Different Glymphatic Kinetics in Spontaneous Intracranial Hypotension.

BACKGROUND AND PURPOSE: The glymphatic (glia-lymphatic) system is a paravascular pathway for the clearance of waste metabolites including amyloid ß from the brain. Serial T1 relaxation time measurements after the intrathecal injection of gadolinium-based contrast agents facilitate the analysis of the temporal dynamics that may be different in patients with spontaneous intracranial hypotension (SIH) and those without SIH. MATERIALS AND METHODS: 3D T1-weighted magnetization-prepared 2 rapid gradient echo sequences were acquired in 4 patients with SIH with proved CSF leaks and 12 patients without SIH before, 2-4, 6-8, and 24-48 hours after intrathecal gadobutrol injection. MR scans were warped to the Montreal Neurological Institute space and serial scans were coregistered. T1 relaxation times were measured in predefined ROIs including the subarachnoid space, cortex, white matter, and cervical lymph nodes. RESULTS: In the subarachnoid space and cortex, T1 relaxation times decreased after 2-4 and 6-8 hours before they increased again. In contrast, in the white matter of the temporal lobe T1 relaxation time still decreased after 24-48 hours. There was a striking difference in patients with SIH who did not show a clear contrast distribution within the brain parenchyma. CONCLUSIONS: T1 relaxation time curves are compatible with a convective flow driven by arterial pulsations via paravascular spaces surrounding penetrating arteries into the brain's interstitial fluid in the deep white matter. Different curves in patients with SIH and those without SIH indicate that the CSF pressure also impacts the temporal kinetics of the glymphatic system.

Spinal dementia: Don't miss it, it's treatable.

BACKGROUND & PURPOSE: Around 5% of dementia patients have a treatable cause. To estimate the prevalence of two rare diseases, in which the treatable cause is at the spinal level. METHODS: A radiology information system was searched using the terms CT myelography and the operation and classification system (OPS) code 3-241. The clinical charts of these patients were reviewed to identify patients with a significant cognitive decline. RESULTS: Among 205 patients with spontaneous intracranial hypotension (SIH) and proven CSF leaks we identified five patients with a so-called frontotemporal brain sagging syndrome: Four of those had CSF venous fistulas and significantly improved by occluding them either by surgery or transvenous embolization. Another 11 patients had infratentorial hemosiderosis and hearing problems and ataxia as guiding symptoms. Some cognitive decline was present in at least two of them. Ten patients had ventral dural tears in the thoracic spine and one patient a lateral dural tear at C2/3 respectively. Eight patients showed some improvement after surgery. DISCUSSION: It is mandatory to study the (thoracic) spine in cognitively impaired patients with brain sagging and/ or infratentorial hemosiderosis on MRI. We propose the term spinal dementia to draw attention to this region, which in turn is evaluated with dynamic digital subtraction and CT myelography.

Effect of tibial plateau angle < 5° on ground reaction forces in dogs treated with tibial plateau leveling osteotomy for cranial cruciate ligament rupture up to 6 months postoperatively.

Tibial plateau leveling osteotomy (TPLO) has been commonly performed in dogs with cranial cruciate ligament disease (CCLD) since the introduction by Slocum and Slocum (1993). To reduce cranial tibial thrust the TPLO technique aims for a postoperative tibial plateau angle (TPA) of 5-6.5°. In recent years studies have shown that a postoperative TPA below 5° could be beneficial regarding stifle stability or meniscal load. Dogs with CCLD that were treated with TPLO, were examined preoperatively, six weeks, three and six months postoperatively with gait analysis and grouped according to their postoperative TPA. The aims of study was (1) to evaluate if dogs with a postoperative TPA below 5° would have a faster limb function recovery up to six months postoperatively as measured objectively with ground reaction forces (GRFs) and (2) to determine whether the postoperative TPA correlates with the outcome measurements. Dogs with TPA <5° showed no faster limb function recovery postoperatively up to six months as measured with peak vertical force (PVF) or vertical impulse (VI) (p > 0.05). No correlation for the postoperative TPA <5° on GRFs was demonstrated. But the postoperative TPA showed a significant correlation with the symmetry indices of PVF (SIPVF) and VI (SIVI) for all dogs (>5° and <5° TPA together), indicating that with lower postoperative TPA dogs had a more symmetrical gait in hindlimbs SIPVF (r = 0.144, p < 0.05) and SIVI (r = 0.189, p < 0.01). The study indicates that a lower postoperative TPA could be beneficial regarding hindlimb symmetry indices of GRFs.

Effect of intra-articular platelet-rich plasma or hyaluronic acid on limb function recovery in dogs with TPLO for cranial cruciate ligament rupture: a randomised controlled trial.

OBJECTIVES: This study aimed to investigate the recovery of limb function following a single intra-articular injection of platelet-rich plasma or hyaluronic acid in dogs with cranial cruciate ligament rupture treated with tibial plateau levelling osteotomy compared to dogs receiving no injection intraoperatively. MATERIALS AND METHODS: Sixty-two dogs with cranial cruciate ligament rupture, body weights of 20 to 40 kg, and no other orthopaedic conditions were enrolled in this prospective, randomised, double-blind, controlled study at the small animal clinic at LMU Munich. All dogs underwent tibial plateau levelling osteotomy. Based on random allocation, they received either a single intra-articular injection of platelet-rich plasma, hyaluronic acid or no injection intraoperatively. Gait analysis, clinical examinations, radiography of the stifle joint for osteoarthritis progression and two validated owner questionnaires were compared among groups at three timepoints postoperatively (6 weeks, 3 and 6 months). Limb function was primarily assessed by measuring the ground reaction forces. RESULTS: At all times postoperatively, no differences were observed among groups regarding clinical examinations, osteoarthritis score values, ground reaction forces or owner questionnaires. All dogs showed significant improvement in limb function clinically, in all ground reaction forces and in the validated questionnaires. Osteoarthritis progressed minimally during rechecks in all dogs regardless of the additional injection or not. CLINICAL SIGNIFICANCE: All dogs treated with tibial plateau levelling osteotomy for cranial cruciate ligament rupture showed improvements in limb function. No additive effect on faster recovery was demonstrated with the additional intra-articular injection of platelet-rich plasma or hyaluronic acid. Addition of platelet-rich plasma/hyaluronic acid injections during tibial plateau levelling osteotomy is unnecessary considering the lack of benefit observed up to 6 months postoperatively.

Conebeam CT as an Additional Tool in Digital Subtraction Myelography for the Detection of Spinal Lateral Dural Tears.

Lateral dural tears as a cause spontaneous intracranial hypotension occur in ∼20% of patients. Common imaging modalities for their detection are lateral decubitus digital subtraction myelography or dynamic CT myelography. Reports on the use of conebeam CT are scarce. We show 3 patients in whom the targeted use of conebeam CT during digital subtraction myelography was helpful in confirming the site of the leak.

[IQWiG's methods for the cost-benefit assessment : Comparison with an international reference scenario]. / Wo steht die Kosten-Nutzen-Bewertung des IQWiG : Abgleich mit einem internationalen Referenzszenario?

Standardization of international health economic guidelines has been repeatedly requested. In this context, an international reference case was proposed, which constitutes an agreed approach for the key elements of health economic evaluation including study perspective, comparators, source of effectiveness data, role of modeling, main (economic) outcome, source of utilities, characterizing uncertainty. It is, however, questionable whether such a reference scenario can reasonably be applied across all health care systems. Our analysis pursues the question to which degree the Institute for Quality and Efficiency in Health Care's (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG) "General methods for evaluating the relation between cost and benefit" comply with the key elements of the reference case. In case of divergences, they will be described and discussed in light of the German social legislation and in consideration of current scientific evidence. In conclusion, the analysis revealed that IQWiG complied with the reference case in almost all aspects. Differences were found only with respect to the choice of main (economic) outcome and the source of utilities. These differences seem justified and well explained in the context of the German social legislation as well as in view of the weaknesses of the quality-adjusted life year (QALY) concept.

Benzofuran based PDE4 inhibitors.

Replacement of the 3,4-dialkoxyphenyl substructure common to a number of PDE4 inhibitors with a 2-alkyl-7-methoxybenzofuran unit is described. This substitution can result in either enhancement or substantial reductions in PDE4 inhibitory activity depending on the system to which it is applied. An in vitro SAR study of a potent series of 4-(2-heteroaryl-ethyl)-benzoiurans 26 is also presented.

Anionic- and lipophilic-mediated surface binding inhibitors of human leukocyte elastase.

We report the synthesis of a series of diphenylmethane-based oligomers containing anionic and lipophilic functionalities that are potent inhibitors of human leukocyte elastase (HLE). The enzyme inhibition is regulated by the size of the oligomer, as well as, the number of charges. Lipophilicity is an important element in determining potency and specificity against other basic enzymes. Compounds whose scaffolds contain three phenoxyacetic acid groups and three alkyl ethers are competitive and specific inhibitors of HLE with Ki = 20 nM. The mechanism of action of this class of compounds is believed to involve multidendate interactions with the surface of HLE near the active site which prevents substrate access to the catalytic site.

Scattering functions near the Sun by large aerosols.

In the course of a lengthy series of observations since 1975, a large, continuous decrease of the brightness of the solar aureole has been found west of Boston, at Hanscom Air Force Base and at Lexington, Mass. This points to the virtual disappearance from the lower atmosphere of giant particles larger than ~ 10 microm. in size while total suspended particulates in Boston and other U.S. cities have barely decreased. Results of calculations to better understand the relation between forward scattering and aerosol mass distribution [coarse fraction (CF)] are presented. In addition, a method to modify steep scattering functions calculated for a plane-wave source (Sun treated as a star) to those of the actual (and limb-darkened) Sun is presented. The calculated wavelength dependence of extinction, which is lower than that observed, is found to be little affected by the CF, but seems, like forward scattering, to be sensitive to mass distribution of sizes of < 0.4 and ~ 0.6 microm because of the anomal scattering behavior of spheres.

Simple method for checking the beam path in reflective Fourier-transform infrared optics.

A simple method is described that yields, in reflective optics as well as in Fourier-transformin frared spectrometers,a beam of bright visible light coincident with the invisible infrared beam so that foci and beam locations can be checked easily.

Measurements of the skylight scattering function.

A small, handheld skylight photometer, incorporated into a sun photometer and capable of measuring sky radiation to within 2 degrees of the sun at lambda 0.50 and 0.93 microm is described. Calibration procedures are discussed; solar measurements in the wideband 0.93-microm channel show the expected influence of water vapor. Formulas to obtain the aerosol scattering function are presented. Samples of measured and theoretical aerosol scattering functions are discussed.

Infrared optical constants of aerosols at some locations.

Spectra of absorption indices and data on gross chemical composition for two size classes of water soluble and dust fractions of high-volume aerosol samples are presented for several locations (mainly Bedford, Massachusetts; Meppen in Germany; Riverside and San Nicolas Island in California and some maritime locations). The absorption data were obtained by the KBr-pressed disk method. It has been found that re-grinding of the pellets increases the absorption by salt samples considerably.

Zenith polarization and color ratio during twilight.

The excellent data of zenith polarization and color ratio (CR) during twilight obtained by Coulson at the Mauna Loa Observatory, Hawaii are subjected to a reinterpretation, especially with regard to the frequent deviations from the clear average. It is shown that a moderate lift of the earth's shadow by distant clouds (or by low level haze) will reduce the red/green CR, while greater lift shifts the CR peak to a smaller solar depression. The effect on zenith polarization at wavelengths >/=0.6 microm is seen to correspond to a slight reduction of overall polarization for a moderate lift, and for a large lift to a shift of the polarization minimum (depolarization by stratospheric aerosol) from 4 degrees solar depression angle to 2 degrees . A generally high level of polarization, but with a barely noticeable 4 degrees minimum, had also been observed earlier in Germany by Steinhorst when the stratospheric aerosol load was very small. The difference is explained by a higher and stronger aerosol layer in the tropics combined with a higher and cleaner troposphere.

Volcanic twilights from the fuego eruption.

Striated twilight glows have been observed since 26 November 1974 in New England, indicating the spread of stratospheric dust earlier observed over Arizona. Similar photometric results were obtained from New Mexico and Florida, and twilights in Puerto Rico showed features not hitherto measured. Letters and verbal reports indicate the source to be eruptions of Fuego Volcano in Guatemala between 13 and 23 October 1974.