Paraneoplastic neurological syndrome accompanied by severe central hypoventilation and expression of anti-Hu antibody in a patient with small cell lung cancer]

A 65-year-old man was admitted to our hospital complaining of diplopia, dysarthria, difficulty in walking and progressive dysesthesia that developed in his left hand and leg. Brain MRI revealed high signal intensity regions on T2-weighted and FLAIR images of the hippocampus and the corpus amygdaloideum. After admission, the patient's neurological symptoms progressed to delirium and dementia with hallucinations. When he eventually developed severe respiratory failure requiring ventilatory support, brain MRI revealed new high signal intensity regions on T2-weighted images of the medulla oblongata and pons. Chest CT scans showed a mass under the aortic arch, and based on subsequent histopathological examination of a transesophageal endoscopic ultrasonography-guided fine needle aspiration biopsy of the tumor, a diagnosis of small cell lung cancer was made. In addition, anti-Hu antibody was found in the patient's serum, leading to a diagnosis of paraneoplastic encephalomyelitis/sensory neuropathy. One course of chemotherapy (carboplatin + etoposide) was administered; however, the protocol was not completed because the patient developed severe pneumonia. Given that neurological symptoms usually precede a diagnosis of malignancy in paraneoplastic neurological syndromes, it is important that these are considered carefully, as they may contribute to early diagnosis and treatment. Here we report a rare case of severe central hypoventilation in paraneoplastic encephalomyelitis/sensory neuropathy.     

Mitral regurgitation without supravalvular aortic stenosis in Williams syndrome

Isolated mitral regurgitation without supravalvular aortic stenosis is rarely identified in Williams syndrome. We describe the case of a 24-year-old man with isolated mitral regurgitation in Williams syndrome. Severe regurgitation due to prolapse of the anterior leaflet was noted in an echocardiogram and color Doppler, and a left ventriculogram showed grade IV regurgitation. No pressure gradient between the left ventricle and the ascending aorta was found. Mitral regurgitation had been noted since his birth, and pediatricians suspected Williams syndrome because of postnatal growth deficiency, mental deficiency, unusual personality, and unusual facial features in his childhood. The diagnosis was confirmed by demonstration of the hemizygous deletion of 7q11.23 in the karyotype by the fluorescent in situ hybridization technique after his admission to our department. The patient underwent mitral valve replacement, and microscopic examination of the excised valve revealed myxomatous degeneration. Received: April 10, 2002 / Accepted: June 21, 2002 Acknowledgment Grateful acknowledgment is given to Emeritus Professor Dr. K. Inada, Gifu University, for his review of the pathologic slides. Correspondence to H. Takagi     

G→A mutations in p53 and Ha-ras genes in esophageal papillomas induced by N-nitrosomethylbenzylamine in two strains of rats

In human esophageal cancers, no ras gene mutations but a relatively high prevalence of p53 gene mutations have been reported. We found a high prevalence of point mutations in Ha-ras and p53 genes in N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumors in two strains of rats (BD VI and F344). Our analysis showed the point mutation GGA←GAA (expected from the known mechanisms of action of NMBA) at Ha-ras codon 12 in 22 of 46 (48%) and 22 of 38 (58%) papillomas from BD VI and F344 rats, respectively. There was no significant difference in the prevalence of ras mutations in tumors induced by high doses (5.0 mg/kg) and low doses (2.5 mg/kg) of NMBA. Eleven papillomas from each strain were analyzed for p53 mutations. The prevalent mutations found were G←A and C←T transitions. The frequency of p53 mutation was 36% (four of 11) for each strain. No apparent hot-spot codon or exon was found in the p53 gene, and two papillomas contained double mutations in this gene. The high prevalence of G←A mutations in the rat Ha-ras gene contrasts with that in the human gene, in which no ras mutations have been found in primary tumors, and suggests either that the biology of esophageal carcinogenesis differs in humans and rats or that nitrosamines are not the major etiological risk factor for human esophageal cancers. © 1994 Wiley-Liss, Inc.