold CRPS, the incidence of CRPS-related dystonia was increased (p < 0.05), and cold-induced pain had a higher prevalence (p < 0.01). Furthermore, QST revealed a predominant sensory loss in patients with cold CRPS (p < 0.05). In contrast, patients with warm CRPS were characterized by mechanical hyperalgesia (p < 0.05) in the QST of affected limbs.
Our results indicate that warm and cold complex regional pain syndromes (CRPS) are associated with different clinical findings, beyond skin temperature changes. This might have implications for the understanding of CRPS pathophysiology.
Pro-inflammatory cytokines–in particular tumor necrosis factor (TNF)-alpha–play an important role in pain and hyperalgesia. The stimuli inducing TNF-alpha release in humans and the time course of ...this release are largely unknown. We performed dermal microdialysis in healthy subjects (
n
=
36) during three experimental conditions: The first condition (control) was microdialysis without stimulation, the second condition was 30 min of electrical current stimulation (1 Hz, 20 mA, moderately painful), the third condition was 30 min of repetitive mechanical stimulation via an impact stimulator (bullet 0.5 g; velocity 11 m/s, minimally painful). TNF-alpha was quantified in the samples collected at the end of the baseline perfusion (about 1 h of saline perfusion), at the end of stimulation period (exactly 30 min after stimulation commenced) and at the end of the experiment (exactly 90 min after stimulation commenced) using a commercial enzyme-linked immunosorbent assay. The C-fiber-related flare was quantified with a laser-Doppler imager. ANOVA revealed that TNF-alpha levels increased during the eluate sampling period. At 90 min TNF-alpha in the eluate of the mechanical stimulation condition was significantly increased as compared to electrical current or control condition. Flare intensity was highest in the electrical current stimulation condition and only marginally different from control in mechanical stimulation. Our results show that minimal mechanical trauma is sufficient to induce significant TNF-alpha release in the skin. These results may be relevant to the treatment of posttraumatic pain disorders.
Minimized extracorporeal circulation (MECC, Maquet, Cardiopulmonary AG, Hirrlingen, Germany) is an established procedure to perform coronary revascularization. Studies showed positive effects of MECC ...compared to conventional cardiopulmonary bypass (CCPB) procedures in terms of transfusion requirements, less inflammation reactions, and neurological impairments. Recent retrospective studies showed higher mean arterial pressure (MAP) and a lower frequency of vasoactive drug use. We addressed this issue in this study. The hypothesis was to find a higher MAP during coronary bypass grafting surgery in patients treated with MECC systems. We performed a prospective, controlled, randomized trial with 40 patients either assigned to MECC (n = 18) or CCPB (n = 22) undergoing coronary bypass grafting. Primary endpoints were the perioperative course of mean arterial pressure, and the consumption of norepinephrine. Secondary endpoints were the regional cerebral and renal oxygen saturation (rSO2) as an indicator of area perfusion and the course of hematocrit. Clinical and demographic characteristics did not significantly differ between both groups. Thirty-day mortality was 0%. At four of five time points during extracorporeal circulation (ECC) MAP values were significantly higher in the MECC group compared to CCPB patients (after starting the ECC 60 +/- 11 mmHg vs. 49 +/- 10 mmHg, p = .002). MECC patients received significantly less norepinephrine (MECC 22.5 +/- 35 microg vs. CCPB 60.5 +/- 75 microg, p = .045). The rSO2 measured at right and left forehead and the renal area was similar for both groups during ECC and significantly higher at CCPB group 1 and 4 hours after termination of CPB. Minimized extracorporeal circulation provides a higher mean arterial pressure during ECC and we found a lower consumption of vasoactive drugs in the MECC group. There was a decrease in regional tissue saturation at 1 and 4 hours post bypass in the MECC group possibly due to increased systemic inflammation and extravascular fluid shift in the CCPB group.
Abstract Stress and thermoregulation both activate the sympathetic nervous system (SNS) but might differently affect pain. Studies investigating possible interactions in patients are problematic ...because of the high prevalence of SNS disturbances in patients. We therefore analyzed the influence of these different sympathetic challenges on experimentally-induced pain in healthy subjects. SNS was activated in two different ways: by mental stress (Stroop task, mental arithmetic task), and by thermoregulatory stimulation using a water-perfused thermal suit (7 °C, 32 °C, or 50 °C). Attentional effects of the mental stress tasks were controlled by using easy control tasks. Both, stress and thermoregulatory stimuli, robustly activated SNS parameters. However, the patterns of activation were different. While stress co-activated heart rate, blood pressure, peripheral vasoconstriction and sweating, thermal stimulation either increased blood pressure (cold) or heart rate and sweating (warm). Only stress was able to induce a significant reduction of pain. The control tasks neither activated the SNS nor altered pain perception. Our results suggest that (1) different patterns of sympathetic activation can be recorded after stress and thermoregulatory challenges and (2) that only stress is able to interfere with sensation of experimental pain. Whether SNS activation is causally responsible for analgesia needs to be further investigated.
Current interferometric gravitational wave detectors use the combination of quasi-monochromatic, continuous-wave laser light at 1064 nm and fused silica test masses at room temperature. Detectors of ...the third generation, such as the Einstein-Telescope, will involve a considerable sensitivity increase. The combination of 1550 nm laser radiation and crystalline silicon test masses at low temperatures might be important ingredients in order to achieve the sensitivity goal. Here we compare some properties of the fused silica and silicon test mass materials relevant for decreasing the thermal noise in future detectors as well as the recent technology achievements in the preparation of laser radiation at 1064 nm and 1550 nm relevant for decreasing the quantum noise. We conclude that silicon test masses and 1550 nm laser light have the potential to form the future building blocks of gravitational wave detection.
Complex regional pain syndromes (CRPS) are characterized by persistent and severe pain after trauma or surgery. Neuro-immune alterations are assumed to play a pathophysiological role. Here we set out ...to investigate whether patients with CRPS have altered systemic pro- and anti-inflammatory cytokine profiles compared to controls on mRNA and protein level. We studied blood cytokine mRNA and protein levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF), interleukin-2 (IL-2) and IL-8 and the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor-beta1 (TGF beta 1) in 40 prospectively recruited patients with CRPS I, two patients with CRPS II, and 34 controls. Quantitative real-time PCR and enzyme linked immunosorbent assay were used. Additionally, the patients underwent quantitative sensory testing and were assessed with the McGill pain questionnaire and the Hospital anxiety and depression scale. Patients with CRPS had higher blood TNF and IL-2 mRNA levels (p=0.005; p=0.04) and lower IL-8 mRNA levels (p<0.001) than controls. The mRNA for the anti-inflammatory cytokines IL-4 and IL-10 was reduced in the patient group (p=0.004; p=0.006), whereas TGF beta 1 mRNA levels did not differ between groups. These results were paralleled by serum protein levels, except for TGF beta 1, which was reduced in patients with CRPS, and for IL-8, which gave similar protein values in both groups. Sensory testing showed a predominant loss of small fiber-related modalities in the patient group. The shift towards a pro-inflammatory cytokine profile in patients with CRPS suggests a potential pathogenic role in the generation of pain.
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