Hypocretin/orexin and narcolepsy: new basic and clinical insights.

Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain-Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for 'narcolepsy with cataplexy' and 'narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress.

Usefulness of intra-oral ultrasonography to predict neck metastasis in patients with tongue carcinoma.

OBJECTIVE: To assess tissue characterization relating with neck metastasis of invasive tongue cancer, we investigate the usefulness of intra-oral ultrasonography (US). MATERIALS AND METHODS: The patients with squamous cell carcinoma of the tongue (n = 110) were preoperatively evaluated with intra-oral US. The US images were compared with histological sections. The histological and ultrasonographic parameters were evaluated for their correlation with neck metastasis. RESULTS AND CONCLUSION: High-quality ultrasonic images were obtained, and all lesions over 1 mm thickness by histology were detected. There was a significant correlation (P < 0.0001) between measurements of tumor thickness by US and histology. Univariate analysis showed that the histological parameters influencing neck metastasis were mode of invasion (P = 0.0006), muscular invasion (P < 0.0001), stromal reaction (P = 0.0002), and tumor thickness (P = 0.0004). Of the ultrasonographic parameters, shape of margin (P = 0.019), pattern of margin (P = 0.033), internal echo signal (P = 0.035), and tumor thickness (P < 0.0001) showed a significant correlation with neck metastasis. Ultrasound images of oral tongue cancer reflected the histological structures. Tumors with diffuse invasive mode shows an irregular and unclear tumor margins on US image. Thickness of 8 mm by ultrasound is useful as a cut-off point of predicting risk of neck metastasis of tongue cancer. Intra-oral US is a reliable tool in objectively predicting subclinical neck metastasis in tongue cancer.

Lateral cephalometric analysis of the pharyngeal airway space affected by head posture.

To clarify the relationship between head posture and pharyngeal airway space (PAS), the cephalometric parameters at different head postures were examined. Twelve normal Japanese adults (6 males and 6 females) were examined. Lateral cephalometric radiographs were taken at five different head postures in each person. All radiographs were traced, and the measurements were analyzed statistically. PAS was significantly increased by forward inclination of the cervical spine. The most significant correlation was found between the change in CVT/NSL (cranio-cervical inclination in the second and fourth vertebrae) and the change in PAS-TP (the minimal pharyngeal airway space) (r(2)=0.79 in males, r(2)=0.67 in females). The mean CVT/NSL when the head was in the natural (neutral) position was 100.9 degrees in males and 103.5 degrees in females. Linear regression analysis revealed DeltaPAS (mm)=0.37DeltaCVT/NSL (degree) (r(2)=0.79, p<0.0001) in males, and DeltaPAS (mm)=0.33DeltaCVT/NSL (degree) (r(2)=0.51, p<0.0001) in females. The correlation equations were obtained as follows: the corrected PAS (mm)=the actual PAS (mm)+0.37[100.9-the actual NSL/CVT (degree)] in males, and the corrected PAS (mm)=the actual PAS (mm)+0.33[103.5-the actual NSL/CVT (degree)] in females. These results will contribute to obtaining an accurate assessment of the PAS that should be corrected by the cranio-cervical inclination.