A clinical case-control comparison of epidermal innervation density in Rett syndrome.

INTRODUCTION: Rett syndrome (RTT), a rare neurodevelopmental disorder occurring primarily in females (1:10-15,000 female live births), is most often caused by loss-of-function mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2). Clinical observations and preclinical findings indicate apparent abnormal sensory and nociceptive function. There have been no direct investigations of epidermal sensory innervation in patients with RTT. METHODS: We compared 3 mm epidermal punch biopsy specimens from adolescent female RTT patients (N = 4, aged 12-19 years) against an archived approximate age-, sex-, body-site matched comparison sample of healthy adolescent females (N = 8, ages 11-17). RESULTS: Confocal imaging revealed, on average, statistically significant increased epidermal nerve fiber (ENF) peptidergic (co-stained calcitonin gene-related protein [CGRP]) innervation density compared with healthy female control individuals. CONCLUSIONS: Given the clinical phenotype of disrupted sensory function along with diagnostic criteria specific to cold hands/feet and insensitivity to pain, our preliminary observations of ENF peptidergic fiber density differences warrants further investigation of the peripheral neurobiology in RTT.

Patients' attitudes toward health care providers collecting information about their race and ethnicity.

BACKGROUND: Experts recommend that health care providers (HCPs) collect patients' race/ethnicity, but HCPs worry that this may alienate patients. OBJECTIVE: To determine patients' attitudes toward HCPs collecting race/ethnicity data. DESIGN: Cross-sectional survey. PARTICIPANTS: General Internal Medicine patients (n=220). MEASUREMENTS: Perceived importance of having HCPs collect race/ethnicity data, their concerns about this, comfort level providing this information, and reactions to 4 statements explaining the rationale for collecting this. RESULTS: Approximately 80% somewhat or strongly agreed that HCPs should collect information on patients' race/ethnicity. However, 28% had significant discomfort (score 5 or less on 10-point scale) reporting their own race/ethnicity to a clerk, and 58% were somewhat or very concerned that this information could be used to discriminate against patients. Compared with whites, blacks, and Hispanics felt less strongly that HCPs should collect race/ethnicity data from patients (P=.04 for both pairwise comparisons), and blacks were less comfortable reporting their own race/ethnicity than whites (P=.03). Telling patients that this information would be used for monitoring quality of care improved comfort more than telling patients that the data collected (a) was mandated by others, (b) would be used to guide staff hiring and training, and (c) would be used to ensure the patient got the best care possible. CONCLUSIONS: Most patients think HCPs should collect information about race/ethnicity, but many feel uncomfortable giving this information, especially among minorities. Health care providers can increase patients' comfort levels by telling them this will be used to monitor quality of care.

Peripheral Innervation in Children With Global Developmental Delay: Biomarker for Risk for Self-Injurious Behavior?

The relation between somatosensory mechanisms and self-injury among children with neurologic impairments associated with developmental delay is not well understood. We evaluated the feasibility of procuring skin biopsies to examine epidermal nerve fiber density and reported self-injury. Following informed parental consent, epidermal skin biopsies were obtained from a distal leg site with no pre-existing skin damage from 11 children with global developmental delay (55% male; mean age = 36.8 months, 17-63 months). Visual microscopic examination and quantitative analyses showed extremely high epidermal nerve fiber density values for some children. Children with reported self-injury (5/11) had significantly (P < .02) greater density values (138.8, standard deviation = 45.5) than children without self-injury (80.5, standard deviation = 17.5). Results from this novel immunohistologic analysis of skin in very young children with neurodevelopmental delays suggest it may be a useful tool to study peripheral innervation as a possible sensory risk factor for self-injury.

Variation in quantitative sensory testing and epidermal nerve fiber density in repeated measurements.

Quantitative sensory testing (QST) is commonly used to evaluate peripheral sensory function in neuropathic conditions. QST measures vary in repeated measurements of normal subjects but it is not known whether QST can reflect small changes in epidermal nerve fiber density (ENFd). This study evaluated QST measures (touch, mechanical pain, heat pain and innocuous cold sensations) for differences between genders and over time using ENFd as an objective-independent measure. QST was performed on the thighs of 36 healthy volunteers on four occasions between December and May. ENFd in skin biopsies was determined on three of those visits. Compared to men, women had a higher ENFd, a difference of 12.2 ENFs/mm. They also had lower tactile and innocuous cold thresholds, and detected mechanical pain (pinprick) at a higher frequency. Heat pain thresholds did not differ between genders. By the end of the 24-week study, men and women showed a small reduction (p<0.05) in the frequency of sharp mechanical pain evoked by pinprick whereas tactile and thermal thresholds showed no change. This coincided with a small decrease in ENFd, 4.18 ENFs/mm. Variation in measurements over time was large in a fraction of normal subjects. We conclude that most QST measures detect relatively large differences in epidermal innervation (12.2 ENFs/mm), but response to mechanical pain was the only sensory modality tested with the sensitivity to detect small changes in innervation (4.18 ENFs/mm). Since some individuals had large unsystematic variations, unexpected test results should therefore alert clinicians to test additional locations.

A system for rapidly and accurately collecting patients' race and ethnicity.

OBJECTIVES: We assessed the feasibility of collecting race/ethnicity data from patients using their own preferred racial/ethnic terms. METHODS: The 424 patients described their race/ethnicity using their own categories, and we compared their descriptions with their responses to the questions (1) "Do you consider yourself Latino or Hispanic?" and (2) "Which category best describes your race?" (7 response options in our computer interview). We also determined patients' preferences between the 2 approaches. RESULTS: The proportions of patients who described themselves with 1, 2, 3, or 4 terms were 46%, 33%, 14%, and 6%, respectively; 2 said only "American" (1%,) and 1 refused to answer (0.5%). The average completion time was 37 +/- 17 seconds. Rates of missing values and categorization as "other" race were lower than with the closed questions. Agreement between racial/ethnic categorization with open-ended and closed responses was 93% (kappa =0.88). Latino/Hispanic and multiracial/multiethnic individuals were more likely to prefer using their own categories to describe their race/ethnicity. CONCLUSIONS: Collecting race/ethnicity data using patients' own racial/ethnic categories is feasible with the use of computerized systems to capture verbatim responses and results in lower rates of missing and unusable data than do standard questions.