No abstract

Recent studies identified rare missense mutations in amyotrophic lateral sclerosis (ALS) patients in the TARDBP gene encoding TAR DNA binding protein (TDP)-43, the major protein of the ubiquitinated inclusions (UBIs) found in affected motor neurons (MNs). The aim of this study was to further define the spectrum of TARDBP mutations in a large cohort of 666 Italian ALS patients (125 familial and 541 sporadic cases). The entire coding region was sequenced in 281 patients, while in the remaining 385 cases only exon 6 was sequenced. In 18 patients, of which six are familial, we identified 12 different heterozygous missense mutations (nine novel) all locating to exon 6, which were absent in 771 matched controls. The c.1144G>A (p.A382T) variation was observed in seven patients, thus representing the most frequent TARDBP mutation in ALS. Analysis of microsatellites surrounding the TARDBP gene indicated that p.A382T was inherited from a common ancestor in 5 of the 7 patients. Altogether, the frequency of TARDBP gene mutations appears to be particularly high in Italian ALS patients compared to individuals of mainly Northern European origin (2.7% vs. 1%). Western blot analysis of lymphocyte extracts from two patients carrying the p.A382T and p.S393L TARDBP mutations showed the presence of lower molecular weight TDP-43 bands, which were more abundant than observed in healthy controls and patients negative for TARDBP mutations. In conclusion, this report contributes to the demonstration of the causative role of the TARDBP gene in ALS pathogenesis and indicates that mutations may affect the stability of the protein even in nonneuronal tissues.

No abstract

Our results demonstrate that direct injection of autologous expanded MSCs into the spinal cord of ALS patients is safe, with no significant acute or late toxicity, and well tolerated. The clinical results seem to be encouraging.

The aim of this study was to asses the clinical features, pattern of healthcare and drug utilization of migraine patients attending 10 Italian headache centres (HC). Migraine is underdiagnosed and undertreated everywhere throughout the world, despite its considerable burden. Migraine sufferers often deal with their problem alone using self-prescribing drugs, whereas triptans are used by a small proportion of patients. All patients attending for the first time 10 Italian HCs over a 3-month period were screened for migraine. Migraine patients underwent a structured direct interview about previous migraine diagnosis, comorbidity, headache treatments and their side-effects and healthcare utilization for migraine. Patient satisfaction with their usual therapy for the migraine attack was evaluated with the Migraine-Assessment of Current Therapy (ACT) questionnaire. The quality of life of migraine patients was assessed by mean of Short Form (SF)-12 and Migraine-Specific Quality of life (MSQ) version 2.1 questionnaires. Of the 2675 patients who attended HCs for the first time during the study period, 71% received a diagnosis of migraine and the first 953 subjects completed the study out of 1025 patients enrolled. Only 26.8% of migraine patients had a previous diagnosis of migraine; 62.4% of them visited their general practitioner (GP) in the last year, 38.2% saw a specialist for headache, 23% attended an Emergency Department and 4.5% were admitted to hospital for migraine; 82.8% of patients used non-specific drugs for migraine attacks, whereas 17.2% used triptans and only 4.8% used a preventive migraine medication. Triptans were used by 46.4% of patients with a previous diagnosis of migraine. About 80% of migraine patients took over-the-counter medications. The Migraine-ACT revealed that 60% of patients needed a change in their treatment of migraine attacks, 85% of whom took non-specific drugs. Both the MSQ version 2.1 and the SF-12 questionnaires indicated a poor quality of life of most patients. Migraine represents the prevalent headache diagnosis in Italian HCs. Migraine is still underdiagnosed in Italy and migraine patients receive a suboptimal medical approach in our country, despite the healthcare utilization of migraine subjects being noteworthy. A cooperative network involving GPs, neurologists and headache specialists is strongly desirable in order to improve long-term migraine management in Italy.