Search

Sodium channelopathies are among the most common single-gene causes of epilepsy and have been considered model disorders for the study of genetic epilepsies. Epilepsies due to SCN8A pathogenic variants can present with a broad range of phenotypes varying from a severe epileptic encephalopathy with multiple types of drug-resistant seizure to neurodevelopmental delay, mental retardation, and electroencephalogram (EEG) findings of multifocal spike and waves (mostly in the temporal/parietal/occipital areas). In rare cases, benign familial infantile seizures and developmental delay with/without ataxia have been reported. A first-level, specific SCN8A Sanger's sequencing, although available, is rarely performed because the clinical phenotype is not strictly characteristic and several overlaps with other genetic epilepsies may occur. Given its indistinctive phenotype, diagnosis is usually performed through a specific gene panel for epileptic encephalopathies, early epilepsies, or genetic epilepsy in general, or through whole exome sequencing (WES) and more rarely through whole genome sequencing (WGS). Mutations in SCN8A occur as an autosomal dominant trait. The great majority of individuals diagnosed with SCN8A epilepsy do not have an affected parent, because usually SCN8A patients do not reproduce, and mutations are inherited as a “de novo” trait. In rare cases, SCN8A mutations may be inherited in the setting of parental germline mosaicism. SCN8A-related epilepsies have not shown a clear genotype–phenotype correlation, the same variants have been described with different clinical expressivity and this could be due to other genetic factors or to interacting environmental factors. There is no standardized treatment for SCN8A-related epilepsy because of the rarity of the disease and the unavailability of specific, targeted drugs. Treatment is based mainly on antiepileptic drugs which include classic wide-spectrum drugs such as valproic acid, levetiracetam, and lamotrigine. Sodium-channel blockers (phenytoin, carbamazepine, oxcarbazepine, and lamotrigine) have shown appreciable results in terms of seizure reduction, in particular, in patients presenting gain-of-function mutations. Nowadays, new potentially transformative gene therapy treatment approaches are currently being explored, allowing in the next future, a precision-based treatment directed against the gene defect and protein alterations.

In patients with moderate-to-severe Chronic Obstructive Pulmonary Disorder (COPD), pulmonary hyperinflation can occur at rest and increase during episodes of exacerbation. Among other mechanical constraints, changes in position and configuration of the diaphragm are also induced by increased end-expiratory lung volume. Both descent and flattening of diaphragm might damage the phrenic nerves by stretching their fibers. The study aimed to investigate the phrenic nerve conduction in COPD patients in stable conditions and during COPD exacerbation. In a group of 11 COPD patients without relevant comorbidities in stable conditions and subsequently in another group of 10 COPD patients during in-hospital COPD exacerbation and recovery, measurements of functional respiratory parameters and assessment of phrenic nerves motor conduction by bilateral electric stimulation were performed concurrently. Significant increase in phrenic nerves latency (

Bacterial colonization is a well-known phenomenon in acute care, but scant information is available regarding the rehabilitation setting. We retrospectively analyzed, in COPD patients admitted to a Respiratory Rehabilitative unit in 2010, the number of cultures requested, of positive cultures, and of cultures showing multiple drug resistant (MDR) organisms. We also compared hospital admissions (HA) with versus without positive cultures and with versus without MDR and investigated which baseline variables may predict length of stay (LOS)30 days. Of 286 COPD admissions (involving 269 patients, age 71 ± 11 years, males 66%), culture samples were requested in 62 (22%). The rate of colonization and of MDR organisms was 61 and 39%, respectively. Patients with a positive culture had a worse clinical condition and disability, and were more frequently tracheostomized, on invasive mechanical ventilation (MV) and admitted from/discharged to acute care. Patients with MDR cultures showed a lower exercise tolerance. Factors predicting LOS30 days were the presence of comorbidities, invasive MV, age65 years, and lower functional status, but not a positive culture or MDR presence. To our knowledge, this is the first real-life Italian study investigating the epidemiology of colonization and the association between colonization and LOS in a respiratory rehabilitation setting. Further investigation is necessary to clarify the relationship between colonization burden and patients' baseline clinical status and outcomes.

Background Pulmonary rehabilitation (PR) is mandatory before bronchoscopy lung volume reduction (BLVR); there is scant information about its efficacy post-BLVR. We retrospectively evaluated pulmonary function (PF) and disability in patients pre/post-BLVR and its additive effect on an intensive PR program post-BLVR vs matched non-BLVR controls. We analyzed changes within BLVR patients according to presence or not of atelectasis. Methods We compared PF and exercise tolerance (6-min walk test, 6MWT) in 39 BLVR patients (FEV1% pred. 28.9 ± 1.5; RV% pred. 236.1 ± 7.7) pre-/post-BLVR, and vs. 32 controls (FEV1% pred. 32.7 ± 1.5; RV % pred. 217.8 ± 8.3) before and after PR. Results BLVR patients showed a greater improvement than controls in PF (difference between groups: 3.8 for FEV1% pred., p = 0.043; −20.5 for RV % pred., p = 0.02) and 6MWT response rate (12/39 vs. 1/39 subjects, p = 0.003). Both groups further improved significantly 6MWT after PR without a significant difference between groups. Atelectasis after BLVR mainly accounted for the improvement in FEV1% pred, RV% pred. and 6MWT compared to both BLVR without atelectasis and controls. Conclusion BLVR improves PF (particularly RV) and exercise tolerance, patients with lobar exclusion being the best improvers. PR following BLVR yields a further improvement in exercise tolerance in both (atelectasis and non-atelectasis) subgroups.