Are We Missing Something? The Skin Lesions Not Seen in Teledermatology

Background The suspected skin cancer electronic referral pathway was introduced in 2017. It requires general practitioners to add regional, close-up, and dermoscopic images to a lesion-specific referral template for a teledermatologist to review and advise on management. The virtual lesion clinic is a nurse-led clinic used since 2010 to obtain high-quality images for teledermoscopy assessment. A limitation of both services is the absence of a full-body examination. Objective This study aims to evaluate the number of skin cancers missed during teledermatology assessment. Methods This is a retrospective review of skin lesion referrals to dermatology. Suspected skin cancer referrals made in the latter half of 2020 were compared with referrals to the virtual lesion clinic during a similar time period in 2016. Results The study included 481 patients with 548 lesions in the 2020 suspected skin cancer cohort that were matched for age, sex, and ethnicity to 400 patients with 682 lesions in the 2016 virtual lesion clinic cohort. A total of 41 patients underwent subsequent specialist review in the suspected skin cancer cohort compared to 91 in the virtual lesion clinic cohort. A total of 20% of the suspected skin cancer cohort and 24% of the virtual lesion clinic cohort were found to have at least one additional lesion of concern. The majority of these were keratinocytic skin cancers; there were 2 and 0 additional melanomas or melanoma-in-situ, respectively. The virtual lesion clinic nurses identified additional lesions for imaging in 78 of 400 (20%) patients assessed in the virtual lesion clinic. The teledermatologist determined (author AO) that 73% of these additional lesions were malignant. Of the 548 lesions, 10 (2%) in the suspected skin cancer group were rereferred, none of which had a change in diagnosis. Out of 682 lesions, 16 (2%) in the virtual lesion clinic cohort were rereferred, 6 (1%) of which had a change in diagnosis. Conclusions Patients diagnosed with skin cancer often have multiple lesions of concern. Single-lesion teledermoscopy diagnoses have high concordance with in-person evaluation and histology; however, we have shown that in-person examination may reveal other suspicious lesions. The importance of a full-body skin examination should be emphasized to the referrer. Acknowledgments The Waikato Medical Research Foundation provided financial support for the study. Conflicts of Interest None declared.

Are We Missing Something? The Skin Lesions Not Seen in Teledermatology (Preprint)

BACKGROUND The suspected skin cancer electronic referral pathway was introduced in 2017. It requires general practitioners to add regional, close-up, and dermoscopic images to a lesion-specific referral template for a teledermatologist to review and advise on management. The virtual lesion clinic is a nurse-led clinic used since 2010 to obtain high-quality images for teledermoscopy assessment. A limitation of both services is the absence of a full-body examination. OBJECTIVE This study aims to evaluate the number of skin cancers missed during teledermatology assessment. METHODS This is a retrospective review of skin lesion referrals to dermatology. Suspected skin cancer referrals made in the latter half of 2020 were compared with referrals to the virtual lesion clinic during a similar time period in 2016. RESULTS The study included 481 patients with 548 lesions in the 2020 suspected skin cancer cohort that were matched for age, sex, and ethnicity to 400 patients with 682 lesions in the 2016 virtual lesion clinic cohort. A total of 41 patients underwent subsequent specialist review in the suspected skin cancer cohort compared to 91 in the virtual lesion clinic cohort. A total of 20% of the suspected skin cancer cohort and 24% of the virtual lesion clinic cohort were found to have at least one additional lesion of concern. The majority of these were keratinocytic skin cancers; there were 2 and 0 additional melanomas or melanoma-in-situ, respectively. The virtual lesion clinic nurses identified additional lesions for imaging in 78 of 400 (20%) patients assessed in the virtual lesion clinic. The teledermatologist determined (author AO) that 73% of these additional lesions were malignant. Of the 548 lesions, 10 (2%) in the suspected skin cancer group were rereferred, none of which had a change in diagnosis. Out of 682 lesions, 16 (2%) in the virtual lesion clinic cohort were rereferred, 6 (1%) of which had a change in diagnosis. CONCLUSIONS Patients diagnosed with skin cancer often have multiple lesions of concern. Single-lesion teledermoscopy diagnoses have high concordance with in-person evaluation and histology; however, we have shown that in-person examination may reveal other suspicious lesions. The importance of a full-body skin examination should be emphasized to the referrer.

Remote Skin Cancer Diagnosis: Adding Images to Electronic Referrals Is More Efficient Than Wait-Listing for a Nurse-Led Imaging Clinic

We undertook a retrospective comparison of two teledermatology pathways that provide diagnostic and management advice for suspected skin cancers, to evaluate the time from referral to diagnosis and its concordance with histology. Primary Care doctors could refer patients to either the Virtual Lesion Clinic (VLC), a nurse-led community teledermoscopy clinic or, more recently, to the Suspected Skin Cancer (SSC) pathway, which requires them to attach regional, close-up, and dermoscopic images. The primary objective of this study was to determine the comparative time course between the SSC pathway and VLC. Secondary objectives included comparative diagnostic concordance, skin lesion classification, and evaluation of missed skin lesions during subsequent follow-up. VLC referrals from July to December 2016 and 2020 were compared to SSC referrals from July to December 2020. 408 patients with 682 lesions in the VLC cohort were compared with 480 patients with 548 lesions from the 2020 SSC cohort, matched for age, sex, and ethnicity, including histology where available. Median time (SD) from referral to receipt of teledermatology advice was four (2.8) days and 50 (43.0) days for the SSC and VLC cohorts, respectively (p < 0.001). Diagnostic concordance between teledermatologist and histopathologist for benign versus malignant lesions was 70% for 114 lesions in the SSC cohort, comparable to the VLC cohort (71% of 122 lesions). Referrals from primary care, where skin lesions were imaged with variable devices and quality resulted in faster specialist advice with similar diagnostic performance compared to high-quality imaging at nurse-led specialist dermoscopy clinics.

Human Premotor Corticospinal Projections Are Engaged in Motor Preparation at Discrete Time Intervals: A TMS-Induced Virtual Lesion Study

Objectives: The significance of pre-motor (PMC) corticospinal projections in a frontoparietal motor network remains elusive. Temporal activation patterns can provide valuable information about a region's engagement in a hierarchical network. Navigated transcranial magnetic stimulation (nTMS)-induced virtual lesions provide an excellent method to study cortical physiology by disrupting ongoing activity at high temporal resolution and anatomical precision. We use nTMS-induced virtual lesions applied during an established behavioral task demanding pre-motor activation to clarify the temporal activation pattern of pre-motor corticospinal projections.Materials and Methods: Ten healthy volunteers participated in the experiment (4 female, mean age 24 ± 2 years, 1 left-handed). NTMS was used to map Brodmann areae 4 and 6 for primary motor (M1) and PMC corticospinal projections. We then determined the stimulator output intensity required to elicit a 1 mV motor evoked potential (1 mV-MT) through M1 nTMS. TMS pulse were randomly delivered at distinct time intervals (40, 60, 80, 100, 120, and 140 ms) at 1 mV-MT intensity to M1, PMC and the DLPFC (dorsolateral pre-frontal cortex; control condition) before participants had to perform major changes of their trajectory of movement during a tracing task. Each participant performed six trials (20 runs per trial). Task performance and contribution of regions under investigation was quantified through calculating the tracing error induced by the stimulation.Results: A pre-motor stimulation hotspot could be identified in all participants (16.3 ± 1.7 mm medial, 18.6 ± 1.4 mm anterior to the M1 hotspot). NTMS over studied regions significantly affected task performance at discrete time intervals (F(10, 80) = 3.25, p = 0.001). NTMS applied over PMC 120 and 140 ms before changes in movement trajectory impaired task performance significantly more than when applied over M1 (p = 0.021 and p = 0.003) or DLPFC (p = 0.017 and p &lt; 0.001). Stimulation intensity did not account for error size (β = −0.0074, p = 1).Conclusions: We provide novel evidence that the role of pre-motor corticospinal projections extends beyond that of simple corticospinal motor output. Their activation is crucial for task performance early in the stage of motor preparation suggesting a significant role in shaping voluntary movement. Temporal patterns of human pre-motor activation are similar to that observed in intracortical electrophysiological studies in primates.

Transcranial magnetic stimulation in cognitive neuroscience: Methodological basis and safety

Transcranial magnetic stimulation (TMS) is an intensively developing method of non-invasive brain stimulation. TMS is widely used in cognitive neuroscience to study the causal role of various cortical areas in visual perception, memory, attention, speech, and other cognitive functions. The article discusses the general principles and main directions of TMS applications in cognitive research as well as the modern aspects of using online TMS protocols for the creation of a temporary “virtual lesion”, functional brain mapping, and chronometric studies. Possible applications of offline TMS protocols for long-term modulation of the stimulated cortical area activity are also discussed. Methodological features of TMS studies, including targeting methods, as well as the frequency and intensity of stimulation, are highlighted. The article also describes the possibilities of combining TMS with other methods. Finally, the safety aspects of TMS in healthy subjects in the context of cognitive studies are discussed

Disconnectome Associated with Progressive Ischemic Periventricular White Matter Lesions

Periventricular white matter (PVWM) hyperintensities on T2-weighted MRI are ubiquitous in older adults and associated with dementia. Efforts to determine how PVWM lesions impact structural connectivity to impinge on brain function remain challenging in part because white matter tractography algorithms for diffusion tensor imaging (DTI) may lose fidelity in the presence of lesions. We used a “virtual lesion” approach to characterize the “disconnectome” associated with periventricular white matter (PVWM) lesions. We simulated progressive ischemic PVWM lesions using sub-threshold cerebral blood flow (CBF) masks derived from a previously published group-averaged map acquired from N=436 middle aged subjects in which the lowest CBF values were seen in PVWM and morphologically recapitulated the spatial pattern of PVWM hyperintensities seen in typical aging. We mimicked the age-dependent evolution of PVWM lesion burden by varying the threshold applied to the CBF map. We found that the optic radiations, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, corpus callosum, temporopontine tract and fornix were affected in early simulated PVWM lesion burdens, and that the connectivity of subcortical, cerebellar, and visual regions were significantly disrupted with increasing simulated PVWM lesion burdens. We also validated the use of virtual lesions to simulate the disconnectome due to WM hyperintensities in a cognitively normal elderly cohort (N=46) by evaluating correlations between structural and functional connectomes. The virtual lesion approach provides new insights into the spatial-temporal changes of the brain structural connectome under progressive PVWM burdens during normal aging.Significance StatementWe determined the disconnectomes caused by periventricular white matter (PVWM) lesions using the “virtual lesion” approach. We validated the approach using lesions, DTI and resting-state fMRI data from elderly subjects. We simulated disconnectome of progressive PVWM lesions using cerebral blood flow (CBF) masks in PVWM region with normative DTI data, which provides specificity for an ischemic mechanism and begins to address the possibility that connectivity may be affected by reduced CBF prior to the development of overt lesions on T2-weighted FLAIR MRI. The current study presented new insights into the spatial-temporal evolutions of the brain structural connectome under progressive PVWM burdens under normal aging.

Enhancing vs. inhibiting semantic performance with repetitive transcranial magnetic stimulation over the anterior temporal lobe: frequency- and task- specific effects

Accumulating, converging evidence indicates that the anterior temporal lobe (ATL) appears to be the transmodal hub for semantic representation. A series of repetitive transcranial magnetic stimulation (rTMS) investigations utilizing the ‘virtual lesion’ approach have established the brain-behavioural relationship between the ATL and semantic processing by demonstrating that inhibitory rTMS over the ATL induced impairments in semantic performance in healthy individuals. However, a growing body of rTMS studies suggest that rTMS might also be a tool for cognitive enhancement and rehabilitation, though there has been no previous exploration in semantic cognition. Here, we explored a potential role of rTMS in enhancing and inhibiting semantic performance with contrastive rTMS protocols (1Hz vs. 20Hz) by controlling practice effects. Our results demonstrated that it is possible to modulate semantic performance positively or negatively depending on the ATL stimulation frequency: 20Hz rTMS was optimal for facilitating cortical processing (faster RT in a semantic task) contrasting with diminished semantic performance after 1Hz rTMS. In addition to cementing the importance of the ATL to semantic representation, our findings suggest that 20Hz rTMS leads to semantic enhancement in healthy individuals and potentially could be used for patients with semantic impairments as a therapeutic tool.

Sensorimotor expectations bias motor resonance during observation of object lifting: The causal role of pSTS

Transcranial magnetic stimulation (TMS) studies have highlighted that corticospinal excitability (CSE) is increased during observation of object lifting, an effect termed ‘motor resonance’. This facilitation is driven by movement features indicative of object weight, such as object size or observed movement kinematics. Here, we investigated in 35 humans (23 females) how motor resonance is altered when the observer’s weight expectations, based on visual information, do not match the actual object weight as revealed by the observed movement kinematics. Our results highlight that motor resonance is not robustly driven by object weight but easily masked by a suppressive mechanism reflecting the correctness of the weight expectations. Subsequently, we investigated in 24 humans (14 females) whether this suppressive mechanism was driven by higher-order cortical areas. For this, we induced ‘virtual lesions’ to either the posterior superior temporal sulcus (pSTS) or dorsolateral prefrontal cortex (DLPFC) prior to having participants perform the task. Importantly, virtual lesion of pSTS eradicated this suppressive mechanism and restored object weight-driven motor resonance. In addition, DLPFC virtual lesion eradicated any modulation of motor resonance. This indicates that motor resonance is heavily mediated by top-down inputs from both pSTS and DLPFC. Altogether, these findings shed new light on the theorized cortical network driving motor resonance. That is, our findings highlight that motor resonance is not only driven by the putative human mirror neuron network consisting of the primary motor and premotor cortices as well as the anterior intraparietal sulcus, but also by top-down input from pSTS and DLPFC.Significance StatementObservation of object lifting activates the observer’s motor system in a weight-specific fashion: Corticospinal excitability is larger when observing lifts of heavy objects compared to light ones. Interestingly, here we demonstrate that this weight-driven modulation of corticospinal excitability is easily suppressed by the observer’s expectations about object weight and that this suppression is mediated by the posterior superior temporal sulcus. Thus, our findings show that modulation of corticospinal excitability during observed object lifting is not robust but easily altered by top-down cognitive processes. Finally, our results also indicate how cortical inputs, originating remotely from motor pathways and processing action observation, overlap with bottom-up motor resonance effects.