Rapidly progressive multiple system atrophy in a patient carrying LRRK2 G2019S mutation.

BACKGROUND: Multiple system atrophy (MSA) is considered a primarily sporadic neurodegenerative disease, but the role of genetic is poorly understood. CASE: We present a female patient of Moroccan origin who developed a rapidly progressive non-levodopa responsive parkinsonism, gait and balance problems, and dysautonomia including severe bulbar symptoms. She was diagnosed with MSA Parkinsonian-type (MSA-P) and suddenly died at night at 58 years of age. Reduced striatal DAT-SPECT, putaminal hyperintensity on T2-MRI, and hypometabolism with FDG-PET were present. Genetic testing documented a G2019S mutation in the LRRK2 gene. A skin biopsy was obtained and used to perform alpha-synuclein RT-QuIC, which was negative, and immunohistochemical analysis, which demonstrated abnormal alpha-synuclein deposits in cutaneous nerves. Elevated blood neurofilament light chain levels were also documented. CONCLUSIONS: LRRK2 mutations are the most common cause of monogenic Parkinson's disease (PD) and G2019S is the most frequent variant. Our patient presented with biological, clinical, and radiological features of MSA, but genetic testing revealed a G2019S LRRK2 mutation, which has been previously reported only in one other case of pathologically proven MSA but with mild progression. In our patient, post-mortem confirmation could not be performed, but RT-QuIC and immunohistochemical findings on skin biopsy support the diagnosis of MSA. G2019S LRRK2 may be linked to an increased risk of MSA. Cases of atypical parkinsonism with rapid disease course should be screened for PD-related genes especially in populations with a high prevalence of mutations in known genes.

Deep brain stimulation of globus pallidus internus and subthalamic nucleus in Parkinson's disease: a multicenter, retrospective study of efficacy and safety.

BACKGROUND: Deep brain stimulation (DBS) is an established therapeutic option in advanced Parkinson's disease (PD). Literature data and recent guidelines remain inconclusive about the best choice as a target between the subthalamic nucleus (STN) and the globus pallidus internus (GPi). MATERIALS AND METHODS: We retrospectively reviewed the clinical efficacy outcomes of 48 DBS-implanted patients (33 STN-DBS and 15 GPi-DBS) at a short- (<1 year from the surgery) and long-term (2-5 years) follow-up. Also, clinical safety outcomes, including postoperative surgical complications and severe side effects, were collected. RESULTS: We found no difference between STN-DBS and GPi-DBS in improving motor symptoms at short-term evaluation. However, STN-DBS achieved a more prominent reduction in oral therapy (L-DOPA equivalent daily dose, P = .02). By contrast, GPi-DBS was superior in ameliorating motor fluctuations and dyskinesia (MDS-UPDRS IV, P < .001) as well as motor experiences of daily living (MDS-UPDRS II, P = .03). The greater efficacy of GPi-DBS on motor fluctuations and experiences of daily living was also present at the long-term follow-up. We observed five serious adverse events, including two suicides, all among STN-DBS patients. CONCLUSION: Both STN-DBS and GPi-DBS are effective in improving motor symptoms severity and complications, but GPi-DBS has a greater impact on motor fluctuations and motor experiences of daily living. These results suggest that the two targets should be considered equivalent in motor efficacy, with GPi-DBS as a valuable option in patients with prominent motor complications. The occurrence of suicides in STN-treated patients claims further attention in target selection.

Genetic mutations in Parkinson's disease: screening of a selected population from North-Eastern Italy.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder with a multifactorial pathogenesis. Several genetic variants increase the risk of PD and about 5-10% of cases are monogenic. This study aims to define the genetic bases and clinical features of PD in a cohort of patients from Northeastern Italy, a peculiar geographical area previously not included in genetic screenings. METHODS: Using an NGS multigenic panel, 218 PD patients were tested based on age at onset, family history and development of atypical features. RESULTS: A total of 133 genetic variants were found in 103 patients. Monogenic PD was diagnosed in 43 patients (20% of the cohort); 28 (12.8%) carried mutations in GBA1, 10 in LRRK2 (4.6%) and 5 in PRKN (2.3%). In 17% of patients the genetic defect remained of uncertain interpretation. The selection criterion "age of onset < 55 years" was a significant predictor of a positive genetic test (OR 3.8, p 0.0037). GBA1 patients showed more severe symptoms and a higher burden of motor and non-motor complications compared to negative patients (dyskinesias OR 3, sleep disturbances OR 2.8, cognitive deficits OR 3.6; p < 0.05), with greater autonomic dysfunction (COMPASS-31 score 34.1 vs 20.2, p 0.03). CONCLUSIONS: Applying simple clinical criteria for genetic testing allows to increase the probability to identify patients with monogenic PD and better allocate resources. This process is critical to widen the understanding of disease mechanisms and to increase the individuation of patients potentially benefitting from future disease-modifying therapies.

Expanding endoscopic treatment strategies for pancreatic leaks following pancreato-duodenectomy: a single centre experience.

BACKGROUND AND AIM: Clinically relevant pancreatic leaks of jejunal-pancreatic anastomosis after pancreato-duodenectomy (PD) occur in 9-15% of cases. Endoscopic strategies for management of pancreatic fistula, may allow to avoid reoperation and shorten times for fistula closure, but are still understudied and not widely performed. Aim of the present paper is to describe different endoscopic techniques used to treat such conditions. METHODS: It was a retrospective, single centre, study. All patients who underwent endoscopic treatment for pancreatic leaks following PD between 1st January 2013 and 31th May 2019 at our Centre were reviewed. Depending on the morphology and severity of the leak, four main endoscopic techniques were performed: (1) trans-anastomotic intraductal pancreatic stent insertion; (2) lumen-apposing metal stent between the jejunal loop and the retroperitoneum toward the pancreatic stump insertion ("yoyo-stent"); (3) large calibre nose-to-retroperitoneum drain insertion; (4) when a wide damage of the jejunal wall or a coexistent biliary-jejunal leak were observed, triple metal stent insertion was performed as follow in order to close the defect: enteral fully-covered SEMS in the jejunal stump, a pancreatic metal stent into the Wirsung duct and a fully-covered SEMS across the bilio-digestive anastomosis, through the meshes of the enteral stent. In all cases, surgical drain was simultaneously retracted. RESULTS: We identified 13 patients who underwent endoscopic treatment for POPF after PD. In total, 5 patients underwent "Yoyo stent insertion", 3 with nose-to-collection drain placement and four patients were treated with triple-stent insertion; in only one patient intrapancreatic SEMS insertion was performed. Technical success was 100% and clinical success was 83.3%. Mean time for leak closure was 4.8 days (range 2-10). During the follow-up interval, no leak recurrences were observed. CONCLUSIONS: Our experience confirms efficacy and safety of endoscopic management of POPF following pancreatoduodenectomy management. Endoscopy should play a central role in this clinical scenario.

Endoscopic Findings in Patients Infected With 2019 Novel Coronavirus in Lombardy, Italy.

Coronavirus disease 2019 (COVID-19) is a major worldwide threat caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly spreading to a global pandemic. As of May 11, 2020, 4,176,346 cases have been reported worldwide, 219,814 in Italy, and of them, 81,871 occurred in the Lombardy region.1 Although the respiratory manifestations of COVID-19 have been widely described, the impact on the gastrointestinal (GI) system remains less clear. The reported prevalence of digestive symptoms ranges from 3% to 79%, depending on the setting,2-5 but data on GI endoscopic and histologic findings in COVID-19 patients are lacking. Therefore, the aim of this study is to describe the GI endoscopic and histologic findings in COVID-19 patients.

A Smooth Esophageal Stricture Causing Dysphagia.

Dysphagia in patients with lung cancer is usually due to direct invasion from bronchogenic carcinomas or nodal localizations, while metastases from distant lung neoplasms are considered rare. We report a case of a smooth esophageal narrowing secondary to intramural metastasis from pulmonary adenocarcinoma in a patient with no previous history of neoplasia. Since standard linear echoendoscope could not overpass the malignant stricture, we obtained a histological diagnosis by fine-needle aspiration biopsy using an echobronchoscope (EBUS), due to its lower diameter. The EBUS scope represents a valuable tool to obtain cytological specimens in patients with esophageal strictures.