Transcranial sonography in patients with Parkinson's disease with glucocerebrosidase mutations

ObjectivesThe aim of this study was to search for possible differences in the findings of transcranial sonography (TCS) between groups of patients with glucocerebrosidase (GBA)-associated Parkinson's disease (PD) (4 patients with Gaucher disease type 1 and parkinsonism [GD+PD+] and 18 PD patients with heterozygous GBA mutations; [GBA+PD+]) and groups of 12 patients with Gaucher disease type 1 and no signs of parkinsonism (GD+PD?), 9 asymptomatic carriers of heterozygous GBA mutations (GBA+PD?), 32 sporadic PD patients (sPD), and 43 healthy controls.ResultsIn all groups of patients, except asymptomatic carriers of heterozygous GBA mutations (mean ± SD: 0.16 ± 0.03 cm²), the maximal areas of substantia nigra hyperechogenicity (aSN-max) was higher (GD+PD+: 0.28 ± 0.15 cm²; GD+PD?: 0.18 ± 0.06 cm²; GBA+PD+: 0.27 ± 0.06 cm²; sPD: 0.28 ± 0.10 cm²) when compared to controls (0.12 ± 0.08 cm²) (p = 0.001). In GBA-associated PD (GD+PD+ and GBA+PD+) and sPD, aSNmax values were very similar. Moderate or marked SN hyperechogenicity was present in 87.5% of sPD patients and in 83% of PD patients with heterozygous GBA mutations, but in only 11.6% of controls, and in 22.2% and 33.3% of patients from GBA+PD? and GD+PD? groups, respectively (p < 0.001). The prevalence of interrupted or missing echogenicity of the brainstem raphe differed between the groups (p = 0.046), while no difference was observed in the diameter of the third ventricle.ConclusionsTCS findings in GBA-associated PD were consistent to those of patients with sporadic PD.     

Acute presentation of a solid pseudopapillary tumor of the pancreas

We report a case of acute presentation of a solid pseudopapillary tumor of the pancreas in a young boy who had suffered a blunt abdominal trauma. Urgently performed CT examination and repeated ultrasound revealed a subhepatic mass, which gradually increased in size, but the imaging features were not specific enough to permit a precise diagnosis. Because signs of peritoneal irritation and increased circulatory instability gradually developed within the hours of observation, the decision was made to perform an urgent exploratory laparotomy. The exploration revealed a hematoperitoneum and a large hematoma-like subhepatic bleeding mass. Further exploration showed that this mass was a tumor arising from the head of the pancreas, which had ruptured on the surface. A curative pancreatoduodenectomy was performed. Pathohistological examination of the resected specimen revealed a solid pseudopapillary tumor of the pancreas, an extremely rare tumor predominantly occurring in adolescent girls and in young adult women. It has a favorable prognosis if resected radically. The boy in our report is feeling well 36 months after the operation.     

Assessment of health-related quality of life in patients with myasthenia gravis in Belgrade (Serbia)

The aim of this study was to assess factors that might influence the health-related quality of life (HRQoL) in patients with myasthenia gravis (MG). A cross-sectional study was performed including 230 consecutive patients with MG. Severity of the disease was estimated according to the MGFA classification and QMG score. HRQoL was assessed by the SF-36 questionnaire. Depressive and anxiety symptoms were assessed using the Hamilton rating scales for depression and anxiety, respectively. Social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS), and acceptance of the disease by the Acceptance of Illness Scale. The significant demographic predictors of worse HRQoL in MG patients were older age (p?=?0.025) and lower education (p?=?0.012). Among clinical features, significant independent contributing factors of worse HRQoL were more severe form of the disease according to MGFA (p?=?0.001) and higher QMG score (p?=?0.001). Finally, psychosocial predictors of worse quality of life were lower MSPSS score (p?=?0.001), poor acceptance of the disease (p?=?0.001), as well as higher levels of anxiety and depression (p?=?0.001). Our study revealed that the HRQoL in patients with MG is similarly reduced in its psychological and physical aspects. These results may have a practical implication pointing out that different aspects of psychosocial support should be added to the regular therapeutic protocols.     

NKG2D ligands mediate immunosurveillance of senescent cells

Cellular senescence is a stress response mechanism that limits tumorigenesis and tissue damage. Induction of cellular senescence commonly coincides with an immunogenic phenotype that promotes self-elimination by components of the immune system, thereby facilitating tumor suppression and limiting excess fibrosis during wound repair. The mechanisms by which senescent cells regulate their immune surveillance are not completely understood. Here we show that ligands of an activating Natural Killer (NK) cell receptor (NKG2D), MICA and ULBP2 are consistently up-regulated following induction of replicative senescence, oncogene-induced senescence and DNA damage - induced senescence. MICA and ULBP2 proteins are necessary for efficient NK-mediated cytotoxicity towards senescent fibroblasts. The mechanisms regulating the initial expression of NKG2D ligands in senescent cells are dependent on a DNA damage response, whilst continuous expression of these ligands is regulated by the ERK signaling pathway. In liver fibrosis, the accumulation of senescent activated stellate cells is increased in mice lacking NKG2D receptor leading to increased fibrosis. Overall, our results provide new insights into the mechanisms regulating the expression of immune ligands in senescent cells and reveal the importance of NKG2D receptor-ligand interaction in protecting against liver fibrosis.     

Comparison of the clinical and cognitive features of genetically positive ALS patients from the largest tertiary center in Serbia

Discovering novel mutations in C9orf72, FUS, ANG, and TDP-43 genes in ALS patients arises necessities for better clinical characterizations of these subjects. The aim is to determine clinical and cognitive profile of genetically positive Serbian ALS patients. 241 ALS patients were included in the study (17 familiar and 224 apparently sporadic). The following genes were analyzed: SOD1, C9orf72, ANG, FUS, and TDP-43. An extensive battery of classic neuropsychological tests was used in 27 ALS patients (22 SOD1 positive and 5 SOD1 negative) and 82 healthy controls (HCs). Overall 37 (15.4%) of 241 ALS patients carried mutations in tested genes—among 17 familiar ALS patients 16 (94.1%) were positive and among 224 apparently sporadic 21 (9.4%) had causative mutation. Mutations in SOD1 gene were the most common, representing 27 (73.0%) of all genetically positive ALS patients. The main clinical characteristics of SOD1 positive patients were: spinal onset in lower extremities, common sphincter and sensitive disturbances, and dysexecutive syndrome. Within SOD1 positive patients, we noticed somewhat earlier onset in patients with A145G, sensory and sphincter disturbances were dominant in patients with L144F, while D90A patients had significant sensory involvement. SOD1 negative group consisted of ten (27.0%) patients (six C9orf72, two ANG, one TDP-43, and one patient baring triple FUS, C9orf72 expansion, and ANG variants). Bulbar involvement and more extensive neuropsychological impairment (including executive, visuospatial, and memory difficulties) were the main features of SOD1 negative cohort. Our results suggest that meaningful clinical suspicion of certain ALS genotype might be made based on thorough clinical evaluation of patients.     

Employment status of patients with chronic inflammatory demyelinating polyradiculoneuropathy

It has been previously shown that patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are unemployed or retired have worse quality of life. The aim of this study was to assess predictors of early retirement in CIDP. One hundred five patients with CIDP were included. Following measures were used: questionnaire on employment status, Medical Research Council Sum Score, INCAT disability score, Beck Depression Inventory, and Krupp's Fatigue Severity Scale. At the moment of testing, 2% of patients were students, 15% were employed, 9% were unemployed due to CIDP, 9% were unemployed but not due to CIDP, 28% were retired early due to disability caused by CIDP, and finally 37% were in old‐age pension. Mean age when patients retired due to CIDP was 50 ± 8 years. Mean time from CIDP onset to retirement was 2.7 ± 2.3 years. Older age at onset, lower education, and more severe weakness at the time of diagnosis were significant predictors of early retirement due to CIDP. Retired patients were 12 times more likely to suffer from depression, compared to employed patients (OR = 12.2, 95% CI = 1.41‐100, P < 0.01), and eight times more likely to have fatigue (OR = 8.2, 95% CI = 1.89‐35.82, P < 0.01). Older patients with lower education and more severe weakness at the time of diagnosis were most likely retired due to CIDP. Early retirement was associated with depression and fatigue. Therefore, maintaining employment should be an important aim in the management of CIDP patients.     

Neuromuscular disease‐specific questionnaire to assess quality of life in patients with chronic inflammatory demyelinating polyradiculoneuropathy

To date, generic questionnaires have been used to investigate quality of life (QoL) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients. Although these measures are very useful, they are not usually precise enough to measure all specific characteristics of the disease. Our aim was to investigate QoL using the neuromuscular disease‐specific questionnaire (individualized neuromuscular quality of life, INQoL) in a large cohort of patients with CIDP. Our study comprised 106 patients diagnosed with CIDP. INQoL questionnaire, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Visual Analogue Pain Scale, Beck Depression Inventory, and Krupp's Fatigue Severity Scale were used in our study. Physical domains of INQoL were more affected than mental, and the overall score was 57 ± 25. Significant predictors of higher INQoL score in our patients with CIDP were severe fatigue (β = 0.35, p < 0.01), higher INCAT disability score at time of testing (β = 0.29, p < 0.01), and being unemployed/retired (β = 0.22, p < 0.05). QoL was reduced in our cohort of CIDP patients, which was more pronounced in physical segments. Patients with fatigue, more severe disability, and unemployed/retired need special attention of neurologists because they could be at greater risk to have worse QoL.