Clinical variability and female penetrance in X-linked familial FTD/ALS caused by a P506S mutation in UBQLN2.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease leading to progressive paralysis that is generally fatal. Only 10% of cases are familial, a subset of which overlaps with frontotemporal dementia (FTD). Up to half of ALS patients have cognitive impairment, with 15% meeting the criteria for FTD. Clinical sequencing of UBQLN2 in a family with X-linked FTD/ALS with suspected incomplete penetrance, manifesting in both genders, revealed a P506S mutation in. Affected individuals were diagnosed with various conditions including hereditary spastic paraplegia (HSP), bulbar palsy and multiple sclerosis. The mutation in UBQLN2 was first identified in a 35-year-old female who presented with one year of progressive dysarthria, dyspnea, dysphagia, and cognitive decline. EMG suggested early motor neuron disease with prominent bulbar involvement. Her cognition declined rapidly and she developed extremity weakness. Her brother, initially diagnosed with HSP, and her second cousin, with primary lateral sclerosis, also have a P506S mutation in UBQLN2. In conclusion, the P506S mutation in UBQLN2 can affect both males and females and displays great phenotypic variability within the same family. Females can potentially have a more severe and rapidly progressive presentation than their male relatives. Additionally, the P506S mutation can also cause an FTD phenotype.

Posterior lingual lidocaine: a novel method to improve tolerance in upper gastrointestinal endoscopy.

AIM: To evaluate the effect of posterior lingual lidocaine swab on patient tolerance to esophagogastroduodenoscopy, the ease of performance of the procedure, and to determine if such use will reduce the need for intravenous sedation. METHODS: Eighty patients undergoing diagnostic esophagogastroduodenoscopy in a tertiary care medical center were randomized to either lidocaine swab or spray. Intravenous meperidine and midazolam were given as needed during the procedure. RESULTS: Patients in the lidocaine swab group (SWG) tolerated the procedure better than those in the spray group (SPG) with a median tolerability score of 2 (1, 4) compared to 4 (2, 5) (P < 0.01). The endoscopists encountered less difficulty performing the procedures in the SWG with lower median difficulty scores of 1 (1, 5) compared to 4 (1, 5) in the SPG (P < 0.01). In addition, the need for intravenous sedation was also lower in the SWG compared to the SPG with fewer patients requiring intravenous sedation (13/40 patients vs 38/40 patients, respectively, P < 0.01). The patients in the SWG were more satisfied with the mode of local anesthesia they received as compared to the SPG. In addition, the endoscopists were happier with the use of lidocaine swab. CONCLUSION: The use of a posterior lingual lidocaine swab in esophagogastroduodenoscopy improves patient comfort and tolerance and endoscopist satisfaction and decreases the need for intravenous sedation.