High-Throughput Sequencing Haplotype Analysis Indicates in LRRK2 Gene a Potential Risk Factor for Endemic Parkinsonism in Southeastern Moravia, Czech Republic

Parkinson’s disease and parkinsonism are relatively common neurodegenerative disorders. This study aimed to assess potential genetic risk factors of haplotypes in genes associated with parkinsonism in a population in which endemic parkinsonism and atypical parkinsonism have recently been found. The genes ADH1C, EIF4G1, FBXO7, GBA, GIGYF2, HTRA2, LRRK2, MAPT, PARK2, PARK7, PINK1 PLA2G6, SNCA, UCHL1, and VPS35 were analyzed in 62 patients (P) and 69 age-matched controls from the researched area (C1). Variants were acquired by high-throughput sequencing using Ion Torrent workflow. As another set of controls, the whole genome sequencing data from 100 healthy non-related individuals from the Czech population were used (C2); the results were also compared with the Genome Project data (C3). We observed shared findings of four intron (rs11564187, rs36220738, rs200829235, and rs3789329) and one exon variant (rs33995883) in the LRRK2 gene in six patients. A comparison of the C1–C3 groups revealed significant differences in haplotype frequencies between ratio of 2.09 for C1, 1.65 for C2, and 6.3 for C3, and odds ratios of 13.15 for C1, 2.58 for C2, and 7.6 for C3 were estimated. The co-occurrence of five variants in the LRRK2 gene (very probably in haplotype) could be an important potential risk factor for the development of parkinsonism, even outside the recently described pedigrees in the researched area where endemic parkinsonism is present.

Intracranial Mönckeberg’s Atherosclerosis Is Frequently Found in Autopsy Cases of Advanced Stage Malignancy with Cerebral Infarction

Cerebral infarction (CI) severely affects the prognosis of patients with malignancy. The aim of the study was to compare the pathology of CI between cases with and without malignancy focusing on intracranial Mönckeberg’s atherosclerosis. Among 778 autopsy cases of craniotomy, 53 cases of “cerebral infarction without malignancy group” (CI group), 50 cases of “malignant tumor without CI group” (MT group), and 39 cases of “cerebral infarction with malignancy group” (CM group) were identified. Mönckeberg’s atherosclerosis was mainly found in the basal ganglia and its prevalence in the CM group (38.5%) was significantly higher than in the MT group (12.0%, p = 0.005), and apparently higher than in the CI group (18.9%, p = 0.057). The CI group was significantly older, had higher BMIs, and a greater prevalence of hypertension and atrial fibrillation compared to the CM group. In addition, the prevalence of chronic renal disease was significantly lower in the CM group (2.6%, p = 0.012) than in the CI group (20.8%). Our results indicated that Mönckeberg’s atherosclerosis was often found in the basal ganglia of CM cases and that intracranial Mönckeberg’s atherosclerosis is a potential risk factor for CI in patients with advanced stage malignancy.

Response to COVID-19 mRNA vaccination in multiple myeloma is conserved but impaired compared to controls

Patients with multiple myeloma are at high risk of severe forms of COVID-19. Despite data showing diminished response to vaccine, the era of highly efficient mRNA vaccine might be a gamechanger. We sought to examine response to mRNA vaccine between healthy controls (n = 28) and multiple myeloma (MM) patients (n = 27). Response was analyzed 1 month after the second dose of anti-SARS-CoV-2 BNT162b2 vaccine. Multiple myeloma patients showed diminished levels of Anti-Spike IgG levels compared to controls, but with a high proportion of patients achieving a humoral response (89% vs. 97% in controls). Neutralizing antibodies were present in 74% of patients versus 96% of controls. Patients under current daratumumab treatment had neutralizing activity of anti-SARS-CoV-2 antibodies. Multiple myeloma patients show diminished response to SARS-COV-2 vaccine but with still high response rate. The main potential risk factor of non-response to COVID-19 vaccine was uncontrolled disease under treatment.