Maureen A. Lefton-Greif

Oropharyngeal dysphagia and aspiration in patients with ataxia-telangiectasia

OBJECTIVES To determine whether patients with ataxia-telangiectasia exhibit oropharyngeal dysphagia with concomitant aspiration and to examine the relationships among swallowing function, age, and nutritional status. STUDY DESIGN Seventy patients (mean age, 10.7 years; range, 1.8 to 30 years) had feeding/swallowing and nutritional evaluations. Fifty-one patients, in whom there were concerns about swallowing safety, were examined with a standardized videofluoroscopic swallow study. RESULTS Fourteen of the 51 patients (27%) with histories suggestive of dysphagia demonstrated aspiration. Of these, silent aspiration (aspiration without a cough) occurred in 10 (71%) patients. Aspirators were significantly older than non-aspirators (mean age, 16.9 vs 10.8 years; P =.002). Advancing age was the strongest factor associated with aspiration during continuous drinking (P =.01). In patients with ataxia-telangiectasia, weight and weight/height were abnormally low at all ages and most compromised in older patients. Patients who aspirated had significantly lower mean weight (P <.002) and weight/height z scores (P <.001) than did patients who did not aspirate. CONCLUSIONS Oropharyngeal dysphagia is common and appears to be progressive in patients with ataxia-telangiectasia. Older patients also have a higher incidence of poorer nutritional status. The relationship between dysphagia and nutritional status deserves further investigation.

Quantitative neurologic assessment of ataxia-telangiectasia

Background: Ataxia telangiectasia (A-T) is a rare disorder with many distinctive neurologic features. Although there is substantial individual variation in the rate of progression of these features, their relationship to one another or to age has not been characterized. Methods: We formulated and tested multiple elements that assess different neurologic functions known to be affected by A-T. The overall index was applied to 52 patients with A-T, 2 to 29 years of age. Results: Seven elements items proved to be informative, and three elements were added based on face validity. In a linear regression model of individuals under 19 years of age, controlled for correlation within sibships, age accounted for 87% of the variation in the A-T Index. Conclusion: Despite substantial individual variability of the phenotypic elements of A-T, scores on this multidimensional index have a very high correlation with age, indicating that there is a characteristic rate of progression of the disease, although functional domains in the brain are differentially affected. The pattern of scores suggests that a severe and a mild form of A-T may be distinguished by this quantitative measure. With further development this index may become useful as an outcome measure for treatment studies and prognosis.

Evaluation and management of pulmonary disease in ataxia‐telangiectasia

Ataxia‐telangiectasia (A‐T) is a rare autosomal recessive disorder caused by mutations in the ATM gene, resulting in faulty repair of breakages in double‐stranded DNA. The clinical phenotype is complex and is characterized by neurologic abnormalities, immunodeficiencies, susceptibility to malignancies, recurrent sinopulmonary infections, and cutaneous abnormalities. Lung disease is common in patients with A‐T and often progresses with age and neurological decline. Diseases of the respiratory system cause significant morbidity and are a frequent cause of death in the A‐T population. Lung disease in this population is thought to exhibit features of one or more of the following phenotypes: recurrent sinopulmonary infections with bronchiectasis, interstitial lung disease, and lung disease associated with neurological abnormalities. Here, we review available evidence and present expert opinion on the diagnosis, evaluation, and management of lung disease in A‐T, as discussed in a recent multidisciplinary workshop. Although more data are emerging on this unique population, many recommendations are made based on similarities to other more well‐studied diseases. Gaps in current knowledge and areas for future research in the field of pulmonary disease in A‐T are also outlined. Pediatr. Pulmonol. 2010; 45:847–859.

Ataxia telangiectasia: a review

Definition of the diseaseAtaxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome.EpidemiologyThe world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births.Clinical descriptionA-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages. Neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities including immunoglobulin and antibody deficiencies and lymphopenia. People with A-T have an increased predisposition for cancers, particularly of lymphoid origin. Pulmonary disease and problems with feeding, swallowing and nutrition are common, and there also may be dermatological and endocrine manifestations.EtiologyA-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated) gene which encodes a protein of the same name. The primary role of the ATM protein is coordination of cellular signaling pathways in response to DNA double strand breaks, oxidative stress and other genotoxic stress.DiagnosisThe diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with one or more of the following which may vary in their appearance: telangiectasia, frequent sinopulmonary infections and specific laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T lymphocytes and increased alpha-fetoprotein levels). Because certain neurological features may arise later, a diagnosis of A-T should be carefully considered for any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be confirmed by the finding of an absence or deficiency of the ATM protein or its kinase activity in cultured cell lines, and/or identification of the pathological mutations in the ATM gene.Differential diagnosisThere are several other neurologic and rare disorders that physicians must consider when diagnosing A-T and that can be confused with A-T. Differentiation of these various disorders is often possible with clinical features and selected laboratory tests, including gene sequencing.Antenatal diagnosisAntenatal diagnosis can be performed if the pathological ATM mutations in that family have been identified in an affected child. In the absence of identifying mutations, antenatal diagnosis can be made by haplotype analysis if an unambiguous diagnosis of the affected child has been made through clinical and laboratory findings and/or ATM protein analysis.Genetic counselingGenetic counseling can help family members of a patient with A-T understand when genetic testing for A-T is feasible, and how the test results should be interpreted.Management and prognosisTreatment of the neurologic problems associated with A-T is symptomatic and supportive, as there are no treatments known to slow or stop the neurodegeneration. However, other manifestations of A-T, e.g. immunodeficiency, pulmonary disease, failure to thrive and diabetes can be treated effectively.

Elevated Serum IL-8 Levels in Ataxia Telangiectasia

Serum interleukin (IL)-8 levels were measured in 50 patients with ataxia telangiectasia (A-T) and 22 without A-T. In a cross-sectional study, the geometric mean of IL-8 level was significantly higher in the patients with A-T (P <.0001). Elevated serum IL-8 levels in patients with A-T suggest that systemic inflammation may contribute to the disease phenotype.

Interdisciplinary Pediatric Aerodigestive Care and Reduction in Health Care Costs and Burden

IMPORTANCE Children with complex respiratory and gastrointestinal disorders frequently require care from multiple pediatric subspecialists. Interdisciplinary pediatric aerodigestive clinic centers have been established at several pediatric tertiary care centers in the United States. Their effectiveness is unknown. OBJECTIVE To determine whether an interdisciplinary approach to pediatric aerodigestive disorders reduces health care costs and burden. DESIGN, SETTING, AND PARTICIPANTS Retrospective medical record review for the first 125 unique pediatric patients (median age, 1.51 years) seen at the Pediatric Aerodigestive Center (PAC) for aerodigestive disorders between June 2010 and August 2013 for a total of 163 outpatient clinical encounters. The PAC is an academic pediatric tertiary care center where specialists in gastroenterology, otolaryngology, pulmonology, and speech-language pathology provide interdisciplinary evaluation during a single clinic encounter and combined operative management when indicated. INTERVENTIONS Interdisciplinary evaluation and treatment of pediatric aerodigestive disorders. MAIN OUTCOMES AND MEASURES Number of operative procedures and estimated hospital charges related to combining clinic encounters and operative procedures. RESULTS During the initial visit, each of the 125 patients received a mean (SD) of 2.9 (0.8) of a potential 4 services. Estimating per-encounter visit costs for gas, parking, and facility fees, we found that the average cost savings per family per PAC visit was

Oropharyngeal dysphagia assessment and treatment efficacy: setting the record straight (response to Campbell-Taylor)

182. Evaluation under anesthesia was recommended for 85 patients (68%), resulting in 267 operative procedures performed by participating services during 158 encounters with general anesthesia. Thus, 109 episodes of anesthesia were avoided (41% reduction), reducing the risks of anesthesia and related care costs (

Safety and caregiver satisfaction with gastrostomy in patients with Ataxia Telangiectasia

1985 per avoided episode). CONCLUSIONS AND RELEVANCE Coordination of interdisciplinary care in the PAC resulted in a reduction of hospital charges realized through reduction in clinic- and anesthesia-related visits. Reductions in episodes of anesthesia may also reduce neurocognitive risks associated with multiple anesthetic exposures. Other nontangible benefits associated with the coordination of care, such as caregiver satisfaction, warrant further study.

Pulmonary function in children and young adults with ataxia telangiectasia.

In September 2008, an article was published in the Journal of the American Medical Directors Association criticizing current dysphagia assessment and management practices performed by speech-language pathologists in Long-Term Care (LTC) settings. In the same issue, an editorial invited dialogue on the points raised by Campbell-Taylor. We are responding to this call for dialogue. We find Campbell-Taylors interpretation of the literature to be incomplete and one-sided, leading to misleading and pessimistic conclusions. We offer a complementary perspective to balance this discussion on the 4 specific questions raised: (1) Is the use of videofluoroscopy warranted for evaluating dysphagia in the LTC population? (2) How effective are thickened liquids and other interventions for preventing aspiration and do they contribute to reduction of morbidity? (3) Can aspiration be prevented and is its prevention important? and (4) Is there sufficient evidence to justify dysphagia intervention by speech language pathologists?

Day Care Increases the Risk of Respiratory Morbidity in Chronic Lung Disease of Prematurity

BackgroundAtaxia Telangiectasia (A-T) is a rare monogenetic neurodegenerative disease with pulmonary, nutritional, and dysphagic complications. Gastrostomy tube (GT) feedings are commonly recommended to manage these co-morbidities. In general, outcomes of GT placement in patients with progressive diseases that develop during childhood are not well characterized. The primary purposes of this study were to determine whether GT placement in patients with A-T would be tolerated and associated with caregiver satisfaction.MethodsWe completed a retrospective review of 175 patients who visited the A-T Childrens Center at Johns Hopkins Hospital from 2001 through 2008, and identified 28 patients with A-T (19 males, 9 females) who underwent GT placement for non-palliative reasons. Information was obtained from medical records, interviews with primary health care providers, and 24 (83%) caregivers of patients with GTs who responded to survey requests.ResultsTwenty-five (89%) patients tolerated GT placement and were a median of 5.0 (0.4-12.6) years post GT placement at the time of this investigation. Three (11%) patients died within one month of GT placement. In comparison to patients who tolerated GT placement, patients with early mortality were older when GTs were placed (median 24.9 vs. 12.3 years, p = 0.006) and had developed a combination of dysphagia, nutritional, and respiratory problems. Caregivers of patients tolerating GT placement reported significant improvements in mealtime satisfaction and participation in daily activities.ConclusionsGT placement can be well tolerated and associated with easier mealtimes in patients with A-T when feeding tubes are placed at young ages. Patients with childhood onset of disorders with predictable progression of the disease process and impaired swallowing may benefit from early versus late placement of feeding tubes.