Reversible cerebral vasoconstriction syndrome with concurrent bilateral carotid artery dissection.

BACKGROUND: The pathophysiological basis of reversible cerebral vasoconstriction syndrome is poorly understood but carotid artery dissection has been discussed as a rare possible cause. So far, only single cases of unilateral carotid artery dissection and reversible cerebral vasoconstriction syndrome have been reported. CASE: Here, we describe the case of a 54-year old patient presenting to the emergency department with right hemiparesis, hypaesthesia and dysarthria. Furthermore, he reported two episodes of thunderclap headache after autosexual activity. Cerebral imaging showed ischaemic infarcts, slight cortical subarachnoid haemorrhage, bilateral carotid artery dissection and fluctuating intracranial vessel irregularities, compatible with reversible cerebral vasoconstriction syndrome. An extensive diagnostic work-up was normal. No typical trigger factors of reversible cerebral vasoconstriction syndrome could be found. The patient received intravenous heparin and the calcium channel blocker nimodipine. Follow-up imaging revealed no vessel irregularities, the left internal carotid artery was still occluded. CONCLUSION: This case supports the assumption that carotid artery dissection should be considered as a potential trigger of reversible cerebral vasoconstriction syndrome, possibly by altering sympathetic vascular tone.

Biomechanical comparison of menisci from different species and artificial constructs.

BACKGROUND: Loss of meniscal tissue is correlated with early osteoarthritis but few data exist regarding detailed biomechanical properties (e.g. viscoelastic behavior) of menisci in different species commonly used as animal models. The purpose of the current study was to biomechanically characterize bovine, ovine, and porcine menisci (each n = 6, midpart of the medial meniscus) and compare their properties to that of normal and degenerated human menisci (n = 6) and two commercially available artificial scaffolds (each n = 3). METHODS: Samples were tested in a cyclic, minimally constraint compression-relaxation test with a universal testing machine allowing the characterization of the viscoelastic properties including stiffness, residual force and relative sample compression. T-tests were used to compare the biomechanical parameters of all samples. Significance level was set at p < 0.05. RESULTS: Throughout cyclic testing stiffness, residual force and relative sample compression increased significantly (p < 0.05) in all tested meniscus samples. From the tested animal meniscus samples the ovine menisci showed the highest biomechanical similarity to human menisci in terms of stiffness (human: 8.54 N/mm ± 1.87, cycle 1; ovine: 11.24 N/mm ± 2.36, cycle 1, p = 0.0528), residual force (human: 2.99 N ± 0.63, cycle 1 vs. ovine 3.24 N ± 0.13, cycle 1, p = 0.364) and relative sample compression (human 19.92% ± 0.63, cycle 1 vs. 18.72% ± 1.84 in ovine samples at cycle 1, p = 0.162). The artificial constructs -as hypothesized- revealed statistically significant inferior biomechanical properties. CONCLUSIONS: For future research the use of ovine meniscus would be desirable showing the highest biomechanical similarities to human meniscus tissue. The significantly different biomechanical properties of the artificial scaffolds highlight the necessity of cellular ingrowth and formation of extracellular matrix to gain viscoelastic properties. As a consequence, a period of unloading (at least partial weight bearing) is necessary, until the remodeling process in the scaffold is sufficient to withstand forces during weight bearing.

Calretinin as a Marker for Premotor Neurons Involved in Upgaze in Human Brainstem.

Eye movements are generated by different premotor pathways. Damage to them can cause specific deficits of eye movements, such as saccades. For correlative clinico-anatomical post-mortem studies of cases with eye movement disorders it is essential to identify the functional cell groups of the oculomotor system in the human brain by marker proteins. Based on monkey studies, the premotor neurons of the saccadic system can be identified by the histochemical markers parvalbumin (PAV) and perineuronal nets in humans. These areas involve the interstitial nucleus of Cajal (INC) and the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), which both contain premotor neurons for upgaze and downgaze. Recent monkey and human studies revealed a selective excitatory calretinin (CR)-positive input to the motoneurons mediating upgaze, but not to those for downgaze. Three premotor regions were identified as sources of CR input in monkey: y-group, INC and RIMLF. These findings suggest that the expression pattern of parvalbumin and CR may help to identify premotor neurons involved in up- or downgaze. In a post-mortem study of five human cases without neurological diseases we investigated the y-group, INC and RIMLF for the presence of parvalbumin and CR positive neurons including their co-expression. Adjacent thin paraffin sections were stained for the aggrecan (ACAN) component of perineuronal nets, parvalbumin or CR and glutamate decarboxylase. The comparative analysis of scanned thin sections of INC and RIMLF revealed medium-sized parvalbumin positive neurons with and without CR coexpression, which were intermingled. The parvalbumin/CR positive neurons in both nuclei are considered as excitatory premotor upgaze neurons. Accordingly, the parvalbumin-positive neurons lacking CR are considered as premotor downgaze neurons in RIMLF, but may in addition include inhibitory premotor upgaze neurons in the INC as indicated by co-expression of glutamate decarboxylase in a subpopulation. CR-positive neurons ensheathed by perineuronal nets in the human y-group are considered as the homolog premotor neurons described in monkey, projecting to superior rectus (SR) and inferior oblique (IO) motoneurons. In conclusion, combined immunostaining for parvalbumin, perineuronal nets and CR may well be suited for the specific identification and subsequent analysis of premotor upgaze pathways in clinical cases of isolated up- or downgaze deficits.

Targeted high-throughput sequencing identifies a TARDBP mutation as a cause of early-onset FTD without motor neuron disease.

Targeted high-throughput sequencing of many amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) genes in parallel has the potential to reveal novel ALS- and/or FTD-phenotypes and to provide missing links on the ALS-FTD continuum. For example, although the 43-kDa transactive response DNA binding protein is the major pathologic hallmark linking ALS and FTD, mutations in the gene encoding 43-kDa transactive response DNA binding protein (TARDBP) have been appreciated only as a cause of ALS-phenotypes, but not yet of pure FTD. Thus, the genetic link is not yet well substantiated that TARDBP mutations can cause the full spectrum of the ALS-FTD continuum. High-throughput sequencing of 18 ALS and FTD genes in an index patient presenting with early-onset pure (behavioral) FTD and a positive family history for ALS revealed an established TARDBP mutation, A382T. This finding demonstrates that a TARDPB mutation can cause early-onset pure FTD without evidence for ALS even in advanced FTD disease stages. Moreover, it indicates that TARDPB screening might be considered even in young patients with "pure" neuropsychiatric disturbances and without evidence of neurodegenerative disease in the parental generation.

Tissue engineering of the anterior cruciate ligament-sodium dodecyl sulfate-acellularized and revitalized tendons are inferior to native tendons.

The acellularization of tendons using detergents (sodium dodecyl sulfate, Triton-X, tri-nitro-butyl-phosphate) is a new source of scaffolds for tissue engineering in anterior cruciate ligament (ACL) repair. In vitro testing demonstrated that acellular tendon scaffolds are biocompatible and show good biomechanical properties, but in vivo confirmation of these results is not yet available. Therefore, the aim of this study was to see in vivo if an acellular allogenic construct colonized with autologous fibroblasts improves the quality of ACL reconstruction. ACL replacement was performed in 31 New Zealand White rabbits using a standardized model. Fifteen animals received autologous semitendinosus tendon, whereas 16 animals were treated with a tissue-engineered construct. This construct was made by acellularization of allogenic semitendinosus tendons using sodium dodecyl sulfate and subsequent in vitro colonization with autologous fibroblasts. Eight weeks postoperatively, macroscopic, biomechanical (ultimate load to failure, elongation, stiffness; n = 8/9), and histological (n = 5) examinations were performed. Biomechanical testing showed decreasing strength of the constructs at 8 weeks after implantation compared with the direct postsurgical strength. However, tissue-engineered constructs (F = 19.7 +/- 20.3 N) were significantly weaker than autologous tendons (F = 61.2 +/- 31.2 N). Histologically, the autologous tendons showed signs of partial necrosis and tissue remodeling. The tissue-engineered constructs exhibited an inflammatory reaction and showed both repopulated and acellular regions. In conclusion, in vivo results were much more unfavorable than in vitro results had suggested. Further studies have to be performed to test if modifications of the acellularization process yield better results in vivo.

Student learning preferences and the impact of a multimedia learning tool in the dissection course at the University of Munich.

How do students use multimedia tools to support their learning during a gross anatomy dissection course? We investigated this question in the anatomic dissection course for first year medical students at the University of Munich (n=850) by giving all participating students access to an anatomical multimedia CD-ROM. The use of this multimedia learning tool was voluntary and it was not essential for the end-of-course examination. After the examination, two questionnaires (return rate first questionnaire n(1)=347, approximately 41%; return rate second questionnaire n(2)=644, approximately 76%) were given to the surveyed students with the following content: evaluation of the multimedia learning tool, details about the usage of different kinds of available learning media, and finally an evaluation of the media used for teaching during the course. Furthermore we collected personal data from participants such as age, gender and the score achieved in the examination. Classical textbooks and anatomical atlases were used by 84% of students for preparation. The multimedia learning tool was used by 34% as an additional media for learning. The multimedia learning tool was not used alone. The data showed differences with regard to gender and performance of students, but not relating to age. Students rated the computer-specific features, e.g. three-dimensional (3D) models, virtual simulations, and an interactive quiz module, as major reasons for using the multimedia learning tool. Our results show that medical students use anatomic multimedia learning tools primarily as an additional medium for learning, and thus lead to the conclusion that the main learning media are still textbooks and anatomic atlases.

Tissue engineering of the anterior cruciate ligament: a new method using acellularized tendon allografts and autologous fibroblasts.

INTRODUCTION: The availability of autogenous tendons (middle part of patellar tendon, semitendinosus/gracilis, or quadriceps tendon) for cruciate ligament reconstructions is restricted and related to withdrawal morbidity. Allografts and synthetic ligament materials often show problems regarding long-term stability and immunological reactions. Therefore, the aim of this study was to develop and characterize a new scaffold based on acellular allografts seeded with autologous cells for tissue engineering of the anterior cruciate ligament (ACL). MATERIALS AND METHODS: Semitendinosus tendons of New Zealand White (NZW) rabbits were harvested and acellularized using the detergent sodium dodecyle sulfate (SDS) as the main ingredient. After that, cultured (37 degrees C, 5% CO(2), medium) dermal fibroblasts were injected into the tendons. These constructs were further cultivated for 4, 7, or 14 days under the same culture conditions. Native, acellular, and seeded tendons underwent biomechanical testing (ultimate load to failure [N], stiffness [N/mm], and elongation [%], each n = 9] and histological hematoxylin-eosin (H.E.) staining. Detailed immunohistochemical (collagen I, III, IV, VI, pro-collagen I, versican, and vimentin) analyses were conducted to detect changes in the composition and structure of the extracellular matrix (ECM) after acellularization. RESULTS: Histologically, a cell-free, crimped slack tendon structure after acellularization and a good integration of the cells after injection (4, 7, and 14 days) were seen. Metabolic activity of the seeded cells was demonstrated by positive immunohistochemical staining for pro-collagen I, which was negative in nonseeded constructs. Major differences in staining patterns of the various other ECM components were not observed. Biomechanically, the maximum load to failure of these tendons was comparable to native tendons (P = 0.429; native 134.5 +/- 12.9 N; acellular 118.5 +/- 7.3 N; seeded 132.3 +/- 5.6 N). Stiffness and elongation were comparable between native and acellular tendons, but differed significantly after seeding (P < 0.001). CONCLUSION: The described method is suitable to make tendons completely cell free without changing their major biomechanical properties. Preservation of the ECM and of the collagen fiber structure by this method should give an ideal environment for autologous cell integration and metabolic activity in contrast to other approaches for tissue acellularization. The cell disruption and extraction of cell detritus should minimize adverse immunogenic reactions.