Robert O. Kenet

Teledermoscopy - results of a multicentre study on 43 pigmented skin lesions

We performed a multicentre study to evaluate the agreement between the direct clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions. Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11 melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines, two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11 colleagues (six dermatologists, two residents in dermatology, one oncologist, one specialist in internal medicine and one general practitioner) in 10 centres. These 11 colleagues had different degrees of experience in dermoscopy. With histopathology as the gold standard, an average of 85% of the telediagnoses were correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by an expert dermatologist was correct in 91% of cases. The kappa value for all participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy can be a reliable technique for the diagnosis of pigmented skin lesions but one that will depend on the expertise of the observer.

Analysis of heart rate and respiratory patterns in sudden infant death syndrome victims and control infants

ABSTRACT. Retrospective analyses of patterns of breathing and heart rate variability obtained by visual inspection and spectral analysis of ECG and respiratory activity have provided markers associated with subsequent death in a referred population of infants at high risk for sudden infant death syndrome (SIDS). Such markers include breathing patterns characterized by excessive apneic pauses and periodic breathing, heart rate spectra characterized by increased low frequency oscillations, and respiratory activity spectra characterized by a widened “bandwidth” during regular breathing. To test whether such measurements could distinguish SIDS cases and randomly selected controls from a population study the data from 10 cases and 100 age-matched control subjects were analyzed blind. The code was disclosed after completion of the analysis. We found that none of the markers served to distinguish the SIDS cases from the controls in the population at large. This observation may indicate important physiological differences between infants destined to die in the referred high risk population and infants who die of SIDS at large. The possible reasons for our inability to identify the group of SIDS in the general population, as compared to the group of deaths in the referred high risk group are: (1) different disease processes in the two groups, (2) difference responses to the same disease process in the two groups, (3) a response reflecting the psychosocial setting of the referred high risk population, (4) methodological differences between this and previous studies. We conclude that these markers are not of value in screening the population at large.

Neurodegenerative disease phenotypes in carriers of MAPT p.A152T, a risk factor for frontotemporal dementia spectrum disorders and Alzheimer disease.

Recently, Coppola and colleagues demonstrated that a rare microtubule-associated protein tau (MAPT) sequence variant, c.454G>A (p.A152T) significantly increases the risk of frontotemporal dementia (FTD) spectrum disorders and Alzheimer disease (AD) in a screen of 15,369 subjects. We describe clinical features of 9 patients with neurodegenerative disease (4 women) harboring p.A152T, aged 51 to 79 years at symptom onset. Seven developed FTD spectrum clinical syndromes, including progressive supranuclear palsy syndrome (n=2), behavioral variant FTD (bvFTD, n=1), nonfluent variant primary progressive aphasia (nfvPPA, n=2), and corticobasal syndrome (n=2); 2 patients were diagnosed with clinical AD. Thus, MAPT p.A152T is associated with a variety of FTD spectrum clinical presentations, although patients with clinical AD are also identified. These data warrant larger studies with clinicopathologic correlation to elucidate the influence of this genetic variant on neurodegenerative disease.

The advantages of frontotemporal degeneration drug development (part 2 of frontotemporal degeneration: The next therapeutic frontier)

Frontotemporal degeneration (FTD) encompasses a spectrum of related neurodegenerative disorders with behavioral, language, and motor phenotypes for which there are currently no effective therapies. This is the second of two articles that summarize the presentations and discussions that occurred at two symposia in 2011 sponsored by the Frontotemporal Degeneration Treatment Study Group, a collaborative group of academic and industry researchers that is devoted to developing treatments for FTD. This article discusses the current status of FTD clinical research that is relevant to the conduct of clinical trials, and why FTD research may be an attractive pathway for developing therapies for neurodegenerative disorders. The clinical and molecular features of FTD, including rapid disease progression and relatively pure molecular pathology, suggest that there are advantages to developing drugs for FTD as compared with other dementias. FTD qualifies as orphan indication, providing additional advantages for drug development. Two recent sets of consensus diagnostic criteria will facilitate the identification of patients with FTD, and a variety of neuropsychological, functional, and behavioral scales have been shown to be sensitive to disease progression. Moreover, quantitative neuroimaging measurements demonstrate progressive brain atrophy in FTD at rates that may surpass Alzheimers disease. Finally, the similarities between FTD and other neurodegenerative diseases with drug development efforts already underway suggest that FTD researchers will be able to draw on this experience to create a road map for FTD drug development. We conclude that FTD research has reached sufficient maturity to pursue clinical development of specific FTD therapies.

Risk stratification. A practical approach to using epiluminescence microscopy/dermoscopy in melanoma screening.

Risk stratification of pigmented lesions during melanoma screening is a method of classifying lesions into groups based on their relative risk of being melanoma. Risk stratification accepts the fact that clinical examination with and without ELM is not perfect but uses potential ELM clues to early melanoma to increase the sensitivity of screening. Risk stratification permits the use of all available a priori clinical information and the physicians judgement in making a final management decision for each lesion and for each patient. Risk stratification using ELM is based on two primary concepts: (1) a pigment network suggests a lesion is melanocytic and (2) melanoma causes the network to develop heterogeneous (i.e., irregular) and eccentric (i.e., not centered) pigmentation. In applying ELM risk stratification to melanoma screening the physician follows these four steps: 1. Inspect each lesion carefully for a pigment network. 2. If a pigment network is seen, group lesions by their relative degrees of heterogeneity and eccentricity of the pigment network. 3. If a network is not seen, look for typical patterns of benign lesions and melanoma mimickers. 4. Use the resulting clinical risk class to guide management using all available clinical information combined with clinical judgment.

PROSPECTIVE ANALYSIS OF HEART RATE AND BREATHING PATTERNS IN INFANTS SUCCUMBING TO SIDS AND IN CONTROLS

In studies of babies at high risk for SIDS (near-SIDS and siblings), we have identified among some who died excess periodic breathing (PB) excess variability (var) of respiratory frequency (f) and increased oscillation of heart rate (HR), at 4-7 cycles per min., (low frequency peak-LFP). The present study was planned to test the hypothesis that in an unselected prospectively studied population, these same variables might discriminate SIDS from controls. From 6914 term infants, we selected 24 hour pneumograms performed at 6 weeks on 11 SIDS and 101 random controls. One SIDS had one near-SIDS spell. Casettes were coded for blind analysis. From data recorded between 12MN and 6AM we transcribed ECG and respiratory signals onto hard copy for visual inspection and we transferred these signals during all 5 min epochs of quiet breathing (Q) onto FM tape for spectral analysis. We inspected hard copies for PB and apnea ⩾10s. Spectral analysis identified f and var, HR and var and power at f (resp. sinus arrhythmia) and at the LFP. We rank ordered results to test hypothesis 1) that PB and 2) that abnormal spectral var were markers for SIDS. We performed cluster analysis on each data set The code was then broken; neither hypothesis was correct. These results neither support nor negate the apnea hypothesis of SIDS.