Homajoun Maslehaty, Athanassios K. Petridis, Harald Barth and Hubertus Maximilian Mehdorn
The aim of this study was to evaluate the diagnostic value of MR imaging in perimesencephalic (PM) and nonperimesencephalic (non-PM) subarachnoid hemorrhage (SAH) of unknown origin.
The authors conducted a retrospective review of all patients with SAH (1226 patients) in their department between January 1991 and December 2008. Included in the study were cases of spontaneous SAH diagnosed using CT scans obtained within 24 hours of the initial symptoms and initially negative digital subtraction (DS) angiograms. Patients with traumatic SAH and an unknown history were excluded from the study. Patients with initially negative DS angiograms were divided into 2 groups: Group 1, a typically PM bleeding pattern (PM SAH); and Group 2, a non-PM bleeding pattern (non-PM SAH) such as hemorrhage in the sylvian or interhemispheric fissure. Cranial MR imaging including the craniocervical region was performed within 72 hours after SAH was diagnosed in all patients in Groups 1 and 2.
One thousand sixty-eight patients underwent DS angiography, and among them were 179 (16.7%) with negative angiograms—47 patients (26.3%) from Group 1 and 132 patients (73.7%) from Group 2. Magnetic resonance imaging demonstrated no bleeding sources in any case (100% negative). Thirty-four patients in Group 1 and 120 patients in Group 2 underwent a second DS angiography study. Digital subtraction angiography revealed an aneurysm as the bleeding source in 1 case in Group 1 and in 13 cases in Group 2.
Magnetic resonance imaging of the brain and craniocervical region did not produce additional benefit for the detection of a bleeding source and the therapy administered for PM SAH and non-PM SAH (100% negative). The costs of this examination exceeded the clinical value. Despite the results of this study, MR imaging should be discussed on a case-by-case basis because rare bleeding sources are periodically diagnosed in cases of non-PM SAH. A second-look DS angiogram is necessary because aneurysmal hemorrhage occasionally produces PM SAH as well as non-PM SAH. Further prospective studies are needed to verify the authors' results in the future.
Friederike Knerlich-Lukoschus, Beata von der Ropp-Brenner, Ralph Lucius, Hubertus Maximilian Mehdorn and Janka Held-Feindt
Central neuropathic pain is a frequent challenging complication after spinal cord injury (SCI), and specific therapeutic approaches remain elusive. The purpose of the present investigations was to identify potential key mediators of these pain syndromes by analyzing detailed expression profiles of important chemokines in an experimental SCI paradigm of posttraumatic neuropathic pain in rats.
Expression of CCR1, CCL3(MIP-1α), CXCR4, and CXCL12(SDF-1α) was investigated in parallel with behavioral testing for mechanical and thermal nociceptive thresholds after standardized SCI; 100-kdyn (moderate injury) and 200-kdyn (severe injury) force-defined thoracic spinal cord contusion lesions were applied via an Infinite Horizon Impactor at the T-9 level. Sham controls received laminectomies. Hindlimb locomotor function as well as mechanical and thermal sensitivities were monitored weekly by standardized behavioral testing after SCI. Chemokine expression was analyzed by real-time reverse transcriptase polymerase chain reaction in the early (7 days postoperatively) and late (42 days postoperatively) time courses after SCI, and immunohistochemical analysis (anatomical and quantitative) was performed 2, 7, 14, and 42 days after lesioning. Double staining with cellular markers and pain-related peptides (substance P and CGRP) or receptors (TRPV-1, TRPV-2, VRL-1, and TLR-4) was performed. Based on data obtained from behavioral testing, quantified immunohistochemical chemokine expressions in individual animals were correlated with the respective mechanical and thermal sensitivity thresholds 6 weeks after SCI.
After 200-kdyn lesions, the animals exhibited prolonged reduction in their nociceptive thresholds, while 100-kdyn groups showed pain-related behaviors only in the early time course after SCI. Investigated chemokines were widely induced after SCI, involving cervical, thoracic, and lumbar spinal cord levels far beyond the lesion core. CCR1 and CCL3 were induced significantly in the dorsal horns 2 days after lesioning and remained at high levels after SCI with significantly higher intensities after 200-kdyn than 100-kdyn contusions. CXCR4 and CXCL12 levels continuously increased from 2 to 42 days after moderate and severe lesions. Additionally, chemokines were induced significantly in dorsal columns, with highest density levels 42 days after 200-kdyn lesions. In dorsal horns, CCR1 was coexpressed with TRPV-1 while CXCR4 and CXCL12 were partially coexpressed with substance P and CGRP. In dorsal columns, CCL3/CCR1 colabeled with GFAP, TRPV-2, TRPV-1, TLR-4; CXCR4/CXCL12 coexpressed with GFAP, CD68/ED1, and TLR4. Chemokine immunoreactivity density levels, especially CCL3 and its receptor, correlated in part significantly with nociceptive thresholds.
The authors report lesion grade–dependent upregulation of different chemokines/chemokine receptors after spinal cord contusion lesions in pain-processing spinal cord regions in a clinically relevant model of traumatic SCI in rats. Prolonged chemokine induction further correlated with below-level pain development in the delayed time course after severe SCI and was coexpressed with pain-associated peptides and receptors, suggesting that chemokines play a crucial role in chronic central pain mechanisms after SCI.
Walter Stummer, Jörg-Christian Tonn, Hubertus Maximilian Mehdorn, Ulf Nestler, Kea Franz, Claudia Goetz, Andrea Bink and Uwe Pichlmeier
Accumulating data suggest more aggressive surgery in patients with malignant glioma to improve outcome. However, extended surgery may increase morbidity. The randomized Phase III 5-aminolevulinic acid (ALA) study investigated 5-ALA–induced fluorescence as a tool for improving resections. An interim analysis demonstrated more frequent complete resections with longer progression-free survival (PFS). However, marginal differences were found regarding neurological deterioration and the frequency of additional therapies. Presently, the authors focus on the latter aspects in the final study population, and attempt to determine how safety might be affected by cytoreductive surgery.
Patients with malignant gliomas were randomized for fluorescence-guided (ALA group) or conventional white light (WL) (WL group) microsurgery. The final intent-to-treat population consisted of 176 patients in the ALA and 173 in the WL group. Primary efficacy variables were contrast-enhancing tumor on early MR imaging and 6-month PFS. Among secondary outcome measures, the National Institutes of Health Stroke Scale (NIH-SS) score and the Karnofsky Performance Scale (KPS) score were used for assessing neurological function.
More frequent complete resections and improved PFS were confirmed, with higher median residual tumor volumes in the WL group (0.5 vs 0 cm3, p = 0.001). Patients in the ALA group had more frequent deterioration on the NIH-SS at 48 hours. Patients at risk were those with deficits unresponsive to steroids. No differences were found in the KPS score. Regarding outcome, a combined end point of risks and neurological deficits was attempted, which demonstrated results in patients in the ALA group to be superior to those in participants in the WL group. Interestingly, the cumulative incidence of repeat surgery was significantly reduced in ALA patients. When stratified by completeness of resection, patients with incomplete resections were quicker to deteriorate neurologically (p = 0.0036).
Extended resections performed using a tool such as 5-ALA–derived tumor fluorescence, carries the risk of temporary impairment of neurological function. However, risks are higher in patients with deficits unresponsive to steroids.