Ataxia with vitamin E deficiency in the Philippines†: A case report of two siblings.

Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021.

Cough triggers and their pathophysiology in patients with prolonged or chronic cough.

BACKGROUND: The character or timing of chronic cough is considered to be unpredictable for diagnosing its cause. However, the associations of cough triggers with cough pathophysiology remains unknown. METHODS: We developed a closed questionnaire listing 18 triggers that were reported by ≥1% of 213 patients in a retrospective survey. Using this questionnaire, patients with cough-predominant or cough-variant asthma (n = 140) and those with non-asthmatic cough (54) were asked whether their cough was induced by the listed triggers. Associations of triggers with causes of cough, airway sensitivity to inhaled methacholine, exhaled nitric oxide (NO) levels, number of sensitizing allergens, and scores from gastroesophageal reflux (GER) questionnaires were examined. Factor analysis was used to categorize variables, including the 12 most common cough triggers, diagnosis of asthmatic cough, airway sensitivity, and exhaled NO levels. RESULTS: "Cold air" and "fatigue/stress" induced cough more often in asthmatic coughers than in non-asthmatic coughers. "Spices" and "meals" induced cough more frequently in GER-coughers (n = 19). Patients who marked "cold air" as the trigger were more sensitive to inhaled methacholine and showed higher exhaled NO levels than those who did not mark this trigger. The "post-nasal drip" trigger was associated with elevated exhaled NO levels, and this association was mainly exhibited by patients with cough-predominant asthma. The triggers "pollen" and "mold smell" were associated with a number of sensitizing allergens. The number of triggers was weakly associated with GER scores. By factor analysis, "cold air," "fatigue/stress," asthmatic cough, airway hypersensitivity, and elevated NO levels were categorized into the same factor. CONCLUSIONS: Several cough triggers may reflect the pathophysiology of prolonged or chronic cough.

An unusual iatrogenic foreign body (surgical gauze) in the trachea.

We report the case of a 60-year-old male with history of surgery for tracheal stenosis 21 years prior to the onset of difficult asthma-like symptoms. Upon exploring the tracheobronchial tree using the fiberoptic bronchoscope, a surgical gauze was found. The foreign body migrated transluminally from the mediastinum into the trachea and its removal was possible with rigid bronchoscopy leading to a rapid recovery of his symptoms.

Airway wall thickening in patients with cough variant asthma and nonasthmatic chronic cough.

BACKGROUND: Chronic cough, which may be of asthmatic or nonasthmatic origin, is an important clinical issue. Airway inflammation, and remodeling demonstrated by subbasement membrane thickening has been associated with cough variant asthma (CVA) as well as with nonasthmatic chronic cough (NAC). CT studies have shown airway wall thickening in patients with asthma who wheeze. We examined airway wall thickness by CT in adult patients with chronic cough and examined its pathophysiologic implication. METHODS: Nonsmoking, steroid-naïve patients with CVA (n = 27), NAC (n = 26), and healthy control subjects (n = 15) were studied. Airway dimensions were assessed by a validated CT technique, in which we measured airway wall area (WA) corrected by body surface area (BSA), the ratio of WA to outer wall area (percentage of wall area [WA%]), absolute wall thickness (T)/ square root BSA, and airway luminal area/BSA of a segmental bronchus. Correlations between CT parameters and clinical indexes such as disease duration and cough sensitivity were examined. RESULTS: In patients with CVA, WA/BSA, WA%, and T/ square root BSA were all significantly greater than those in control subjects. In patients with NAC, WA/BSA and T/ square root BSA were significantly greater than in control subjects. The increase of WA/BSA and T/ square root BSA of NAC patients was less than that of CVA patients. In a subset of patients with NAC, WA% correlated with capsaicin cough sensitivity (n = 9, r = 0.75, p = 0.034). CONCLUSIONS: Walls of central airways are thickened in patients with CVA, and also to a lesser degree in patients with NAC. Airway wall thickening in NAC may be associated with cough hypersensitivity.

Cell profiles of bronchoalveolar lavage fluid as prognosticators of idiopathic pulmonary fibrosis/usual interstitial pneumonia among Japanese Patients.

BACKGROUND: The role of bronchoalveolar lavage fluid (BALF) cell profiles in predicting the clinical outcome of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is still under discussion. OBJECTIVE: To determine whether BALF cell profiles affect the survival of patients with UIP diagnosed by surgical lung biopsy/autopsy at the early stage of IPF. METHODS: This hospital-based retrospective cohort study used 81 Japanese patients with histologically proven IPF/UIP who underwent BAL examination. The BALF samples were obtained from non-current smokers: NCS (n = 41) and current smokers: CS (n = 40). The Kaplan-Meier and Cox's proportional hazard methods were used to estimate the survival and evaluate the risk ratio for death in the two groups. To detect the multicollinearity, a stepwise regression was employed. RESULTS: A slight increase in the absolute numbers of BALF neutrophils tended to relate to a decrease in the relative risk for death in NCS patients and CS patients in the univariate analysis. In stepwise regression, the increase in percent vital capacity and the increase in the BALF CD4/CD8 ratio in NCS was detected as a favorable predictor, while increased BALF cells affected the results due to chronic smoking in CS. CONCLUSIONS: Based on the study bias of the biopsy-proven IPF/UIP patients at stable stages, an independent variable indicating a favorable outcome was an increased BALF CD4/CD8 ratio in NCS patients, while it was difficult to identify definite prognosticators in CS patients.

Patient characteristics and clinical features of Japanese sarcoidosis patients with low bronchoalveolar lavage CD4/CD8 ratios.

BACKGROUND: Previous studies have shown that there is an association between low BALF (bronchoalveolar lavage fluid) CD4/CD8 ratio and lower remission rates in sarcoidosis patients. AIM: To investigate the patient characteristics and clinical features of Japanese sarcoidosis patients with low BALF CD4/CD8 ratios. METHODS: 322 Japanese sarcoidosis patients were retrospectively analyzed, and 3 groups were selected according to BALF CD4/CD8 ratios as follows: patients with the BALF CD4/CD8 ratio in the lowest 5 percentile (Group 1: 0.43-1.41), median 5 percentile (Group II: 4.68-5.47), and top 5 percentile (Group III: 12.6-60.1). Each group consisted of 16 patients (5% of 322 patients). The patient characteristics, clinical features, and the short-term prognosis for at least 2 years (average 116 months) were compared among the groups. Multivariate analysis was performed for 322 patients to investigate the determinants of BALF CD4/CD8 ratios. RESULTS: The number of BALF CD8+ cells were greater in Group I than in the other two groups. In Group I, there were higher incidences of younger age, male gender, and lower number of extrathoracic lesions compared with Group III. Multivariate analysis showed that younger age and male gender were independently associated with low BALF CD4/CD8 ratios. The frequency of treatment with corticosteroid and progression to pulmonary fibrosis tended to be higher in Group I. CONCLUSIONS: Low BALF CD4/CD8 ratios were due to increased number of BALF CD8+ cells. Younger age and male gender were independently associated with low BALF CD4/CD8 ratios in sarcoidosis patients.

Diabetes insipidus from neurosarcoidosis: long-term follow-up for more than eight years.

Four patients with sarcoidosis presented as hypothalamic-hypophyseal syndrome including diabetes insipidus (DI) were followed up for more than 8 years from the onset of clinical manifestation. The mean age was 26 years, male : female ratio was 3 : 1 and the mean disease duration of 10 years. All patients had hypogonadism, hyperprolactinemia. Pituitary enlargement with thickening of the pituitary stalk were detected by magnetic resonance imaging (MRI) with gadolinium enhancement and attenuation in the intensity of the posterior lobe of the pituitary was detected without enhancement. Corticosteroid therapy resulted in the initial improvement of symptoms and gradual decrease in the tumor size but failed to cure polyuria due to DI. The use of desmopressin was necessary for a long period. None of these patients died from DI or central neurosarcoidosis.