A case of hippocampal laminar necrosis following complex partial status epilepticus

Cortical laminar necrosis (CLN) is a metabolic injury pattern usually observed after cerebral hypoxia, hypoglycemia, or ischemia. We report serial magnetic resonance imaging findings in a patient with complex partial status epilepticus (SE) developing a band-like, T1-hyperintense lesion consistent with CLN along the surface of the left hippocampus without concurrent other causes of CLN. This observation suggests a direct pathogenetic link between SE and CLN involving combined damage to neurons and glia.     

Visualization of degenerating axons in a dysmyelinating mouse mutant with axonal loss

Mice homozygously deficient for the myelin component P0 show loss of axons in peripheral nerves. In order to investigate the morphological characteristics of degenerating axons, we crossbred the myelin mutants with a transgenic mouse line expressing yellow fluorescent protein (YFP) in a small proportion of neurons. Peripheral nerves of the double mutants were prepared into small fiber bundles and investigated by fluorescence microscopy. We could identify the tips of degenerating axon as bulb-like structures. Additionally, by electron microscopy, these structures were characterized as axoplasmic extensions containing numerous membraneous compartments. By immunoelectron microscopy, the degenerating end bulbs were in contact with ensheathing Schwann cells that contained YFP-immunoreactivity possibly reflecting phagocytosis of axon material by these cells. Immunohistochemistry using antibodies against macrophages revealed that YFP-positive bulbs, but also other axonal swellings, were often associated with macrophages supporting our previous findings that myelin-related axonal loss is partially mediated by these cells.     

Marlin-1 and conventional kinesin link GABAB receptors to the cytoskeleton and regulate receptor transport

The cytoskeleton and cytoskeletal motors play a fundamental role in neurotransmitter receptor trafficking, but proteins that link GABA(B) receptors (GABA(B)Rs) to the cytoskeleton have not been described. We recently identified Marlin-1, a protein that interacts with GABA(B)R1. Here, we explore the association of GABA(B)Rs and Marlin-1 to the cytoskeleton using a combination of biochemistry, microscopy and live cell imaging. Our results indicate that Marlin-1 is associated to microtubules and the molecular motor kinesin-I. We demonstrate that a fraction of Marlin-1 is mobile in dendrites of cultured hippocampal neurons and that mobility is microtubule-dependent. We also show that GABA(B)Rs interact robustly with kinesin-I and that intracellular membranes containing GABA(B)Rs are sensitive to treatments that disrupt a protein complex containing Marlin-1, kinesin-I and tubulin. Finally, we report that a kinesin-I mutant severely impairs receptor transport. We conclude that Marlin-1 and kinesin-1 link GABA(B)Rs to the tubulin cytoskeleton in neurons.     

Reversibility and time-dependency of contrast medium induced inhibition of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) conversion in renal proximal tubular cells in vitro: comparison of a monomeric and a dimeric nonionic iodinated contrast medium

OBJECTIVES: To evaluate the time-course and reversibility of toxicity of a low-osmolar and an iso-osmolar radiographic contrast medium on renal tubular cell cultures. MATERIALS AND METHODS: LLC-PK1-cells were incubated with iomeprol, iodixanol, and mannitol (4.7-75 mg I/mL, 2-24 hours). Metabolic activity was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-(MTT) assay. RESULTS: Iomeprol and iodixanol induced a time- and dose-dependent inhibition of MTT conversion (75%-19% and 70%-23% of control for iomeprol and iodixanol, respectively, at concentrations ranging from 4.7 to 75 mg I/mL after an incubation time of 2 hours and 64%-14% and 65%-12% of control after 24 hours). The mannitol induced inhibition of the MTT conversion was significantly weaker than that induced by iomeprol (99%-47% of control at concentrations corresponding to 4.7-75 mg I/mL after an incubation time of 24 hours, P < 0.001). After 24 hours incubation with iomeprol, iodixanol, or mannitol and a recovery time of 2 hours after removal of the test-solutions, there was only a small inhibition of MTT-conversion (89%, 88%, and 95% of control at 75 mg I/mL). CONCLUSIONS: Contrast medium induced cytotoxicity consisted of a reversible part and an irreversible part. There was no difference in cytotoxicity between iomeprol and iodixanol over a broad range of concentrations and incubation-times.     

Influence of attenuation correction by integrated low-dose CT on somatostatin receptor SPECT

AIM: Somatostatin receptor scintigraphy (SRS) is well-established in neuroendocrine tumour (NET) imaging. This study evaluated the impact of attenuation correction (AC) on SRS SPECT data in patients examined by SPECT-CT. METHODS: Planar scintigraphy and SPECT-CT of 17 patients (10 men, seven women; age, 40-74 years; mean, 62 years) suffering from NET were included. For the visual assessment of AC, the intensity and contrast of foci classified as pathological were rated in both the non-attenuation corrected (NAC) and the attenuation corrected (AC) SPECT images using a 5-point score. The change in signal intensity after AC was semiquantified two-fold for each focus in both SPECT(AC) and SPECT(NAC): firstly by using tumour-to-background (TB) ratios (defined as T(max)/B(mean)) for the determination of a TB(AC)/TB(NAC) ratio. Secondly, by a T(max,AC)/T(max,NAC) ratio. Both ratios were correlated to the focus depth. RESULTS: A total of 46 pathological foci were found. Focus contrast and intensity significantly increased in 14/46 foci (30%) after AC (mean, 3.7-4.0) in the visual analysis (P<0.001). While TB ratios increased only in 24/46 foci after AC and no correlation between the T(BAC)/T(BNAC) ratio and focus depth (r=0.027; P=0.856) was found, T(max) was higher after AC in all foci and the T(max,AC)/T(max,NAC) ratio showed the expected correlation to focus depth (r=0.650; P<0.01), indicating the superiority of the Tmax approach for the demonstration of the effects of attenuation correction on focal uptake. CONCLUSION: Attenuation correction of SRS SPECT data by SPECT-CT results in visually more clearly contrasted foci. Moreover, as focus intensity increases, especially in the more centrally localised foci, CT-based AC has a potential to further improve the sensitivity of SRS SPECT.     

Assessment of local control after laser-induced thermotherapy of liver metastases from colorectal cancer: contribution of FDG-PET in patients with clinical suspicion of progressive disease

BACKGROUND: Management of patients after locally ablative treatment of liver metastases requires exact information about local control and systemic disease status. To fulfill these requirements, whole-body imaging using positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) is a promising alternative to morphologic imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). PURPOSE: To evaluate FDG-PET for the assessment of local control and systemic disease in patients with clinical suspicion of tumor progression after laser-induced thermotherapy (LITT) of colorectal liver metastases. MATERIAL AND METHODS: In 21 patients with suspicion of progressive disease after LITT, whole-body FDG-PET was performed. The presence of viable tumor within treated lesions, new liver metastases, and extrahepatic disease was evaluated visually and semiquantitatively (maximal standard uptake value [SUV(max)], tumor-to-normal ratio [T/N]). The standard of reference was histopathology (n = 25 lesions) and/or clinical follow-up (>12 months) including contrast-enhanced MRI of the liver. RESULTS: Among 54 metastases treated with LITT, 29 had residual tumor. Receiver operating characteristic (ROC) analysis of SUV(max) (area under the curve (AUC) 0.990) and T/N (AUC 0.968) showed a significant discrimination level of negative or positive lesion status with an equal accuracy of 94% (51/54). The overall accuracy of visual FDG-PET was 96% (52/54), with one false-negative lesion among six examined within 3 days after LITT, and one false-positive lesion examined 54 days after LITT. In the detection of new intra- and extrahepatic lesions, FDG-PET resulted in correct alteration of treatment strategy in 43% of patients (P = 0.007). CONCLUSION: FDG-PET is a promising tool for the assessment of local control and whole-body restaging in patients with clinical suspicion of tumor progression after locally ablative treatment of colorectal liver metastases with LITT.     

Effects of short-term treatment strategies over 4 weeks in Achilles tendinopathy

Background

The therapeutic efficacy of non‐surgical treatment strategies in Achilles tendinopathy (AT) has not been well clarified. Time‐consuming and costly combinations of treatment for pain, physiotherapy and biomechanical procedures are often applied.

Objective

To analyse the efficacy of single therapeutic regimens commonly used over a short period of 4 weeks.

Methods

31 male runners (mileage >32 km/week) with unilateral, untreated AT completed 4 weeks of either physiotherapy (10 treatments: deep‐friction, pulsed ultrasound, ice, sensory motor training; (P)), wearing custom fit semirigid insoles (I) or remained without treatment (control group C). Before and after treatment, all patients underwent a treadmill test and a plantar flexion strength exercise. Subjective pain (Pain Disability Index, Pain Experience Scale), as well as strength performance capacity (peak torque), was analysed (mean, 95% CI, repeated measures analysis of variance, α = 0.05).

Results

Pain was reduced to <50% of the baseline value after physiotherapy or after wearing insoles (p<0.05). Individual pain reduction was >50% (25%) in 89% (100%) of subjects in I and 55% (73%) in P. Higher eccentric plantar flexion peak torques after treatment were observed in I and P.

Conclusions

Most patients with AT experience a reduction in pain after only 4 weeks of differentiated, non‐surgical treatment consisting of physiotherapy or semirigid insoles.Problems of Achilles tendon overuse are cited as one of the major pathologies that reduce physical capacity in everyday living, occupation and sports.^1,2,3 Owing to the long duration of problems and widely varying, individual responses to treatment, the efficacy of single or combined therapeutic measures still remains a matter of debate.^4,5 Thus, treatment is usually complex, time consuming and costly.^3,5It has often been assumed that Achilles tendon problems are caused by an inflammation.⁶ However, recent histological studies show that inflammatory cells and mediators, usually present after acute mechanical stress, are absent in tendon overuse.^7,8,9 On the other hand, high concentrations of glycosaminoglycans and a loss of the hierarchical collagen structure have been found.^10,11The mechanism of pain development is not well understood. Competing explanatory models describe increased mechanical tendon vulnerability, microruptures and the supplanting of collagen type I by type III. Pain is also ascribed to the mechanical irritation of ingrown nerve endings due to neovascularisation.^1,9 Reduced perfusion is now considered less important since it was demonstrated that blood supply and oxygen extraction clearly increase during physical exercise.^12,13 It thus seems certain that tendon tissue must be considered metabolically active to a far greater extent than has been assumed to date.^8,9Pain reduction has traditionally been the main outcome variable of non‐surgical treatment in Achilles tendinopathy (AT).³ In daily practice, local physiotherapeutic measures such as deep friction massages, ice and ultrasound are usually applied.^14,15,16 However, despite broad acceptance and pain reduction in individual cases, scientific evidence of short‐term physiotherapy is still lacking.¹⁴ Currently, adjuvant use of sensory motor training¹⁸ and eccentric exercises^18,19,20 are increasingly being discussed. Shalabi et al²¹ demonstrated that eccentric exercises led to an improved clinical outcome, reduction in tendon diameter and reduced intratendinous lesions. Alfredson et al^18,19 had comparably good clinical results after 12 weeks of predominantly eccentric exercise training.In addition to physiotherapy and training, custom‐made insoles are frequently used, but evidence of their efficacy is still lacking.^15,16 Recent studies using bone pins have shown that the mechanical effect of insoles, understood as an alignment of the skeleton, is unspecific and only slight during walking and running.²² Currently, sensory motor effects of semirigid insoles are being discussed.^23,24The aim of this study was to analyse whether standardised short‐term physiotherapy or wearing individually fitted insoles over a period of 4 weeks reduces pain in patients with unilateral AT.     

Evaluation of optimal echo time for 1H-spectroscopic imaging of brain tumors at 3 Tesla

PURPOSE: To compare the spectral quality of short echo time (TE) MR spectroscopic imaging (MRSI, TE = 30 msec) with long-TE MRSI (TE = 144 msec) at 3 Tesla in normal brain and tumor tissue. MATERIALS AND METHODS: Spectroscopic imaging (chemical-shift imaging (CSI)) data of 32 patients with histopathological confirmed brain lesions were acquired at 3 Tesla (3T) using TEs of 30 msec and 144 msec. Tumor-relevant metabolites (trimethylamine (TMA), creatine compounds (tCr), and N-acetylated compounds (tNAA)) were analyzed with LCModel software, which applies prior knowledge by performing a frequency domain fit using a linear combination of model spectra. RESULTS: Short-TE spectra provided up to twice the signal-to-noise ratio (SNR) compared to TE = 144 msec. The estimated fitting error was improved up to 30% for TMA and tCr, but was slightly reduced (10%) for tNAA. Quantification in terms of absolute concentrations was consistent at both TEs. CONCLUSION: Since other metabolites observable at TE < 30 msec may be of diagnostic relevance, short-TE MRSI should be the preferred method at 3T for the evaluation of focal lesions in brain tissue; however, TE = 144 msec can serve as an option for MRS in regions with potential baseline problems.     

Assessment of intra- and interobserver reproducibility of rest and cold pressor test-stimulated myocardial blood flow with <Superscript>13</Superscript>N-ammonia and PET

Purpose We investigated the intraobserver reproducibility of myocardial blood flow (MBF) measurements with PET at rest and during cold pressor test (CPT), and the interobserver agreement. Methods Twenty normal volunteers were studied. Using ¹³N-ammonia, MBF was measured at rest and during CPT and measurement was repeated in a 1-day session (short-term reproducibility; SR). After a follow-up of 2 weeks, MBF was measured again at rest and during CPT and compared with the initial baseline measurement (long-term reproducibility; LR). In addition, adenosine-induced hyperemic MBF increases were assessed. Results Assessment of the SR did not show a significant absolute difference in MBF at rest, MBF during CPT or the endothelium-related change in MBF from rest to CPT (ΔMBF) (0.09 ± 0.10, 0.11 ± 0.09, and 0.08 ± 0.05 ml/g/min; p = NS), and they were linearly correlated (r = 0.72, r = 0.76 and r = 0.84; p < 0.0001). Corresponding values for standard error of the estimate (SEE), as indicative for the range of MBF measurement error, were 0.14, 0.14, and 0.09 ml/g/min. The LR yielded relatively higher but non-significant absolute differences in the MBF at rest, MBF during CPT and ΔMBF (0.10 ± 0.10, 0.14 ± 0.10, and 0.19 ± 0.10 ml/g/min; p = NS), and paired MBFs significantly correlated (r = 0.75, r = 0.71, and r = 0.60; p < 0.001). Corresponding SEEs were 0.13, 0.15, and 0.16 ml/g/min. The interobserver analysis yielded a high correlation for MBF at rest, MBF during CPT, and hyperemic MBF (r = 0.96, SEE=0.04; r = 0.78, SEE=0.11; and r = 0.87, SEE=0.28; p < 0.0001, respectively), and also a good interobserver correlation for ΔMBF (r = 0.62, SEE=0.09; p < 0.003). Conclusion Short- and long-term MBF responses to CPT, as an index for endothelium-related coronary vasomotion, can be measured reproducibly with ¹³N-ammonia PET. In addition, the high interobserver reproducibility for repeat analysis of MBF values suggests the measurements to be largely operator independent. Thomas H. Schindler and Xiao-Li Zhang contributed equally to this paper.     

Analgetikakombinationen zur postoperativen Schmerztherapie

BACKGROUND: The supplementation of an opioid by a non-opioid analgesic is a widely accepted technique for the treatment of postoperative pain. However, it is still unclear whether a combination of different non-opioids has an advantage in terms of an improved analgesia and/or a reduction of the opioid-related adverse effects. METHODOLOGY: A systematic analysis of the literature was performed searching for randomized, controlled trials studying the effects of a combination of two non-opioid analgesics in order to reduce postoperative opioid requirements and/or postoperative pain. Significant reduction of the postoperative opioid requirement and/or postoperative pain were defined as main rating criteria. To facilitate comparisons between the trials, the relative (proportional) reduction of postoperative opioid administration and the relative reduction of postoperative pain were calculated on defined pain scales. RESULTS: A total of 25 trials were identified, mainly studies comparing non-steroidal anti-inflammatory drugs (NSAIDs) with paracetamol. Only 3 trials found a statistically improved analgesic efficacy and 15 studies did not show any relevant improvement or the combination group was only significantly superior to one of the groups receiving monotherapy. A further seven studies could not be evaluated due to methodological issues. There was no evidence for a significant reduction of opioid-induced adverse effects. CONCLUSION: A combination of non-opioid analgesics, in particular NSAIDs with paracetamol, cannot be recommended at present due to the lack of data showing improved effectiveness.