Early spinal muscular atrophy treatment following newborn screening: A 20-month review of the first Italian regional experience.

OBJECTIVES: Mandatory newborn screening (NBS) for spinal muscular atrophy (SMA) was implemented for the first time in Italy at the end of 2021, allowing the identification and treatment of patients at an asymptomatic stage. METHODS: DNA samples extracted from dried blood spot (DBS) from newborns in Apulia region were analysed for SMA screening by using a real-time PCR-based assay. Infants harbouring homozygous deletion of SMN1 exon 7 confirmed by diagnostic molecular tests underwent clinical and neurophysiological assessment and received a timely treatment. RESULTS: Over the first 20 months since regional NBS introduction, four out of 42,492 (0.009%) screened children were found to carry a homozygous deletion in the exon 7 of SMN1 gene, with an annual incidence of 1:10,623. No false negatives were present. Median age at diagnosis was 7 days and median age at treatment was 20.5 days. Three of them had two copies of SMN2 and received gene therapy, while the one with three SMN2 copies was treated with nusinersen. All but one were asymptomatic at birth, showed no clinical signs of disease after a maximum follow-up of 16 months and reached motor milestones appropriate with their age. The minimum interval between diagnosis and the treatment initiation was 9 days. INTERPRETATION: The timely administration of disease-modifying therapies prevented presymptomatic subjects to develop disease symptoms. Mandatory NBS for SMA should be implemented on a national scale.

Viral pathophysiology of multiple sclerosis: A role for Epstein-Barr virus infection?

Multiple sclerosis (MS) is the most common inflammatory demyelinating and degenerative disease of the CNS. The cause of MS is unknown but environmental risk factors are implicated in MS. Several viruses have been proposed as a trigger for MS, and lately Epstein-Barr virus (EBV) has become the leading candidate. An infectious aetiology fits with a number of epidemiological observations in addition to the immunopathological features of the disease. In this review we will summarize the emerging evidence, which demonstrates a strong association between EBV infection and MS. The conundrum remains as to whether EBV is directly involved in the pathophysiology of MS, or alternatively if the immunopathology of MS somehow affects the regulation of EBV infection.

Gene-environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis.

PURPOSE: To determine the role of gene-environmental interactions between the Class I and Class II HLA alleles and the humoral anti-Epstein-Barr Virus (EBV) responses in the development of brain injury and clinical disability in multiple sclerosis (MS) patients. METHODS: A total of 93 MS patients (62 females; 31 males) and 122 healthy controls underwent HLA typing and testing for antibodies against EBV. The MS patients underwent brain MRI and quantitative measurements of T1- and T2-lesion volumes (LVs) and brain parenchymal fraction (BPF) were obtained. There were 54 MS cases that underwent MRI and EBV-antibody assessments at the 3-year follow-up. The anti-EBV panel included measurements of the levels of anti-EBV early antigen (EA) IgG, anti-EBV nuclear antigen (EBNA) IgG and anti-EBV viral capsid antigen (VCA) IgM and anti-EBV VCA IgG. The relationships between HLA alleles, anti-EBV antibody levels, MRI and clinical parameters were assessed in regression analysis. RESULTS: The presence of HLA B7 was associated with increased T1-LV and trends indicating increased anti-EBV VCA IgG levels, higher disability (EDSS) and more destructive MRI parameters (increased T2-LV and decreased BPF). The presence of HLA A2 was associated with lower EDSS and a trend toward decreased anti-EBV VCA IgG levels; the associations with MRI variables were not significant. The HLA B7-A2 haplotype was significantly associated with higher T2-LV and T1-LV and a trend toward lower BPF was observed. CONCLUSIONS: Our data suggest that gene-environment interactions between specific HLA Class I loci and EBV exposure are associated with MRI markers of lesion injury and brain atrophy in MS patients.

Nontraumatic headache in the Emergency Department: a survey in the province of Trieste.

The objective was to study the demographics, diagnostic procedures and therapies employed in order to provide guidelines to Emergency Department (ED) physicians. A six-month retrospective analysis of the records of all patients presenting with nontraumatic headache (NTH) to the EDs of the Province of Trieste was performed. Of 38,238 patients screened, 300 (0.8%) presented with NTH and 49.7% were referred to specialists. Patients were classified as having secondary headache (41.3%), primary headache (24.3%) and headache with no obvious source (NOS) (34.4%). One hundred and seventy patients were treated with mono- or polytherapy. Of 50 patients with migraine, 36 were treated with NSAIDs and 4 with triptans. 68.4% of patients were referred to a general practitioner and 31.6% were admitted. The frequency of NTH was lower than in other studies. NOS headache was frequent. Only 10% of migraineurs received triptans. Diagnostic and therapeutic guidelines for ED physicians are needed.

Regional lobar atrophy predicts memory impairment in multiple sclerosis.

BACKGROUND AND PURPOSE: In recent studies, measures of whole brain atrophy were strongly correlated with neuropsychological testing, explaining more variance than measures of lesion burden in patients with multiple sclerosis. The relationship between regional lobar atrophy and cognitive impairment is yet to be examined. We endeavored to assess the clinical significance of regional lobar atrophy in multiple sclerosis. METHODS: In a cross-sectional study, we evaluated 31 patients with multiple sclerosis with brain MR imaging and neuropsychological testing. Impairment was determined by comparison with demographically matched healthy controls. MR imaging generated measures of lesion burden (fluid-attenuated inversion recovery hyperintense volume), general atrophy (brain parenchymal fraction), central atrophy (lateral ventricle volume), and lobar atrophy (regional brain parenchymal fraction of frontal, temporal, parietal, and occipital lobes in each hemisphere). Neuropsychological testing emphasized measures of processing speed and memory, because these are commonly affected in multiple sclerosis. RESULTS: Patients with multiple sclerosis showed significant atrophy and impairment on all neuropsychological tests. Regional atrophy accounted for the most variance in all regression models predicting memory performance. Left temporal atrophy was the primary predictor of auditory/verbal memory (partial r's = 0.55-0.61), and both left and right temporal atrophy predicted visual/spatial memory performance (partial r's = 0.51-0.67). Models predicting learning consistency retained frontal lobe atrophy measures (partial r's = 0.44-0.68). Central and general atrophy measures were the primary predictors in modeling processing speed (partial r's = 0.42-0.64). CONCLUSION: Regional atrophy accounts for more variance than lesion burden, whole brain atrophy, or lateral ventricle volume in predicting multiple sclerosis-associated memory dysfunction.