Promise and challenges of dystonia brain banking: establishing a human tissue repository for studies of X-Linked Dystonia-Parkinsonism.

X-Linked Dystonia-Parkinsonism (XDP) is a neurodegenerative disease affecting individuals with ancestry to the island of Panay in the Philippines. In recent years there has been considerable progress at elucidating the genetic basis of XDP and candidate disease mechanisms in patient-derived cellular models, but the neural substrates that give rise to XDP in vivo are still poorly understood. Previous studies of limited XDP postmortem brain samples have reported a selective dropout of medium spiny neurons within the striatum, although neuroimaging of XDP patients has detected additional abnormalities in multiple brain regions beyond the basal ganglia. Given the need to fully define the CNS structures that are affected in this disease, we created a brain bank in Panay to serve as a tissue resource for detailed studies of XDP-related neuropathology. Here we describe this platform, from donor recruitment and consent to tissue collection, processing, and storage, that was assembled within a predominantly rural region of the Philippines with limited access to medical and laboratory facilities. Thirty-six brains from XDP individuals have been collected over an initial 4 years period. Tissue quality was assessed based on histologic staining of cortex, RNA integrity scores, detection of neuronal transcripts in situ by fluorescent hybridization chain reaction, and western blotting of neuronal and glial proteins. The results indicate that this pipeline preserves tissue integrity to an extent compatible with a range of morphologic, molecular, and biochemical analyses. Thus the algorithms that we developed for working in rural communities may serve as a guide for establishing similar brain banks for other rare diseases in indigenous populations.

To bridge or not to bridge the multisensory time gap: bimanual coordination to sound and touch with temporal lags.

Living in a complex and multisensory environment involves constant interaction between perception and action. There is evidence that multisensory integration is governed by temporal factors, such as physiological synchrony between cross-modal stimuli favouring multisensory benefit, and the existence of a range of asynchrony between the stimuli which affords their binding (the temporal window of integration). These factors were examined in this study in a bimanual sensorimotor synchronization task with cross-modal stimuli. Participants synchronized each hand to a pair of audio-tactile stimuli, in which the asynchrony between onsets of auditory and tactile stimuli was systematically manipulated. In cross-modal conditions, they were instructed to tap either to the auditory stimuli or to tactile stimuli. The results reported a temporal window of integration of 160 ms centred around 40 and 80 ms (tactile first). Moreover, the temporal interval between the auditory and tactile stimuli affected the stability of bimanual coordination and of synchronization exclusively when participants were instructed to synchronize with tactile stimuli. Overall, the results indicate that both physiological asynchrony and temporal window of integration apply to cross-modal integration in a bimanual synchronization task. In addition, it shows the effect of auditory dominance onto multisensory temporal processes. This study sheds light on the role of temporal factors in multisensory processes when perception and actions are rhythmic and coupled.

[Reconciliating neurology and psychiatry: The prototypical case of frontotemporal dementia]. / Rapprochement entre neurologie et psychiatrie : le cas prototypique de la dégénérescence frontotemporale.

Frontotemporal degeneration (FTD) in its behavioral variant (bvFTD) is probably one of the conditions that best illustrates the links between psychiatry and neurology. It is indeed admitted that between a third and half of patients with this condition, especially in early-onset forms, receive an initial diagnosis of psychiatric disorder (depression, schizophrenia, bipolar disorder) and are then referred to a psychiatric ward. BvFTD can thus be considered a neurological disorder with a psychiatric presentation. Among psychiatric symptoms reported in this disease, psychotic symptoms (hallucinations, delusions, especially of persecution), which have long been underestimated in bvFTD and are not part of the current diagnostic criteria, are present in about 20% of cases and may be inaugural. They are particularly common in the genetic forms related to a mutation in the C9orf72 gene (up to 50%), and to a lesser extent in the GRN gene (up to 25%). C9orf72 gene mutation is often associated with a family history of dementia or motor neuron disease but also of psychiatric disorders. It has also been described in sporadic presentation forms. Sometimes, the moderate degree of brain atrophy on MRI described in patients carrying this mutation may complicate the differential diagnosis with late-onset psychiatric diseases. In the present article, we underline the importance of considering that psychiatric - especially psychotic - symptoms are not rare in bvFTD, which should lead to a revision of the diagnostic criteria of this disease by taking greater account of this fact. We also propose a diagnostic chart, based on concerted evaluation by neurologists and psychiatrists for cases of atypical psychiatric symptoms (late-onset or pharmacoresistant troubles) leading to consider the possibility of a neurological disorder, in order to shed a new light on these difficult clinical situations. In the field of research, bvFTD may constitute a model to explore the neural basis of certain psychiatric disorders, and a possible molecular link between bvFTD and psychoses, which could eventually lead to new therapeutic approaches, has been recently suggested. Thus, bvFTD illustrates how the links between neurology and psychiatry are close and tend to evolve with the progress of scientific knowledge. It is necessary to strengthen collaboration between the two disciplines both to improve the care - diagnosis and management of these patients - and to promote the emergence of innovative clinical research.

High-frequency ultrasonography but not 930-nm optical coherence tomography reliably evaluates melanoma thickness in vivo: a prospective validation study.

BACKGROUND: Early diagnosis and rapid surgical excision are essential for improving the prognosis of patients with melanoma. Reflectance confocal microscopy has been validated as a feasible procedure for in vivo diagnosis of melanoma but cannot be used to measure tumour thickness. However, ultrasonography and optical coherence tomography may allow melanoma thickness to be measured in vivo. OBJECTIVES: To validate the accuracy and reliability of high-frequency ultrasonography (HFUS) and optical coherence tomography for assessing melanoma thickness in vivo. METHODS: We conducted a prospective study on 131 patients with at least one equivocal melanocytic lesion. Each lesion underwent optical coherence tomography and HFUS assessment, followed by excision and pathological examination. Histopathology was considered to be the gold standard for assessing melanoma thickness. Repeatability, inter- and intrarater reproducibility and reliability were evaluated for each imaging procedure. RESULTS: Ultrasonography showed a good level of agreement with histology [intraclass correlation coefficient (ICC) 0.807; 95% confidence interval (CI) 0.703-0.877] and excellent inter-rater reproducibility (G = 0.97), resulting in reliable in vivo assessment of melanoma thickness. The 930-nm optical coherence tomography showed a poor level of agreement with histopathology (ICC 0.0; 95% CI -0.2-0.2) and the inter-rater reproducibility was null (G = 0.00). CONCLUSIONS: HFUS is a reliable and reproducible noninvasive method for assessing melanoma thickness. Routine use of HFUS may allow single-step excision of equivocal melanocytic lesions, with surgical margins determined by in vivo assessment of tumour thickness.

A European multicentre reappraisal of distal compound muscle action potential duration in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: The electrodiagnostic value of distal compound muscle action potential duration (DCMAPD) has been studied rarely in chronic inflammatory demyelinating polyneuropathy (CIDP). Cut-offs proposed have not been widely evaluated. The influence of low-cut EMG filter settings ≤ 10 Hz as used in Europe is uncertain. METHODS: We retrospectively reviewed records of 110 patients with typical, treatment-responsive CIDP, from Leicester, U.K., Paris and Angers, France. All fulfilled revised European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) clinical and electrodiagnostic criteria for typical CIDP (2010), before consideration of DCMAPD prolongation. Results were compared with those of 110 controls with chronic sensory/sensory-motor axonal neuropathy. We constructed receiver operating characteristic (ROC) curves for each nerve and derived cut-offs for DCMAPD prolongation, offering specificity of ≥ 98% vs. controls. RESULTS: DCMAPD was significantly greater in all nerves for CIDP patients, compared with controls (P < 0.001). ROC curves allowed derivation of cut-offs of sensitivities ranging from 27.1% (ulnar nerve) to 60% (tibial nerve). Using these cut-offs to define DCMAPD prolongation in any studied motor nerve offered a sensitivity of 69.1% for CIDP and specificity of 97.3% vs. controls. CONCLUSION: Cut-offs for DCMAPD are dependent on EMG filter settings. DCMAPD prolongation in any motor nerve, using our derived cut-offs, represents a sensitive and specific marker of CIDP in patients studied with EMG equipment with low-cut filter settings ≤ 10 Hz. Appropriate use of this parameter appears an essential criterion to consider in assessing suspected CIDP, which may be helpful in limiting extensiveness and duration of electrophysiological testing, thereby reducing patient discomfort.

Interacting humans use forces in specific frequencies to exchange information by touch.

Object-mediated joint action is believed to be enabled by implicit information exchange between interacting individuals using subtle haptic signals within their interaction forces. The characteristics of these haptic signals have, however, remained unclear. Here we analyzed the interaction forces during an empirical dyadic interaction task using Granger-Geweke causality analysis, which allowed us to quantify the causal influence of each individual's forces on their partner's. We observed that the inter-partner influence was not the same at every frequency. Specifically, in the frequency band of [2.15-7] Hz, we observed inter-partner differences of causal influence that were invariant of the movement frequencies in the task and present only when information exchange was indispensable for task performance. Moreover, the inter-partner difference in this frequency band was observed to be correlated with the task performance by the dyad. Our results suggest that forces in the [2.15-7] Hz band constitute task related information exchange between individuals during physical interactions.

Multi-sensory feedback improves spatially compatible sensori-motor responses.

To interact with machines, from computers to cars, we need to monitor multiple sensory stimuli, and respond to them with specific motor actions. It has been shown that our ability to react to a sensory stimulus is dependent on both the stimulus modality, as well as the spatial compatibility of the stimulus and the required response. However, the compatibility effects have been examined for sensory modalities individually, and rarely for scenarios requiring individuals to choose from multiple actions. Here, we compared response time of participants when they had to choose one of several spatially distinct, but compatible, responses to visual, tactile or simultaneous visual and tactile stimuli. We observed that the presence of both tactile and visual stimuli consistently improved the response time relative to when either stimulus was presented alone. While we did not observe a difference in response times of visual and tactile stimuli, the spatial stimulus localization was observed to be faster for visual stimuli compared to tactile stimuli.

A lineage tree-based hidden Markov model quantifies cellular heterogeneity and plasticity.

Individual cells can assume a variety of molecular and phenotypic states and recent studies indicate that cells can rapidly adapt in response to therapeutic stress. Such phenotypic plasticity may confer resistance, but also presents opportunities to identify molecular programs that could be targeted for therapeutic benefit. Approaches to quantify tumor-drug responses typically focus on snapshot, population-level measurements. While informative, these methods lack lineage and temporal information, which are particularly critical for understanding dynamic processes such as cell state switching. As new technologies have become available to measure lineage relationships, modeling approaches will be needed to identify the forms of cell-to-cell heterogeneity present in these data. Here we apply a lineage tree-based adaptation of a hidden Markov model that employs single cell lineages as input to learn the characteristic patterns of phenotypic heterogeneity and state transitions. In benchmarking studies, we demonstrated that the model successfully classifies cells within experimentally-tractable dataset sizes. As an application, we analyzed experimental measurements in cancer and non-cancer cell populations under various treatments. We find evidence of multiple phenotypically distinct states, with considerable heterogeneity and unique drug responses. In total, this framework allows for the flexible modeling of single cell heterogeneity across lineages to quantify, understand, and control cell state switching.

Tissue-specific and repeat length-dependent somatic instability of the X-linked dystonia parkinsonism-associated CCCTCT repeat.

X-linked dystonia-parkinsonism (XDP) is a progressive adult-onset neurodegenerative disorder caused by insertion of a SINE-VNTR-Alu (SVA) retrotransposon in the TAF1 gene. The SVA retrotransposon contains a CCCTCT hexameric repeat tract of variable length, whose length is inversely correlated with age at onset. This places XDP in a broader class of repeat expansion diseases, characterized by the instability of their causative repeat mutations. Here, we observe similar inverse correlations between CCCTCT repeat length with age at onset and age at death and no obvious correlation with disease duration. To gain insight into repeat instability in XDP we performed comprehensive quantitative analyses of somatic instability of the XDP CCCTCT repeat in blood and in seventeen brain regions from affected males. Our findings reveal repeat length-dependent and expansion-based instability of the XDP CCCTCT repeat, with greater levels of expansion in brain than in blood. The brain exhibits regional-specific patterns of instability that are broadly similar across individuals, with cerebellum exhibiting low instability and cortical regions exhibiting relatively high instability. The spectrum of somatic instability in the brain includes a high proportion of moderate repeat length changes of up to 5 repeats, as well as expansions of ~ 20- > 100 repeats and contractions of ~ 20-40 repeats at lower frequencies. Comparison with HTT CAG repeat instability in postmortem Huntington's disease brains reveals similar brain region-specific profiles, indicating common trans-acting factors that contribute to the instability of both repeats. Analyses in XDP brains of expansion of a different SVA-associated CCCTCT located in the LIPG gene, and not known to be disease-associated, reveals repeat length-dependent expansion at overall lower levels relative to the XDP CCCTCT repeat, suggesting that expansion propensity may be modified by local chromatin structure. Together, the data support a role for repeat length-dependent somatic expansion in the process(es) driving the onset of XDP and prompt further investigation into repeat dynamics and the relationship to disease.

[Petrous plasmacytoma revealed by a painful peripheral facial palsy]. / Plasmocytome du rocher révélé par une paralysie faciale périphérique douloureuse.

INTRODUCTION: The classical hypothesis of Bell's palsy, tempting in cases of peripheral facial palsy of rapid onset, must nevertheless be evoked with caution particularly if an intense pain is present, which should lead to search for a tumor of the skull base, especially the petrous bone. CASE REPORT: A 43-year-old man presented a peripheral facial palsy of rapidly progressive onset. A petrous bone tumor was diagnosed on the CT scan, which revealed an aspect of a glomic tumor or a metastatic lesion. The final histological diagnosis was plasmacytoma. DISCUSSION: This type of tumor has been rarely reported in this location. The radiological features are not specific at all, underlying the importance of searching for some associated signs such as a monoclonal protein and performing a histological examination when the firm diagnosis of a systemic disease like multiple myeloma has not been possible.

Human immunodeficiency virus atropy induces modification of subcutaneous adipose tissue architecture: in vivo visualization by high-resolution magnetic resonance imaging.

BACKGROUND: Human immunodeficiency virus (HIV) infection generally induces lipodystrophy. For targeted treatment a better understanding of its development is necessary. The utility of high-resolution magnetic resonance imaging (MRI) is explored. OBJECTIVES: The present study presents a way to visualize the adipose tissue architecture in vivo and to inspect modifications associated with the atrophy. METHODS: High-resolution MRI scans with surface coils were performed on the calf and at the lumbar region of three groups of patients: HIV patients with lipoatrophy, HIV patients without lipoatrophy and healthy volunteers. All patients underwent a clinical examination. In addition, dual energy X-ray absorptiometry (DEXA) measurements were taken. On the MRI scans adipose tissue thickness and adipose nodule size were measured. Results High-resolution MRI enabled identification of a clear disorganization of adipose tissue in patients with lipoatrophy. In addition, these patients presented a very small adipose tissue thickness on the calf and a very small nodule size. RESULTS: led to the hypothesis that adipose tissue disorganization appears before changes in DEXA measurements or clinically visible modifications. CONCLUSIONS: High-resolution MRI enabled visualization in vivo of precise changes in tissue organization due to HIV lipoatrophy. This imaging technique should be very informative for better monitoring of the atrophy.

Quantitative magnetic resonance imaging of subcutaneous adipose tissue.

BACKGROUND/PURPOSE: Quantitative transverse relaxation time (T(2)) magnetic resonance (MR) imaging has been used with the aim to characterize subcutaneous adipose tissue. Protons in adipose tissue have a fast exchange behavior giving bi-component transverse relaxation processes with short and long relaxation time values depending on the tissue properties. METHODS: MR images were acquired on a 1 T Siemens MR scan using a multi-spin-echo sequence. A high sensitive surface coil, enabling low noise MR images with voxel size of 10 mm(3), was used for performing accurate quantitative T(2) imaging. These acquisition parameters were determined by a preliminary study performed on an oil phantom known to be a valuable model for mimicking in vivo adipose tissue. In vivo study of the thigh adipose tissue was carried out on 30 volunteers. 20 women with various clinically diagnosed cellulite grades and 10 males, among them five showed overweight. Tissue characterization was finally performed through the analysis of the T(2) distributions. RESULTS: Phantom study showed that improvements in the precision in T(2) measurement are obtained at the expense of the spatial resolution. Uncertainties in T(2) measurements are three times lower by considering a region of interest of 3 x 3 pixels compared with a pixel by pixel analysis. The in vivo study showed that women groups present higher mean short T(2S) component values than men. Histogram of T(2) distribution showed that the maximum amplitude is observed at a lower value for the overweight men group. In addition, larger values around the septae were visualized on the long relaxation time images. CONCLUSIONS: This study shows that precise T(2) map of adipose tissue can be computed. The balance between precision and spatial resolution is examined. Preliminary results relative to tissue organization and to difference between clinical groups proves the potential of the quantitative MRI.

A multitechnique evaluation of topical corticosteroid treatment.

BACKGROUND/PURPOSE: Corticosteroids are widely prescribed for systemic or local treatment of inflammatory autoimmune disorders. Long-term therapy is associated with side effects and causes cutaneous atrophy of the epidermis and the dermis. The present study aims to evaluate with several noninvasive techniques, the skin modifications observed during corticosteroids treatment. The potential of skin mechanical measurement and ultrasound radio frequency (RF) signal analysis are proposed as new measures more closely related to the functional impairments. METHODS: Thirteen young healthy women volunteers had two applications per day on one arm of topical Clobetasol propionate 0.05% for 28 days, and they were followed for 28 days more. Skin modifications were studied by high-frequency ultrasound imaging, ultrasound RF signal analysis, optical coherence tomography and by the suction test. RESULTS: For all the techniques, a statistically significant change is observed with treatment. Large variations, around 30%, are observed for all techniques, but less for ultrasound imaging (10%). Dermis and epidermis thickness presented stable measurements on the nontreated zone. At the end of the study, measures returned to normal. The dynamic is mainly observed within the first 14 days of treatment and within the first 14 days after its cessation. CONCLUSION: Similar dynamics of skin modification during corticosteroid treatment was observed with very different techniques. Moreover, the potential of RF ultrasound analysis and mechanical skin measurement for characterizing skin structural and functional impairments has been evaluated.

Mutations of the noggin (NOG) and of the activin A type I receptor (ACVR1) genes in a series of twenty-seven French fibrodysplasia ossificans progressiva (FOP) patients.

Fibrodysplasia ossificans progressiva (FOP) is a rare but very severe disease, characterised by congenital malformations of the toes and by progressive heterotopic ossification of muscles and joints. Two genes, the noggin (NOG) gene and the activin A type I receptor (ACVRI) gene, are involved in FOP. In this study we have searched for the NOG and the 617G>A (ACVR1) mutations in a well characterized series of twenty-seven French FOP patients. Five NOG mutations (delta 42, 274G>C, 275G>A, 276G>A, and 283G>A) have been found in seven (26%) of our FOP patients. The 617G>A mutation in the ACVR1 gene is found in fourteen (52%) of the patients. With one exception (patient number 22), 617G>A and NOG mutations are mutually exclusive in patients. Mutations 274G>C, 283G>A and 617G>A segregate with the trait in five different FOP families, some members of them being partially affected by the disease.

A nonlinear elastic behavior to identify the mechanical parameters of human skin in vivo.

BACKGROUND/PURPOSE: Various analyses have been performed to identify the mechanical properties of the human skin tissue in vivo. They generally use different approaches and hypotheses (behavior laws as well as mechanical tests) and the obtained results are consequently difficult to analyze and compare. In this paper, an inverse method that can be adapted to any kind of mechanical tests and behavior laws is presented. METHOD: A suction deformation performed on the volar aspect of the forearm of a subject is considered. This test is modeled with the finite element method to compare the experimental and simulated curves using an inverse method that allows the skin mechanical parameters identification. This process is based on two optimization algorithms, Kalman's filter and Gauss-Newton's methods. To account for the nonlinear behavior of the skin, a specific nonlinear elastic law, which is then compared with standard linear elastic and neo-Hookean's mechanical behaviors, was developed. RESULTS: The obtained results first prove that neither linear elasticity nor neo-Hookean's laws can be used to model the skin. On the contrary, the nonlinear elastic model presents a relevant fit of the experimental curves. The skin thickness is also proved to be another key point to be taken into consideration. CONCLUSIONS: The obtained results are successfully compared with literature and the reliability of the proposed method is underlined with the identification of 300 additional experimental curves. The different works we are currently focusing on are finally introduced.

Validation of a non-contact technique for local skin temperature measurements.

UNLABELLED: Here we propose to quantify local temperature variations using thermal imaging to assess the effect of dermatological lasers. OBJECTIVES: To quantify the temperature raise induced by laser application and to differentiate the effects of a potassium titanyl phosphate (KTP) laser and an intense pulsed light (IPL). METHODS: A randomized comparative study was performed on 10 adult volunteers with symmetrical rosacea treated by KTP laser or IPL. Skin temperature measurements were performed on inclusion, immediately after laser treatment and 3 min after thermal water application, using a high-resolution (0.08 degrees C) infrared thermal video camera. RESULTS: KTP laser treatment induced a significant rise in local skin temperature whereas no significant change was revealed by the IPL treatment. The infrared camera is a reliable and reproducible technique that allows a follow-up of skin temperature without skin contact. CONCLUSION: Thermography using an infrared camera could potentially be applied in clinical pharmacology for inflammatory reactions or scarring processes.

Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer's disease.

Early identification of Alzheimer's disease (AD) risk factors would aid development of interventions to delay the onset of dementia, but current biomarkers are invasive and/or costly to assess. Validated plasma biomarkers would circumvent these challenges. We previously identified the kinase DYRK1A in plasma. To validate DYRK1A as a biomarker for AD diagnosis, we assessed the levels of DYRK1A and the related markers brain-derived neurotrophic factor (BDNF) and homocysteine in two unrelated AD patient cohorts with age-matched controls. Receiver-operating characteristic curves and logistic regression analyses showed that combined assessment of DYRK1A, BDNF and homocysteine has a sensitivity of 0.952, a specificity of 0.889 and an accuracy of 0.933 in testing for AD. The blood levels of these markers provide a diagnosis assessment profile. Combined assessment of these three markers outperforms most of the previous markers and could become a useful substitute to the current panel of AD biomarkers. These results associate a decreased level of DYRK1A with AD and challenge the use of DYRK1A inhibitors in peripheral tissues as treatment. These measures will be useful for diagnosis purposes.

High spatial resolution quantitative MR images: an experimental study of dedicated surface coils.

Measuring spin-spin relaxation times (T2) by quantitative MR imaging represents a potentially efficient tool to evaluate the physicochemical properties of various media. However, noise in MR images is responsible for uncertainties in the determination of T2 relaxation times, which limits the accuracy of parametric tissue analysis. The required signal-to-noise ratio (SNR) depends on the T2 relaxation behaviour specific to each tissue. Thus, we have previously shown that keeping the uncertainty in T2 measurements within a limit of 10% implies that SNR values be greater than 100 and 300 for mono- and biexponential T2 relaxation behaviours, respectively. Noise reduction can be obtained either by increasing the voxel size (i.e., at the expense of spatial resolution) or by using high sensitivity dedicated surface coils (which allows us to increase SNR without deteriorating spatial resolution in an excessive manner). However, surface coil sensitivity is heterogeneous, i.e., it--and hence SNR--decreases with increasing depth, and the more so as the coil radius is smaller. The use of surface coils is therefore limited to the analysis of superficial structure such as the hypodermic tissue analysed here. The aim of this work was to determine the maximum limits of spatial resolution and depth compatible with reliable in vivo T2 quantitative MR images using dedicated surface coils available on various clinical MR scanners. The average thickness of adipose tissue is around 15 mm, and the results obtained have shown that obtaining reliable biexponential relaxation analysis requires a minimum achievable voxel size of 13 mm3 for a conventional volume birdcage coil and only of 1.7 mm3 for the smallest available surface coil (23 mm in diameter). Further improvement in spatial resolution allowing us to detect low details in MR images without deteriorating parametric T2 images can be obtained by image filtering. By using the non-linear selective blurring filter described in a previous work, the voxel size was reduced to 0.8 mm3, allowing us to detect microstructures such as fibrous septae while preserving precision in T2 measurements. This paper provides practical information allowing us to perform reliable T2 quantitative MR micro images. High resolution imaging with dedicated surface coils, which is only well-suited to near surface organs, might lead to highly valuable results in this context, especially to analyse the hypodermis involved in the lipodystrophy seen in patients with human immuno-deficiency virus (HIV).

Image analysis of skin scaling using D-Squame samplers: comparison with clinical scoring and use for assessing moisturizer efficacy.

The severity of scaling disorders can be evaluated objectively using the D-Squame technique coupled with image analysis. The parameters of scaling derived using this approach need to be clinically relevant and should have greater discrimination than visual grading. Improvements to an existing method that fulfil these requirements are presented. Three scaling parameters were calculated using image analysis of digitized video-captured images of obliquely lit D-Squame samples. These parameters were compared to clinical scores of scaling made by five observers from photographs of the same areas sampled with D-Squame. In addition, two clinical studies were carried out to assess moisturizer effects on different degrees of xerosis, and to compare two different moisturizer preparations. The three scaling parameters gave correlation coefficients, r, between 0.6 and 0.75 when compared with global clinical scores of scaling. Significant reductions in all parameters were observed with 2 weeks of moisturizer use on lower leg skin with marked xerosis compared to an untreated control. The same moisturizer had a similar effect on milder xerosis of the forearm, and showed a greater decrease than a moisturizer with lower glycerol content. Increases in skin hydration, as measured with a corneometer, were also seen in both clinical studies, and corresponded well with D-Squame results. Differences in the degrees of scaling between these two anatomical sites were also detected with this technique. In a previous publication, the same technique was shown to be repeatable and reproducible; in the current article its correlation with clinical observations of scaling or flaking skin has been demonstrated.