Intracranial application of free fasciocutaneous flaps in a novel sandwich technique for skull base reconstruction

Free tissue transfer has been the gold standard of extensive skull base reconstruction, but the onlay of free flaps onto skull base defects carries the risk of cerebrospinal fluid (CSF) leakage. The purpose of this study was the evaluation of a novel technique of a combined sub- and onlay concept with a partially intracranially positioned folded free fasciocutaneous flap in terms of flap applicability, versatility and complication rate. Within 5 years, 7 patients with anterior (n=4), middle (n=2) or posterior (n=1) skull base defects were reconstructed with free extended lateral arm (n=3) or anterolateral thigh (n=4) flaps. The flaps were partially intracranially positioned and fixed with osteo-dermal sutures. Both flaps proved to be applicable in terms of sealing efficiency, minimizing intracranial flap volume and folding. No flap loss was observed. Specific complications consisted of one pneumocranium via an accessory frontal sinus and one cerebellar herniation due to lumbar CSF loss. No flap failure or haematoma of the intracranial flap part occurred. This new concept of intracranial positioning of fasciocutaneous flaps in a sandwich technique using osteo-dermal sutures should be considered as a primary treatment for skull base reconstruction rather than merely as a salvage manoeuvre

Revising two-point discrimination assessment in normal aging and in patients with polyneuropathies

Objectives: To revise the static and dynamic normative values for the two-point discrimination test and to examine its applicability and validity in patients with a polyneuropathy. Methods: Two-point discrimination threshold values were assessed in 427 healthy controls and 99 patients mildly affected by a polyneuropathy. The controls were divided into seven age groups ranging from 20-29, 30 39,..., up to 80 years and older; each group consisted of at least 30 men and 30 women. Two-point discrimination examination took place under standardised conditions on the index finger. Correlation studies were performed between the scores obtained and the values derived from the Weinstein Enhanced Sensory Test (WEST) and the arm grade of the Overall Disability SumScore (ODSS) in the patients' group (validity studies). Finally, the sensitivity to detect patients mildly affected by a polyneuropathy was evaluated for static and dynamic assessments. Results: There was a significant age-dependent increase in the two-point discrimination values. No significant gender difference was found. The dynamic threshold values were lower than the static scores. The two-point discrimination values obtained correlated significantly with the arm grade of the ODSS (static values: r = 0.33, p = 0.04; dynamic values: r = 0.37, p = 0.02) and the scores of the WEST in patients (static values: r = 0.58, p = 0.0001; dynamic values: r = 0.55, p = 0.0002). The sensitivity for the static and dynamic threshold values was 28% and 33%, respectively. Conclusion: This study provides age-related normative two-point discrimination threshold values using a two-point discriminator (an aesthesiometer). This easily applicable instrument could be used as part of a more extensive neurological sensory evaluation

Fully defined human pluripotent stem cell-derived microglia and tri-culture system model C3 production in Alzheimer's disease

Aberrant inflammation in the CNS has been implicated as a major player in the pathogenesis of human neurodegenerative disease. We developed a new approach to derive microglia from human pluripotent stem cells (hPSCs) and built a defined hPSC-derived tri-culture system containing pure populations of hPSC-derived microglia, astrocytes, and neurons to dissect cellular cross-talk along the neuroinflammatory axis in vitro. We used the tri-culture system to model neuroinflammation in Alzheimer's disease with hPSCs harboring the APP(SWE)+/+ mutation and their isogenic control. We found that complement C3, a protein that is increased under inflammatory conditions and implicated in synaptic loss, is potentiated in tri-culture and further enhanced in APP(SWE)+/+ tri-cultures due to microglia initiating reciprocal signaling with astrocytes to produce excess C3. Our study defines the major cellular players contributing to increased C3 in Alzheimer's disease and presents a broadly applicable platform to study neuroinflammation in human disease

Revising two-point discrimination assessment in normal aging and in patients with polyneuropathies.

To revise the static and dynamic normative values for the two-point discrimination test and to examine its applicability and validity in patients with a polyneuropathy. Two-point discrimination threshold values were assessed in 427 healthy controls and 99 patients mildly affected by a polyneuropathy. The controls were divided into seven age groups ranging from 20-29, 30-39,..., up to 80 years and older; each group consisted of at least 30 men and 30 women. Two-point discrimination examination took place under standardised conditions on the index finger. Correlation studies were performed between the scores obtained and the values derived from the Weinstein Enhanced Sensory Test (WEST) and the arm grade of the Overall Disability SumScore (ODSS) in the patients' group (validity studies). Finally, the sensitivity to detect patients mildly affected by a polyneuropathy was evaluated for static and dynamic assessments. There was a significant age-dependent increase in the two-point discrimination values. No significant gender difference was found. The dynamic threshold values were lower than the static scores. The two-point discrimination values obtained correlated significantly with the arm grade of the ODSS (static values: r = 0.33, p = 0.04; dynamic values: r = 0.37, p = 0.02) and the scores of the WEST in patients (static values: r = 0.58, p = 0.0001; dynamic values: r = 0.55, p = 0.0002). The sensitivity for the static and dynamic threshold values was 28% and 33%, respectively. This study provides age-related normative two-point discrimination threshold values using a two-point discriminator (an aesthesiometer). This easily applicable instrument could be used as part of a more extensive neurological sensory evaluation