Beverly Diamond

Osteoporosis in a North American adult population with celiac disease

OBJECTIVE:Osteoporosis, common in European and South American adults with celiac disease, has not been reported in those patients with celiac disease residing in North America. We therefore evaluated bone density in a group of patients from the United States.METHODS:Patients (105 women and 23 men) with celiac disease, who had completed a questionnaire and had bone mineral density (BMD) measured by dual energy x-ray absorptiometry, were evaluated. The patients were an average age of 56 yr old (range 21–83 yr) and had been on a gluten-free diet from 0 months to 46 yr (mean 7.5 yr).RESULTS:Osteoporosis (T score <−2.5) was present in 34% of the patients at the lumbar spine, 27% at the femoral neck, and 36% at the radius. Low bone mass (T score between −1.0 and −2.5) was present in 38% at the lumbar spine, 44% at the femoral neck, and 32% at the radius. When compared to age-matched controls, men were more severely affected than women. BMD did not differ between those on a gluten-free diet and those who had not begun therapy. BMD was remeasured 16 ± 2 months after beginning a gluten-free diet in 5 patients; it increased by 7.5% at the femoral neck (p < 0.02). In 16 patients who had followed a gluten-free diet for an average of 12 yr, BMD remained stable over an additional 2 yr of observation.CONCLUSIONS:Osteoporosis and low bone mass often affect North American adults with celiac disease, whether or not they are on dietary therapy. Routine screening for osteoporosis is indicated in patients with celiac disease.

Supraglottic and Pharyngeal Sensory Abnormalities in Stroke Patients with Dysphagia

Dysphagia and aspiration are two devastating sequelae of stroke, accounting for nearly 40,000 deaths from aspiration pneumonia each year in the United States. While motor deficits in the larynx and pharynx are thought responsible for dysphagia and aspiration in stroke patients, no prior study has evaluated whether these patients also have sensory deficits. The aim of this study was to evaluate the sensory capacity of the laryngopharynx (LP) in supratentorial or brain stem stroke patients who presented with dysphagia. Fifteen stroke patients (mean age, 66.7 ± 13.8 [SD] years) were prospectively evaluated by means of our previously described method whereby air pulse stimuli were delivered via a flexible fiberoptic telescope to the mucosa innervated by the superior laryngeal nerve. There were 15 age-matched controls. No LP sensory deficits were found in any of the age-matched controls. In all stroke patients studied, either unilateral (n = 9) or bilateral (n=6) sensory deficits were identified. Deficits were defined as either a moderate impairment in sensory discrimination thresholds (3.5 to 6.0 mm Hg) or a severe sensory impairment (>6.0 mm Hg). These sensory discrimination thresholds were significantly greater than in age-matched controls (7.05 ± 0.17 mm Hg for the supratentorial group and 6.05 ± 1.22 mm Hg for the infratentorial group versus 2.61 ± 0.69 mm Hg for the controls). Among patients with unilateral deficits, sensory thresholds were moderately to severely elevated in all 9 cases on the affected side compared with the unaffected side (p < .01, Fishers exact test). Moreover, the sensory thresholds of the unaffected side were not significantly different from those of age-matched controls (2.51 ± 0.25 mm Hg versus 2.61 ± 0.69 mm Hg, respectively). All 6 patients with bilateral deficits had severe impairments. The results of an outcome assessment in 13 of 15 patients revealed that 2 out of 5 patients with moderate LP sensory impairment and 5 out of 8 with severe impairment developed aspiration. Our results show for the first time that stroke patients with dysphagia have significant sensory deficits in the LP and that these impairments are likely to contribute to the development of aspiration.

Changing Presentation of Adult Celiac Disease

The mode of presentation of celiac disease in the United States is not known. We investigated the demographic and clinical features of 227 patients with biopsy-proven celiac disease and determined if there had been changes over time. The patients had been entered into a database; those seen prior to 1990 were retrospectively entered while those seen subsequently were prospectively entered. A “symptomatic” presentation described the “classical” presentation of celiac disease with prominent gastrointestinal symptoms: diarrhea and weight loss. Females were younger and had a longer duration of symptoms compared to males. The modes of presentation were symptomatic (62%), anemia or reduced bone density (15%), screening first-degree relatives (13%), and incidental diagnosis at endoscopy (8%). We compared those diagnosed before and after 1993 (when serologic testing was first used), and noted a reduction in those presenting with diarrhea, 73% vs 43% (P = 0.0001) and a reduction in the duration of symptoms, from 9.0 ± 1.1 years to 4.4 ± 0.6 years (P < 0001). In conclusion, the percentage of celiac disease patients presenting with diarrhea has decreased, probably related to the more widespread use of serologic testing for celiac disease.

Age-Related Changes in Pharyngeal and Supraglottic Sensation

As one ages, sensory discrimination in the oral cavity progressively diminishes, and dysphagia and aspiration are more likely to occur. Whether similar age-related laryngeal and pharyngeal sensory abnormalities exist and contribute to dysphagia and aspiration is unknown. The purpose of this study was to determine if sensory discrimination in the area innervated by the superior laryngeal nerve diminishes with increasing age. By applying a previously described new device and technique that utilizes brief air pulse stimulation of the anterior wall of the pyriform sinus, sensory discrimination can be reliably determined. We carried out 672 trials in 56 healthy adults divided into three age groups: 20 to 40, 41 to 60, and 61 to 90 years of age. Overall, the average sensory discrimination was 2.30 ± 0.50 mm Hg. In subjects 20 to 40 years of age, sensory discrimination was 2.07 ± 0.20 mm Hg, while in subjects 61 to 90 years of age, sensory discrimination was 2.68 ± 0.63 mm Hg (p < .05). There also was a statistically significant difference between the 41- to 60-year and 61- to 90-year age groups (p < .05). Progressive diminution in pharyngeal and supraglottic sensitivity with increasing age might be a contributing factor in the development of dysphagia and aspiration in the elderly.

FEESST: A New Bedside Endoscopic Test of the Motor and Sensory Components of Swallowing

We here introduce an office or bedside method of evaluating both the motor and sensory components of swallowing, called fiberoptic endoscopic evaluation of swallowing with sensory testing (FEESST). FEESST combines the established endoscopic evaluation of swallowing with a technique that determines laryngopharyngeal (LP) sensory discrimination thresholds by endoscopically delivering air pulse stimuli to the mucosa innervated by the superior laryngeal nerve. Endoscopic assessment of LP sensory capacity followed by endoscopic visualization of deglutition was prospectively performed 148 times on 133 patients with dysphagia over an 8-month period. The patients had a variety of underlying diagnoses, with stroke and chronic neurologic disease predominating (n = 94). Subsequent to LP sensory testing, a complete dysphagia evaluation was conducted. Various food and liquid consistencies were dyed green, and attention was paid to their management throughout the pharyngeal stage of swallowing. Evidence of latent swallow initiation, pharyngeal pooling and/or residue, laryngeal penetration, laryngeal aspiration, and/or reflux was noted. Recommendations for therapeutic intervention were based on information obtained during the FEESST and often involved the employment of compensatory swallowing strategies, modification of the diet or its presentation, placement on non-oral feeding status, and/or referral to other related specialists. All patients successfully completed the examination. In 111 of the evaluations (75%), severe (>6.0 mm Hg air pulse pressure [APP]) unilateral or bilateral LP sensory deficits were found. With puree consistencies, 31% of evaluations with severe deficits, compared to 5% of evaluations with either normal sensitivity or moderate (4.0 to 6.0 mm Hg APP) LP sensory deficits, displayed aspiration (p <.001, χ2 test). With puree consistencies, 69% of evaluations with severe deficits, compared to 24% with normal or moderate deficits, displayed laryngeal penetration (p <.001, χ2 test). FEESST allows the clinician to obtain a comprehensive bedside assessment of swallowing that is performed as the initial swallowing evaluation for the patient with dysphagia.

Clinical Implications of Determining BMPR2 Mutation Status in a Large Cohort of Children and Adults With Pulmonary Arterial Hypertension

BACKGROUND Bone morphogenetic protein receptor type 2 (BMPR2) mutations occur in idiopathic and familial pulmonary arterial hypertension (IPAH, FPAH); however, the impact of these mutations on clinical assessment and disease severity remains unclear. We investigated the role of BMPR2 mutations on acute vasoreactivity and disease severity in IPAH/FPAH children and adults. METHODS BMPR2 mutation types were determined in 147 IPAH/FPAH patients. Hemodynamics were obtained at baseline and with acute vasodilator testing. RESULTS Of 147 patients (69 adults, 78 children; 114 with IPAH, 33 with FPAH), 124 (84%) were BMPR2 mutation-negative, and 23 (16%) were mutation-positive. BMPR2 mutation-positive patients were less likely to respond to acute vasodilator testing than mutation-negative patients (4% vs 33%; p < 0.003; n = 147). BMPR2 mutation-positive children also appeared less likely to respond to acute vasodilator testing than mutation-negative children. BMPR2-positive patients had lower mixed venous saturation (57 +/- 9% vs 62 +/- 10%; p < 0.05) and cardiac index (CI; 2.0 +/- 1.1 vs 2.4 +/- 1.5 liters/min; p < 0.05) than BMPR2-negative patients. CONCLUSIONS Patients with BMPR2 mutations are less likely to respond to acute vasodilator testing than mutation-negative patients and appear to have more severe disease at diagnosis. Determination of BMPR2 mutations appears to help identify IPAH/FPAH children and adults who are unlikely to respond to acute vasodilator testing and, thus, unlikely to benefit from calcium channel blockade (CCB) treatment.

Seronegative celiac disease: increased prevalence with lesser degrees of villous atrophy.

Our aim was to assess differences in the sensitivities of serologic tests used for the diagnosis of celiac disease among patients with varying degrees of villous atrophy. Among 115 adults with biopsy-proven celiac disease who fulfilled strict criteria, including serologic testing at the time of diagnosis and response to a gluten-free diet, 71% had total villous atrophy and 29% partial villous atrophy. Endomysial antibody was positive in 77% of those with total villous atrophy, compared to 33% with partial villous atrophy (P < 0.001). There was no difference in sensitivity when the type of presentation (classical vs. silent) was compared. Endomysial antibody-positive and negative patients did not differ with respect to age at diagnosis, duration of symptoms, mode of presentation, or family history of celiac disease. All anti-tissue transglutaminase-positive patients had TVA on biopsy. Seronegative celiac disease occurs. Endomysial antibody positivity correlates with more severe villous atrophy and not mode of presentation of celiac disease. Serologic tests, in clinical practice, lack the sensitivity reported in the literature.

The Safety of Flexible Endoscopic Evaluation of Swallowing with Sensory Testing (FEESST): An Analysis of 500 Consecutive Evaluations

We assessed the safety of a new office or bedside method of evaluating both the motor and sensory components of swallowing called flexible endoscopic evaluation of swallowing with sensory testing (FEESST). FEESST combines the established endoscopic evaluation of swallowing with a technique that determines laryngopharyngeal sensory discrimination thresholds by endoscopically delivering air-pulse stimuli to the mucosa innervated by the superior laryngeal nerve. Endoscopic assessment of laryngopharyngeal sensory capacity followed by endoscopic visualization of deglutition was prospectively performed 500 times in 253 patients with dysphagia over a 2.5-year period in a tertiary care center. The patients had a variety of underlying diagnoses, with stroke and chronic neurological disease predominating (n= 155). To determine the safety of FEESST, the presence of epistaxis, airway compromise, and significant changes in heart rate before and after the evaluation were assessed. Patients were also asked to rate the level of discomfort of the examination; 498 evaluations were completed. There were three instances of epistaxis that were self-limited. There were no cases of airway compromise. There were no significant differences in heart rate between pre- and posttest measurements (p > 0.05). Eighty-one percent of patients noted either no discomfort or mild discomfort as a result of the examination. In conclusion, FEESST is a safe method of evaluating dysphagia in the tertiary care setting and may also have application for the chronic care setting.

Newborn Hearing Screening in the NICU: Profile of Failed Auditory Brainstem Response/Passed Otoacoustic Emission

Objective. Incidence of a specific pattern of auditory responses, absent auditory brainstem responses (ABRs) and present otoacoustic emissions (OAEs), in newborn hearing screening in a regional perinatal center neonatal intensive care unit (NICU) is described. This profile, labeled auditory neuropathy or auditory dyssynchrony (AN/AD), is a dysfunction in neural/brainstem transmission that occurs in individuals whose outer hairs cells are functioning normally. Although the AN/AD profile has been associated with various risk factors, incidence and prediction are unknown. Method. Analysis of electrophysiologic measures and medical record reviews of the first 22 months of the universal newborn hearing–screening program was conducted. Association of the AN/AD profile was evaluated with the following factors: gender, gestational age, ototoxic drug regimen, low birth weight, hyperbilirubinemia, hydrocephalus, low Apgar score, anoxia, respiratory distress syndrome, pulmonary hypertension, intraventricular hemorrhage, multiple birth, seizure activity, and family history. Results. One hundred fifteen (24.1%) of the 477 infants failed the ABR in 1 or both ears and passed OAEs bilaterally. Comparisons of infants fitting the AN/AD profile with those not fitting the AN/AD profile were negative with 3 exceptions: those with hyperbilirubinemia and those who were administered vancomycin or furosemide. A logistic-regression analysis model failed to predict which infants would be at risk for the AN/AD profile either unilaterally or bilaterally. Conclusions. Screening of NICU infants should be conducted with ABR first, followed by OAE after failure on ABR. Because the incidence of the AN/AD profile was found to be 24% in this at-risk population, additional study is warranted.

Silent laryngopharyngeal sensory deficits after stroke

Dysphagia and aspiration are two devastating sequelae of stroke. Recent work has shown that laryngopharyngeal (LP) sensory deficits are associated with aspiration in stroke patients with dysphagia. The phenomenon of silent LP sensory deficits, where the patient exhibits no subjective or objective evidence of dysphagia, yet has an LP sensory deficit, has not been previously described. The aim of this study was to evaluate the sensory capacity of the laryngopharynx in stroke patients who had no subjective or objective complaints of dysphagia. We determined the sensory threshold in the laryngopharynx using air pulse stimulation of the mucosa of the pyriform sinus and aryepiglottic fold. Eighteen stroke patients (mean age 65.6 ± 11.5 years) and 18 age-matched controls were prospectively evaluated. Normal thresholds were defined as <4.0 mm Hg air pulse pressure (APP). Deficits were defined as either a moderate impairment in sensory discrimination thresholds (4.0 to 6.0 mm Hg APP) or a severe sensory impairment (>6.0 mm Hg APP). Stroke patients were followed up for 1 year to determine the incidence of aspiration pneumonia (AP) as verified by chest radiography. In 11 of the stroke patients studied, either unilateral (n = 6) or bilateral (n = 5) severe sensory deficits were identified. The elevations in sensory discrimination thresholds were significantly greater than those in age-matched controls (7.1 ± 0.6 mm Hg APP versus 2.5 mm Hg APP; p < .01, Wilcoxon score). Among patients with unilateral deficits, sensory thresholds were severely elevated in all cases on the affected side compared with the unaffected side (p < .01, Wilcoxon score). Moreover, the sensory thresholds of the unaffected side were not significantly different from those of age-matched controls. Aspiration pneumonia did not occur in the patients with normal LP sensation or in the patients with unilateral severe LP sensory deficits. However, in the 5 patients with bilateral, severe LP sensory deficits, 2 developed AP, both within 3 months of their LP sensory test. The results of this study showed, for the first time, that stroke patients without subjective or objective clinical evidence of dysphagia could have silent LP sensory deficits. These impairments could contribute to the development of AP following stroke. The findings in this study suggest that LP sensory discrimination threshold testing should not be restricted only to patients with clinical dysphagia.