Abnormal sensorimotor integration is related to disease severity in Parkinson's disease: a TMS study.

Hyperexcitability of the motor system has been reported in Parkinson's disease (PD). We evaluate how cutaneous afferents modulate motor excitability in PD patients and whether abnormal modulation is correlated to parkinsonian symptoms. Digital stimulation causes abnormal enhancement of motor responses in patients. This effect may be one of the features of motor hyperexcitability in PD. Cutaneomotor hyperexcitability correlates with clinical scores, suggesting that abnormal processing of cutaneous inputs might contribute to the pathogenesis of parkinsonian symptoms.     

High resolution real-time B-mode echotomography in the diagnosis of extracranial carotid lesions. Comparison with traditional angiography

Summary Tumour growth essentially requires fibrin formation and fibrinopeptide A (FPA) is liberated into the circulation on fibrin formation. In the present study, a possible elevation of serum FPA level was examined in patients with metastatic brain tumour. A significant elevation of serum FPA level was shown in all 6 patients with metastatic brain tumour, when blood was drawn from the internal jugular vein. It was extremely high in 2 patients with rapidly growing tumour. However, such a significant elevation was not shown in 3 cancer patients without brain metastasis or in 1 patient with a huge meningioma. This suggests the possibility that the presence of metastatic brain tumour could be detected by measuring FPA in blood drawn form the internal jugular vein. This also suggests the tendency that elevation of serum FPA is higher in patients with more rapidly growing tumour.Infusion of urokinase into the internal carotid artery resulted in an elevation of serum fibrinopeptide B (1)15–42 (FPB) in 5 patients with metastatic brain tumour, when blood was drawn from the internal jugular vein. This suggests that urokinase could induce fibrinolysis in the tumour tissue, though this remains in conclusive because of the lack of complete controls.     

Lens-term- and edge-effect in X-ray grating interferometry

X-ray grating interferometry requires gratings with periods in the micrometer range and allows the acquisition of the dark-field contrast. The analyzer grating is designed to match the period of the interference pattern in order to translate it into a measurable intensity modulation. In this study, we explore the influence of a sample-induced mismatch between the interference pattern and the analyzer grating on the dark-field contrast. We propose a formula for the calculation of the signal due to a period mismatch and present estimations varying periods and detector pixel size. Furthermore, numerical simulations of the X-ray wave-front demonstrate that the wave-front curvature, described by the lens-term, e.g. behind a parabolic lens or edges of a sample can change the period of the interference pattern. Our results give a concrete explanation for the formation of a dark-field contrast from object edges and thus allow a better understanding of the dark-field signal obtained with a grating interferometer.OCIS codes: (110.7440) X-ray imaging, (340.7450) X-ray interferometry     

Brain uptake and safety of Flutemetamol F 18 injection in Japanese subjects with probable Alzheimer’s disease,subjects with amnestic mild cognitive impairment and healthy volunteers

Objective

This Phase 2 study assessed the performance of positron emission tomography (PET) brain images made with Flutemetamol F 18 Injection in detecting β-amyloid neuritic plaques in Japanese subjects.

Methods

Seventy subjects (25 with probable Alzheimer’s disease (pAD), 20 with amnestic mild cognitive impairment (aMCI), and 25 cognitively normal healthy volunteers[HVs]) underwent PET brain imaging after intravenous Flutemetamol F 18 Injection (185 MBq). Images were interpreted as normal or abnormal for neuritic plaque density by each of five non-Japanese and five Japanese readers who were blinded to clinical data. The primary efficacy analysis (based on HV and pAD data) was the agreement of the non-Japanese readers’ image interpretations with the clinical diagnosis, resulting in estimates of positive percent agreement (PPA; based on AD subjects; similar to sensitivity) and negative percent agreement (NPA; based on HVs; similar to specificity). Secondary analyses included PPA and NPA for the Japanese readers; inter-reader agreement (IRA); intra-reader reproducibility (IRR); quantitative image interpretations (standardized uptake value ratios [SUVRs]) by diagnostic subgroup; test–retest variability in five pAD subjects; and safety.

Results

PPA was 92% for all non-Japanese readers and ranged from 88 to 92% for the Japanese readers. NPA ranged from 96 to 100% for both the non-Japanese readers and the Japanese readers. The majority image interpretations (the interpretations made independently by ≥3 of 5 readers) resulted in PPA values of 92 and 92% and NPA values of 100 and 96% for the non-Japanese and Japanese readers, respectively. IRA and IRR were strong. Composite SUVR values (mean of multiple regional values) allowed clear differentiation between pAD subjects and HVs. Test–retest variability ranged from 1.14 to 2.27%, and test–retest agreement of the blinded visual interpretations was 100% for all readers. Flutemetamol F 18 Injection was generally well tolerated.

Conclusions

The detection of brain neuritic plaques in Japanese subjects using [¹⁸F]Flutemetamol PET images gave results highly consistent with clinical diagnosis, with non-Japanese and Japanese readers giving similar results. Inter-reader agreement and intra-reader reproducibility were high for both sets of readers. Visual delineation of abnormal and normal scans was corroborated by quantitative assessment, with low test–retest variability.

Trial registration

Clinicaltrials.gov registration number NCT02813070.

     

Ulnar nerve impairment at the wrist does not contribute to extramedian sensory symptoms in carpal tunnel syndrome

ObjectiveExtramedian spread of sensory symptoms is frequent in carpal tunnel syndrome (CTS) but its mechanisms are unclear. We explored the possible role of subtle ulnar nerve abnormalities in the pathogenesis of extramedian symptoms.MethodsWe recruited 350 CTS patients. After selection, 143 patients (225 hands) were included. The hand symptoms distribution was graded with a diagram into median (MED) and extramedian (EXTRAMED) pattern. We tested the correlation of ulnar nerve conduction measures with the distribution and the severity of symptoms involving the ulnar territory. The clinical significance of ulnar nerve conduction findings was explored with quantitative sensory testing (QST).ResultsEXTRAMED distribution was found in 38.7% of hands. The ulnar neurographic measures were within normal values. Ulnar nerve sensory measures were significantly better in EXTRAMED vs MED hands and not significantly correlated to ulnar symptoms severity. Ulnar and median nerve sensory measures were significantly correlated. QST showed normal function of ulnar nerve Aβ-fibers.ConclusionsUlnar nerve sensory abnormalities do not contribute to the spread of sensory symptoms into the ulnar territory.SignificanceOur data favour the hypothesis that spinal and supraspinal neuroplastic changes may underlie extramedian spread of symptoms in CTS.     

KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes

Permanent neonatal diabetes mellitus (PNDM) is a rare condition characterized by severe hyperglycemia constantly requiring insulin treatment from its onset. Complete deficiency of glucokinase (GCK) can cause PNDM; however, the genetic etiology is unknown in most PNDM patients. Recently, heterozygous activating mutations of KCNJ11, encoding Kir6.2, the pore forming subunit of the ATP-dependent potassium (K(ATP)) channel of the pancreatic beta-cell, were found in patients with PNDM. Closure of the K(ATP) channel exerts a pivotal role in insulin secretion by modifying the resting membrane potential that leads to insulin exocytosis. We screened the KCNJ11 gene in 12 Italian patients with PNDM (onset within 3 months from birth) and in six patients with non-autoimmune, insulin-requiring diabetes diagnosed during the first year of life. Five different heterozygous mutations were identified: c.149G>C (p.R50P), c.175G>A (p.V59M), c.509A>G (p.K170R), c.510G>C (p.K170N), and c.601C>T (p.R201C) in eight patients with diabetes diagnosed between day 3 and 182. Mutations at Arg50 and Lys170 residues are novel. Four patients also presented with motor and/or developmental delay as previously reported. We conclude that KCNJ11 mutations are a common cause of PNDM either in isolation or associated with developmental delay. Permanent diabetes of non autoimmune origin can present up to 6 months from birth in individuals with KCNJ11 and EIF2AK3 mutations. Therefore, we suggest that the acronym PNDM be replaced with the more comprehensive permanent diabetes mellitus of infancy (PDMI), linking it to the gene product (e.g., GCK-PDMI, KCNJ11-PDMI) to avoid confusion between patients with early-onset, autoimmune type 1 diabetes.     

Levels of liver enzymes and urea in rats naturally infected with larval forms of Taenia taeniformis

The aim of this study was to investigate the changes in the levels of liver enzymes and urea associated with an outbreak of cysticercosis (Taenia taeniformis) in rat liver. At the end of a previous trial, the animals were euthanized and necropsied when cysts of T. taeniformis were found. The number of cysts ranged from ten to 30 per rat liver. Blood samples were collected from ten rats with cysticercoids (from 12 to 22 cysts) and from ten non-affected rats that were kept in another animal house. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urea values were reduced when compared with non-parasitized animals; alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) values were increased. Since the current experiment had to be repeated due to hepatic impairment evidenced by reduced ALT, AST, and urea values and increased ALP and GGT values, this study aims to alert the scientific community to the importance of sanitary barriers in animal housing.     

Co-expression of Epstein-Barr virus latent membrane protein and vimentin in “aggressive” histological subtypes of Hodgkin's disease

Summary The presence of Epstein-Barr virus (EBV) genome in Hodgkin's and Reed-Sternberg (HRS) cells, as detected using in situ hybridization (ISH) with biotinylatedBamHI V probes, along with the expression of EBV-encoded latent membrane protein (LMP) and vimentin was examined in paraffin-embedded sections of 39 immunomorphologically characterized cases of Hodgkin's disease (HD). ISH demonstrated EBV in HRS cells in 15 of 39 cases, whereas LMP expression was detected in 11 of 39 cases, only in the presence of EBV genome detection. With the exception of 1 case, in which HRS cells expressed B-cell-associated antigens, the LMP-positive cases included specimens in which HRS cells were of non-B, non-T phenotype. LMP expression showed a stronger association with lymphocyte depletion (LD) (3/3) and mixed cellularity (MC) (6/11) than with lymphocyte predominance (0/5) or nodular sclerosis (2/20) subtypes. Vimentin expression on HRS cells was found in all the LMP-expressing cases and only in a fraction (13/28) of LMP-negative cases. This study supports the view that HD represents a heterogeneous group of diseases also in terms of EBV association, LMP expression being strongly related to the aggressive LD and MC histological subtypes. In light of the supposed interactions between vimentin and LMP, their coexpression on HRS cells, as detected in this study, provides further evidence for a significant role of EBV in the development of a proportion of HD cases.