Geographic differences in the incidence of Huntington's disease in Sardinia, Italy.

BACKGROUND: The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non-Asian populations. We have recently examined the prevalence of HD in the southern part of Sardinia, a large Italian Mediterranean island that is considered a genetic isolate. We observed regional microgeographic differences in the prevalence of HD across the study area similar to those recently reported in other studies conducted in European countries. To explore the basis for this variability, we undertook a study of the incidence of HD in Sardinia over a 10-year period, 2009 to 2018. METHODS: Our research was conducted in the 5 administrative areas of Sardinia island. Case patients were ascertained through multiple sources in Sardinia and Italy. RESULTS: During the incidence period 53 individuals were diagnosed with clinically manifested HD. The average annual incidence rate 2009-2018 was 2.92 per 106 persons-year (95% CI, 2.2 to 3.9). The highest incidence rate was observed in South Sardinia (6.3; 95% CI, 4.2-9.5). This rate was significantly higher (p<0.01) than the rates from Cagliari, Oristano, and Sassari provinces but did not significantly differ (p = 0.38) from the Nuoro rate. CONCLUSIONS: The overall incidence of HD in Sardinia is close to the correspondent estimates in Mediterranean countries. Our findings highlight also the possibility of local microgeographic variations in the epidemiology of HD that might reflect several factors, including a possible founder effect in the rural areas of South Sardinia and Nuoro.

Prevalence of Huntington's disease in Southern Sardinia, Italy.

BACKGROUND: The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non Asian populations. In Italy, two recent studies performed in Ferrara county and Molise provided different prevalence estimates, varying from 4.2 × 105 to 10.8 × 105. Here we present a study performed in the Southern part of Sardinia, a large Italian mediterranean island that is considered a genetic isolate. METHODS: The study area included the two neighbouring counties of South Sardinia and Cagliari with 353,830 and 431,955 inhabitants respectively on December 31st, 2017 (prevalence date). Case-patients were ascertained through multiple sources in Sardinia and Italy. RESULTS: We identified 54 individuals with HD, of whom 47 were alive on prevalence date. The resulting prevalence rate was 5.98 × 105 in the overall study area, however with marked variations between South Sardinia and Cagliari (9.6 × 105 vs. 3.0 × 105, p = 0.02). In the two study areas, we found similar CAG repeat length in normal alleles (17.5 ± 2.1 vs. 17.7 ± 2.2, p = 0.5). CONCLUSIONS: The overall prevalence of HD in Sardinia is close to the correspondent estimates in Europeans. Our findings also highlighted the possibility of local microgeographic variations in the epidemiology of HD.

Restless legs syndrome in multiple sclerosis: a case-control study.

The aim of our study was to explore restless legs syndrome (RLS) frequency in multiple sclerosis (MS)-patients and establish whether RLS could be a symptom of MS. Over a period of 1 year, we consecutively enrolled 202 MS-patients and 212 healthy controls, matched for sex and age, in a case-control study. All of them filled in a structured questionnaire according to IRLSSG criteria. Those patients who fit the diagnostic criteria were subsequently examined by a neurologist to verify the effective presence of RLS. A total of 91 MS-patients (45%) responded positively to the questionnaires. The diagnosis of RLS was carried out in 29 subjects (14.4%). Among the healthy controls, a definite diagnosis of RLS was achieved only in 6 subjects (2.8%). The risk of MS patients to present RLS was significantly higher (OR.5.76 P:0.00002) than the general population. None of them was affected by other medical conditions related to RLS developing. The 62 remaining patients presented numbness and weakness of the legs not suggestive of RLS. Our findings confirm a significant correlation between MS and RLS. In our opinion, MS must be definitively included among RLS causes.

LRRK2 mutations and Parkinson's disease in Sardinia--A Mediterranean genetic isolate.

The Leucine-Rich Repeat Kinase 2 (LRRK2) Gly2019Ser mutation is frequent among Parkinson's disease (PD) patients from the Arab, Jewish, and Iberian populations, while another mutation, Arg1441Gly, is common in the Basque population. We studied the prevalence of these mutations in Sardinia, a Mediterranean genetic isolate with peculiar structure and similarities with the Basque population. Among 98 Sardinian PD probands we detected one heterozygous Gly2019Ser carrier. This mutation was also found in one of 55 Sardinian controls, an 85-year-old man, later shown to have a positive family history of parkinsonism. No carriers of Arg1441Gly, Arg1441Cys, or Arg1441His mutations were found among cases and controls. Our results suggest that the "Basque"LRRK2 mutation is absent or very rare in Sardinia. The Gly2019Ser mutation is present but its frequency is lower than that in Iberian, Arab, or Jewish populations. The identification of an 85-year-old, healthy Gly2019Ser carrier supports the concept that this mutation displays incomplete penetrance.

Effect of dose and frequency of interferon beta-1a administration on clinical and magnetic resonance imaging parameters in relapsing-remitting multiple sclerosis.

There is still debate over the optimal dosage, frequency and route of administration of interferon (IFN) beta in multiple sclerosis (MS). A prospective, non-randomized, comparative study was performed to evaluate differences in magnetic resonance imaging and clinical outcomes of two IFN beta-1a preparations (30mcg intramuscular [im] once-weekly [qw], AVO; and 22 mcg subcutaneous [sc] three-times-weekly [tiw]; R22). Relapsing-remitting MS patients on one of the two IFN preparations (AVO, n=47; R22, n=48) were assessed at baseline and after 6 months of further treatment. There were no significant differences between the two groups at baseline. Both groups showed significantly reduced relapse rates (F=19.5; p<0.001) from baseline (0.6) to 6-month assessment (0.2; p<0.001). Univariate analysis showed a significant difference in favour of R22 on T2 lesion volume (F=14.4; p<0.001) and T1 black hole lesion load (F=8.5; p=0.004), the latter showing a significant increase in the AVO group (p<0.001). The incidence of patients with new T1 black holes was also higher for AVO than R22 (23.5% vs 8.3%; p=0.025). These results from patients receiving AVO or R22 in normal clinical practice are in line with randomized clinical studies that show the benefits of high-dose, high-frequency administration of IFN beta-1a in MS therapy.

Prevalence of primary blepharospasm in Sardinia, Italy: a service-based survey.

We performed a service-based epidemiological study of primary blepharospasm in the island of Sardinia (Italy). Due to its favorable geographical location, we are confident we will provide reliable data from patients seeking botulinum toxin treatment. A total of 53 patients were assessed. Prevalence was estimated to be 32.2 per 1 million (95% confidence interval, 23.0-40.8). These results are in line with those obtained in other similar surveys, that is, record-based, and performed in various European regions such as Northern England, the Munich area, as well as the Epidemiologic Study of Dystonia in Europe.