Assessment of time intervals in the pathway to oral cancer diagnosis in north-westerm Spain. Relative contribution of patient interval.

BACKGROUND: Despite continuous advances in diagnosis and therapy, oral cancers are mostly diagnosed at advanced stages with minor survival improvements in the last two decades. Both phenomena have been attributed to delays in the diagnosis. This study aims at quantifying the time elapsed until definitive diagnosis in these patients and the patient interval's contribution. MATERIAL AND METHODS: A hospital-based, ambispective, observational study was undertaken on incident cases with a pathological diagnosis of oral squamous cell carcinoma recruited during 2015 at the Oral and Maxillofacial Surgery services of CHUAC (A Coruña) and POVISA (Vigo) hospitals. RESULTS: 74 consecutive oral cancer patients (59.5% males; median age: 65.0 years (IQ:57-74)) were studied. Most cases (52.7%; n=39) were at advanced stages (TNM III-IV) at diagnosis. The period since first sign/symptom until the patient seeks health care was the longest interval in the pathway to diagnosis and treatment (median: 31.5 days; IQR= 7.0 - 61.0) and represents >60% of the interval since symptom onset until referral to specialised care (pre-referral interval). The average interval assigned to the patient resulted to be relatively larger than the time elapsed since the patient is seen at primary care until a definitive diagnosis is reached (diagnostic interval). Median of the referral interval for primary care professionals: 6.5 days (IQR= 0.0 - 49.2) and accounts for 35% (19% - 51%) of the diagnostic interval. CONCLUSIONS: The patient interval is the main component of the pathway to treatment since the detection of a bodily change until the definitive diagnosis. Therefore, strategies focused on risk groups to shorten this interval should be implemented in order to ease an early diagnosis of symptomatic oral cancer.

First mutation in the voltage-gated Nav1.1 subunit gene SCN1A with co-occurring familial hemiplegic migraine and epilepsy.

Almost all mutations in the SCN1A gene, encoding the alpha(1) subunit of neuronal voltage-gated Na(V)1.1 sodium channels, are associated with severe childhood epilepsy. Recently, two mutations were identified in patients with pure familial hemiplegic migraine (FHM). Here, we identified a novel SCN1A L263V mutation in a Portuguese family with partly co-segregating hemiplegic migraine and epilepsy. The L263V mutation segregated in five FHM patients, three of whom also had epileptic attacks, occurring independently from their hemiplegic migraine attacks. L263V is the first SCN1A mutation associated with FHM and co-occurring epilepsy in multiple mutation carriers, and is the clearest molecular link between migraine and epilepsy thus far. The results extend the clinical spectrum associated with SCN1A mutations and further strengthen the molecular evidence that FHM and epilepsy share, at least in part, similar molecular pathways.

Two novel functional mutations in the Na+,K+-ATPase alpha2-subunit ATP1A2 gene in patients with familial hemiplegic migraine and associated neurological phenotypes.

Mutations in the ATP1A2 gene, encoding the alpha2-subunit of the Na+,K+-ATPase, are associated with familial hemiplegic migraine type 2. The majority of ATP1A2 mutations were reported in patients with hemiplegic migraine without any additional neurological findings. Here, we report on two novel ATP1A2 mutations that were identified in two Portuguese probands with hemiplegic migraine and interesting additional clinical features. The proband's of family 1 (with a V362E mutation) had mood alterations, classified as a borderline personality. The proband in family 2 (with a P796S mutation) had mild mental impairment, in addition to hemiplegic migraine; more severe mental retardation was observed in his brother, who also had hemiplegic migraine and carried the same mutation. Cell-survival assays clearly showed abnormal functioning of mutant Na+,K+-ATPase, indicating that both ATP1A2 mutants are disease causing. Additionally, our results suggest a possible causal relationship of the ATP1A2 mutations with the complex clinical phenotypes observed in the probands.