The Myasthenia Gravis-specific Activities of Daily Living scale as a useful outcome measure and in routine clinical management in Polish patients

Introduction

The Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) is a short, and easy to use disease-specific quality of life during daily routine tool in myasthenia gravis.

Delivery of adipose‐derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration

Introduction: Peripheral nerve damage is associated with high long‐term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose‐derived stem cells (ASC) represents a promising therapeutic modality. Methods: Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical‐sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. Results: On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. Discussion: Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve 58 : 251–260, 2018     

Prefrontal cortex contributions to episodic retrieval monitoring and evaluation

Although the prefrontal cortex (PFC) plays roles in episodic memory judgments, the specific processes it supports are not understood fully. Event-related potential (ERP) studies of episodic retrieval have revealed an electrophysiological modulation – the right-frontal ERP old/new effect – which is thought to reflect activity in PFC. The functional significance of this old/new effect remains a matter of debate, and this study was designed to test two accounts: (i) that the effect indexes processes linked to the monitoring or evaluation of the products of retrieval in service of task demands, or (ii) that it indexes the number of internal decisions required for a task judgment. Participants studied words in one of two colours. In a subsequent retrieval task, old (studied) and new words were presented in a neutral colour. Participants made initial old/new judgments, along with study colour judgments to words thought to be old. They also indicated their confidence (high/low) in the colour decision. Right-frontal ERP old/new effects were larger for high than for low confidence correct colour judgments, and the magnitude of the right-frontal effect was correlated with the proportions of low confidence judgments that were made. Because the numbers of decisions associated with these response categories are equivalent, these findings do not support a decision-based account of the right-frontal ERP old/new effect. Rather, the correlation between confidence and the magnitude of the effect links it with retrieval monitoring and evaluation processes.     

Lamina-specific changes in hippocampal GABAA/cBZR and mossy fibre sprouting during and following amygdala kindling in the rat

Alterations in hippocampal GABA_A/central benzodiazepine receptor (GABA_A/cBZR) expression and mossy fibre sprouting (MFS) may have aetiological significance in temporal lobe epileptogenesis. Their relationship with each other is also unknown. We utilised [³H]-flumazenil autoradiography to quantify changes in GABA_A/cBZR density and affinity in all hippocampal laminae, and Timm's staining for MFS at different stages of epileptogenesis in the amygdala kindling rat model (after 24 stimulations, 48 stimulations and two weeks post-kindling). During kindling, receptor density was significantly elevated within the dentate stratum moleculare and granulosum, but decreased within the stratum radiatum of CA3 and CA2. Two weeks post-kindling, receptor density remained upregulated in the dentate stratum moleculare and was also upregulated in CA3 stratum oriens and CA1 stratum moleculare. MFS was significantly increased in the dentate stratum moleculare at two weeks post-kindling, with a strong inverse correlation between MFS and GABA_A/cBZR density in this region. No changes in GABA_A/cBZR binding affinity were detected for any hippocampal subregion at any time point. Our results demonstrate that changes in hippocampal GABA_A/cBZR expression are lamina- and time-specific. Within the dentate gyrus, receptor density is upregulated throughout epileptogenesis, whilst within the hippocampus proper, receptor density is downregulated early in epileptogenesis but upregulated at the chronic phase. A novel association between MFS and GABA_A/cBZR density has been demonstrated by this study, which could represent an important compensatory or pathological mechanism associated with epileptogenesis.     

Association of ictal aphasia with hypoperfusion in language areas in temporal lobe epilepsy patients

Ictal clinical phenomenology, including aphasia, is usually associated with increased regional cerebral perfusion. We present an unusual pattern of ictal cerebral perfusion in three patients with pharmacoresistant, lesional temporal lobe epilepsy and ictal/postictal aphasia studied with prolonged video-EEG, ictal, and interictal SPECT and MRI for pre-surgical evaluation. Subtraction of ictal-interictal SPECT images co-registered with MRI (SISCOM) showed ictal hyperperfusion in the temporal epileptogenic area in all patients. In addition, hypoperfusion of Broca's area in one case, Wernicke's area in other patient, and both areas in the remaining one were observed. Ictal aphasia in these patients may be explained by functional inhibition of a primary language area, driven by the epileptogenic network. This pattern can contribute to understand the pathophysiology of some ictal signs, with an impact on the evaluation of individual surgical risks.     

Invasive squamous cell carcinoma arising in refractory perianal Bowen's disease in a HIV-positive individual

A 54-year-old HIV-positive homosexual man presented with erythematous and pigmented plaques on background erythema in the perianal region, histologically consistent with Bowen's disease. Perianal Bowen's disease represents high-grade anal intraepithelial neoplasia, which is considered a precursor lesion of invasive anal squamous cell carcinoma. This patient's anal intraepithelial neoplasia was unresponsive to multiple treatment modalities including cryotherapy, serial curettage and cautery, topical 5-fluorouracil and 5-aminolaevulinic acid photodynamic therapy. He progressed to develop a poorly differentiated squamous cell carcinoma of the anus three and a half years after the Bowen's disease was diagnosed. The squamous cell carcinoma was treated with combined chemoradiation. A recurrence of high-grade anal intraepithelial neoplasia was noted 6 months after completion of chemoradiation.     

Wound healing is defective in mice lacking tetraspanin CD151

The tetraspanin CD151 forms complexes in epithelial cell membranes with laminin-binding integrins alpha6beta4, alpha3beta1, and alpha6beta1, and modifies integrin-mediated cell migration in vitro. We demonstrate in this study that CD151 expression is upregulated in a distinct temporal and spatial pattern during wound healing, particularly in the migrating epidermal tongue at the wound edge, suggesting a role for CD151 in keratinocyte migration. We show that healing is significantly impaired in CD151-null mice, with wounds gaping wider at 7 days post-injury. The rate of re-epithelialization of the CD151-null wounds is adversely affected, with significantly less wound area being covered by migrating epidermal cells. Our studies reveal that although laminin levels are similar in wild-type and CD151-null wounds, the organization of the laminin in the basement membrane is impaired. Furthermore, upregulation of alpha6 and beta4 integrin expression is adversely affected in CD151-null mice wounds. In contrast, we find no significant effect of CD151 gene knockout on alpha3 and beta1 integrin expression in wound repair. We suggest that mice lacking the CD151 gene are defective in wound healing, primarily owing to impairment of the re-epithelialization process. This may be due to defective basement membrane formation and epithelial cell adhesion and migration.