Search

A rare, benign congenital lymphangioma has been reported to occur frequently in the neck and axilla, but rarely in the retroperitoneal space. We report a case of a retroperitoneal lymphangioma associated with hypoproteinemia caused by protein-loss into the tumor. In this case, lymphoscintigraphy with subcutaneously injected Tc-99m-human serum albumin (HSA) disclosed the communication between the tumor and the lymphatic system, and sequential abdominal scintigraphy with intravenously injected Tc-99m-HSA revealed the protein loss into the tumor. Abdominal scintigraphy with Tc-99m-HSA injected intravenously or subcutaneously is occasionally useful for determining the etiology of hypoproteinemia. [ABSTRACT FROM AUTHOR]

Background: The genus Aeromonas is increasingly implicated in human infections, but knowledge of its clinical characteristics and antimicrobial resistance profiles has been limited owing to its complex taxonomy., Methods: We conducted a multicenter prospective cohort study of patients with Aeromonas infections at hospitals across Japan. Patients were eligible for inclusion if they had an Aeromonas spp. strain in a clinical culture and were considered infected at the culture site. Clinical data were collected, and isolates underwent susceptibility testing and whole-genome sequencing., Results: A total of 144 patients were included. Hepatobiliary infection accounted for a majority of infections (73% [105 of 144]), which mostly occurred in elderly patients with comorbid conditions, including hepatobiliary complications. The all-cause 30-day mortality rate was 10.0% (95% confidence interval, 4.9%-14.8%). By whole-genome sequencing, 141 strains (98%) belonged to 4 Aeromonas species -A caviae , A hydrophila , A veronii , and A dhakensis- with significant intraspecies diversity. A caviae was predominant in all infection sites except skin and soft tissue, for which A hydrophila was the prevailing species. The genes encoding chromosomally mediated class B, C, and D β-lactamases were harbored by 92%-100% of the isolates in a species-specific manner, but they often lacked association with resistance phenotypes. The activity of cefepime was reliable. All isolates of A hydrophila and A dhakensis carried an mcr-3- like colistin resistance gene and showed reduced susceptibility to colistin., Conclusions: Hepatobiliary tract was the most common infection site of Aeromonas spp., with A caviae being the dominant causative species. The resistance genotype and phenotype were often incongruent for β-lactam agents., Competing Interests: Potential conflicts of interest. M. S. has received a grant and honoraria from KANTO Chemical. S. H. has received a grant from Shionogi and honoraria from Shionogi, MSD, Daiichi Sankyo, and NISSUI Pharmaceutical. Y. D. has received grants from Entasis and Shionogi and has consulted for Moderna, Gilead, Shionogi, Fujifilm, Meiji Seika Pharma, Pfizer, AbbVie, MSD, Gilead, and bioMerieux. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Spinocerebellar degenerations (SCDs) are a diverse group of rare and slowly progressive neurological diseases that include spinocerebellar ataxia type 1 (SCA1), SCA2, SCA3, SCA6, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and multiple system atrophy (MSA). They are often inherited, and affect the cerebellum and related pathways. The combination of clinical findings and lesion distribution has been the gold-standard for classifying SCDs. This conventional approach has not been very successful in providing a solid framework shared among researchers because their points of views have been quite variable. After identification of genetic abnormalities, classification was overwhelmed by genotyping, replacing the conventional approach far behind. In this review, we describe a stepwise operational approach that we constructed based only on macroscopic findings without microscopy to classify SCDs into three major groups: pure cerebellar type for SCA6 and SCA31; olivopontocerebellar (OPC) type for SCA1, SCA2, SCA7 and MSA; and dentatorubral-pallidoluysian (DRPL) type for SCA1, SCA3, DRPLA and progressive supranuclear palsy (PSP). Spinocerebellar tract involvement distinguishes SCA1 and SCA3 from DRPLA. Degeneration of the internal segment of the pallidum is accentuated in SCA3 and PSP, while degeneration of the external segment is accentuated in SCA1 and DRPLA. These contrasts are helpful in subdividing OPC and DRPL types to predict their genotypes. Lesion distribution represents disease-specific selective vulnerability, which is readily differentiated macroscopically using our stepwise operational approach. Precise prediction of the major genotypes will provide a basis to understand how genetic abnormalities lead to corresponding phenotypes through disease-specific selective vulnerabilities., (© 2022 Japanese Society of Neuropathology.)

We report two patients with autosomal dominant neuronal intranuclear inclusion disease (NIID) harboring the biallelic GGC repeat expansion in NOTCH2NLC to uncover the impact of repeat expansion zygosity on the clinical phenotype. The zygosity of the entire NOTCH2NLC GGC repeat expansion and DNA methylation were comprehensively evaluated using fluorescent amplicon length PCR (AL-PCR), Southern blotting and targeted long-read sequencing, and detailed genetic/epigenetic and clinical features were described. In AL-PCR, we could not recognize the wild-type allele in both patients. Targeted long-read sequencing revealed that one patient harbored a homozygous repeat expansion. The other patient harbored compound heterozygous repeat expansions. The GGC repeats and the nearest CpG island were hypomethylated in all expanded alleles in both patients. Both patients harboring the biallelic GGC repeat expansion showed a typical dementia-dominant NIID phenotype. In conclusion, the biallelic GGC repeat expansion in two typical NIID patients indicated that NOTCH2NLC-related diseases could be completely dominant., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Spinocerebellar ataxia type 2 (SCA2) is caused by mutations in the ATXN2 gene in which toxic effects are triggered by expanded polyglutamine repeats within ataxin-2. SCA2 is accompanied by motor neuron degeneration as occurs in amyotrophic lateral sclerosis (ALS). We investigated the distribution patterns of ataxin-2 and transactivation-responsive DNA-binding protein 43 (TDP-43), a major disease-related protein in ALS, in the CNS of 3 SCA2 patients. Phosphorylated TDP-43 (pTDP-43)-positive lesions were widely distributed throughout the CNS and generally overlapped with 1C2 (expanded polyglutamine)-immunoreactive lesions. This distribution pattern is different from the pattern in limbic-predominant age-related TDP-43 encephalopathy. In SCA2, double immunostaining of TDP-43 and 1C2 in motor neurons revealed 3 staining patterns: cytoplasmic 1C2 and nuclear TDP-43, nucleocytoplasmic 1C2 and nuclear TDP-43, and nuclear 1C2 and cytoplasmic TDP-43, which reflect the early, active, and final stages of pathological change, respectively. The translocation of TDP-43 from the nucleus to the cytoplasm along with the translocation of 1C2 in the opposite direction indicates that nuclear accumulation of the disease-specific protein ataxin-2 affects the intracellular dynamics of TDP-43. Such a close interrelationship between mutant ataxin-2 and TDP-43 in the cell might account for the similarity of their distribution in the CNS of patients with SCA2., (© 2022 American Association of Neuropathologists, Inc. All rights reserved.)

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slow-progressing multisystem neurodegenerative disorder. Biallelic AAGGG repeat expansion in RFC1 has been identified as causative of this disease, and repeat conformation heterogeneity (ACAGG repeat) was also recently implied. To molecularly characterize this disease in Japanese patients with adult-onset ataxia, we accumulated and screened 212 candidate families by an integrated approach consisting of flanking PCR, repeat-primed PCR, Southern blotting and long-read sequencing using Sequel II, GridION or PromethION. We identified 16 patients from 11 families, of whom seven had ACAGG expansions [(ACAGG)exp/(ACAGG)exp] (ACAGG homozygotes), two had ACAGG and AAGGG expansions [(ACAGG)exp/(AAGGG)exp] (ACAGG/AAGGG compound heterozygotes) and seven had AAGGG expansions [(AAGGG)exp/(AAGGG)exp] (AAGGG homozygotes). The overall detection rate was 5.2% (11/212 families including one family having two expansion genotypes). Long-read sequencers revealed the entire sequence of both AAGGG and ACAGG repeat expansions at the nucleotide level of resolution. Clinical assessment and neuropathology results suggested that patients with ACAGG expansions have similar clinical features to previously reported patients with homozygous AAGGG expansions, although motor neuron involvement was more notable in patients with ACAGG expansions (even if one allele was involved). Furthermore, a later age of onset and slower clinical progression were implied in patients with ACAGG/AAGGG compound heterozygous expansions compared with either ACAGG or AAGGG homozygotes in our very limited cohort. Our study clearly shows the occurrence of repeat conformation heterogeneity, with possible different impacts on the affected nervous systems. The difference in disease onset and progression between compound heterozygotes and homozygotes might also be suspected but with very limited certainty due to the small sample number of cases in our study. Studies of additional patients are needed to confirm this., (© The Author(s) (2022). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The basal ganglia and related dopaminergic cortical areas are important neural systems underlying motor learning and are also implicated in impulse control disorders (ICDs). Motor learning impairments and ICDs are frequently observed in Parkinson's disease (PD). Nevertheless, the relationship between motor learning ability and ICDs has not been elucidated., Methods: We examined the relationship between motor learning ability and gambling propensity, a possible symptom for prodromal ICDs, in PD patients. Fifty-nine PD patients without clinical ICDs and 43 normal controls (NC) were administered a visuomotor rotation perturbation task and the Iowa Gambling Task (IGT) to evaluate motor learning ability and gambling propensity, respectively. Participants also performed additional cognitive assessments and underwent brain perfusion SPECT imaging., Results: Better motor learning ability was significantly correlated with lower IGT scores, i.e., higher gambling propensity, in PD patients but not in NC. The higher scores on assessments reflecting prefrontal lobe function and well-preserved blood perfusion in prefrontal areas were correlated with lower IGT scores along with better motor learning ability., Conclusions: Our findings suggest that better motor learning ability and higher gambling propensity are based on better prefrontal functions, which are in accordance with the theory that the prefrontal cortex is one of the common essential regions for both motor learning and ICDs.

Background: Anticoagulation therapy, especially using heparin or recently developed oral direct factor Xa inhibitors (DiXals), is recommended as first-line treatment for cancer-related venous thromboembolism (VTE). However, the preventive efficacy of these anticoagulants for cancer-associated ischemic stroke is still unknown. We retrospectively investigated the efficacy of subcutaneous unfractionated heparin (UFH) and DiXals for preventing the recurrence of cancer-associated cryptogenic ischemic stroke with VTE., Methods: We retrospectively studied consecutive patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE who received subcutaneous UFH or oral DiXaIs at 9 hospitals., Result: Fifty-three patients (24 treated with UFH and 29 treated with DiXaIs) were enrolled. Of these, 47 demonstrated systemic metastasis (cancer stage IV). During 30-day follow-up after initiation of anticoagulation therapy, recurrent ischemic stroke was observed in only 1 patient (4%) in the UFH group and in 9 patients (31%) in the DiXal group. The incidence of major bleeding complications was similar between the 2 groups (4% and 10%, respectively). The cumulative risk of ischemic stroke recurrence within 30 days was lower with UFH than with DiXals (competing risk analysis, p = 0.008). In the DiXal group, patients who experienced recurrence showed significantly higher D-dimer levels than those without recurrence., Conclusion: In patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE, UFH demonstrated a lower rate of recurrent ischemic stroke than DiXaIs, and there were no differences in bleeding risk between the 2 treatments. D-dimer levels at stroke onset increased the risk of recurrence in the DiXal group but not in the UFH group., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Intracellular aggregates are a common pathological hallmark of neurodegenerative diseases such as polyglutamine (polyQ) diseases, amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple system atrophy (MSA). Aggregates are mainly formed by aberrant disease-specific proteins and are accompanied by accumulation of other aggregate-interacting proteins. Although aggregate-interacting proteins have been considered to modulate the formation of aggregates and to be involved in molecular mechanisms of disease progression, the components of aggregate-interacting proteins remain unknown. In this study, we showed that small glutamine-rich tetratricopeptide repeat-containing protein alfa (SGTA) is an aggregate-interacting protein in neurodegenerative diseases. Immunohistochemistry showed that SGTA interacted with intracellular aggregates in Huntington disease (HD) cell models and neurons of HD model mice. We also revealed that SGTA colocalized with intracellular aggregates in postmortem brains of patients with polyQ diseases including spinocerebellar ataxia (SCA)1, SCA2, SCA3, and dentatorubral-pallidoluysian atrophy. In addition, SGTA colocalized with glial cytoplasmic inclusions in the brains of MSA patients, whereas no accumulation of SGTA was observed in neurons of PD and ALS patients. In vitro study showed that SGTA bound to polyQ aggregates through its C-terminal domain and SGTA overexpression reduced intracellular aggregates. These results suggest that SGTA may play a role in the formation of aggregates and may act as potential modifier of molecular pathological mechanisms of polyQ diseases and MSA.

We herein report a 33-year-old woman who was an asymptomatic hepatitis B virus (HBV) carrier and presented with distal muscle weakness in the legs and asymmetrical paresthesia in the distal extremities. A nerve biopsy specimen revealed fibrinoid necrosis associated with inflammatory infiltration in the perineural space, and deposition of hepatitis B core antigen and C4d complement was detected in the vascular endothelial cells as well as around the vessels. She was diagnosed with HBV-related vasculitic neuropathy and treated with intravenous immunoglobulin (IVIG). Her symptoms completely subsided after eight weeks. Vasculitic neuropathy rarely develops in the chronic inactive stages of HBV infection. This is the first report of an HBV-inactive carrier with vasculitic neuropathy successfully treated with IVIG.