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Cognitive impairment in adult patients with moyamoya disease (MMD) is sometimes overlooked and can occur in patients with no ischemic or hemorrhagic lesions. Better profiling and reliable diagnostic methods that characterize the group and associate the impairments and pathology of MMD are required in order to deliver appropriate treatments and support. The potential of 123I-iomazenil single-photon emission computed tomography (SPECT) for this issue has been reported in some studies, but the universality of this method remains unclear. A multicenter study of adult patients (aged 18-60 years) with MMD who experienced difficulties in social lives despite normal activities of daily living was implemented to delineate the common characteristics of this group of patients. In this study, iomazenil SPECT, besides patient characteristics, cognitive functions, and conventional imaging, was acquired to examine whether this method is suitable as a universal diagnostic tool. A total of 36 patients from 12 institutes in Japan were included in this study. Domain scores of world health organization quality of life 26 indicated low self-rating in physical health and psychological domains. The percentages of patients who had

To effectively treat cerebral arteriovenous malformations (AVMs), peri-nidal flow regulation and metabolic status must be understood. In this study, we used 15O-oxygen positron emission tomography (PET) post-processing analysis to investigate vascular radioactivity in the nidal region of AVMs. Single-dynamic PET imaging was performed on seven unruptured AVM patients during the sequential inhalation of 15O2 and C15O2. A previously validated dual-tracer basis function method (DBFM) was employed to calculate parametric images. The results of our study were as follows. First, in remote and contralateral AVM regions, DBFM and a previous approach of dual-tracer autoradiography (DARG) showed strong positive correlations in cerebral blood flow ( CBF ), cerebral oxygen metabolism rate ( CMRO2), and oxygen extraction fraction. Second, peri-nidal CBF and CMRO2 correlation was lower, and overestimation occurred with DARG compared to with DBFM. Third, on comparing DBFM to quantitative 123I-iodoamphetamine single-photon emission computed tomography (SPECT), CBF correlated significantly. In contrast, the correlation between DARG and quantitative 123I-iodoamphetamine-SPECT was weaker in the peri-nidal regions. Fourth, analysis of tissue time-activity curves demonstrated good reproducibility using the novel formulation in the control, peri-nidus, and core nidal regions, indicating the adequacy of this approach. Overall, the DBFM approach holds promise for assessing haemodynamic alterations in patients with AVMs. [ABSTRACT FROM AUTHOR]

Clostridioides difficile is a major cause of infectious nosocomial diarrhea in high-income countries (1). Disease severity ranges from asymptomatic colonization to fulminant colitis, sometimes leading to colectomy and death (2). [...]

Abstract Background Hashimoto’s disease has reportedly been associated with stroke; however, cerebrovascular morphology and clinical course remain poorly documented. The present study aimed to determine the angiographic features and clinical outcomes of intracranial arterial stenosis (IAS) associated with Hashimoto’s disease in a retrospective cohort. Methods Overall, 107 adult patients with IAS were screened for anti-thyroid antibodies; of these, 26 patients tested positive. The 42 affected hemispheres were classified into subgroups according to the steno-occlusion site and the development of abnormal collateral (moyamoya) vessels. These subgroups were dichotomized into moyamoya vessels positive (MM type) and negative (non-MM type). The initial presentation, IAS progression, and vascular events during the follow-up period were compared. Results The following sites of stenosis were identified: the bifurcation of the internal carotid artery in 11 (26.2%), M1 or A1 in 29 (69.0%), and more distal (M2-M4/A2-A4) in 2 (4.8%) hemispheres. Further, 17 hemispheres were categorized into the MM type and 25 were classified into the non-MM type. During the follow-up period (mean 2.5 years), IAS progression was identified in 8 (32%) hemispheres of the non-MM type and 0 (0%) hemispheres of the MM type (p = 0.041). Ischemic attacks occurred in 5 (20.0%) hemispheres of the non-MM type (4.6%/year) and 0 hemispheres of the MM type (p = 0.08). Further, 4 (23.5%) hemispheres of the MM type experienced intracerebral hemorrhage, whereas none of the non-MM type hemorrhaged (p = 0.012). Conclusions Hashimoto’s disease-associated IAS exhibits various angiographic morphologies, resulting in different clinical presentations. Screening for anti-thyroid antibodies and careful management based on vascular morphology appears important in adults with IAS.

Abstract Background Limb-girdle muscular dystrophy (LGMD) is a genetically heterogeneous, hereditary disease characterized by limb-girdle weakness and histologically dystrophic changes. The prevalence of each subtype of LGMD varies among different ethnic populations. This study for the first time analyzed the phenotypes and genotypes in Taiwanese patients with LGMD in a referral center for neuromuscular diseases (NMDs). Results We enrolled 102 patients clinically suspected of having LGMD who underwent muscle biopsy with subsequent genetic analysis in the previous 10 years. On the basis of different pathological categories, we performed sequencing of target genes or panel for NMDs and then identified patients with type 1B, 1E, 2A, 2B, 2D, 2I, 2G, 2 N, and 2Q. The 1B patients with LMNA mutation presented with mild limb-girdle weakness but no conduction defect at the time. All 1E patients with DES mutation exhibited predominantly proximal weakness along with distal weakness. In our cohort, 2B and 2I were the most frequent forms of LGMD; several common or founder mutations were identified, including c.1097_1099delACA (p.Asn366del) in DES, homozygous c.101G > T (p.Arg34Leu) in SGCA, homozygous c.26_33dup (p.Glu12Argfs*20) in TCAP, c.545A > G (p.Tyr182Cys), and c.948delC (p.Cys317Alafs*111) in FKRP. Clinically, the prevalence of dilated cardiomyopathy in our patients with LGMD2I aged > 18 years was 100%, much higher than that in European cohorts. The only patient with LGMD2Q with PLEC mutation did not exhibit skin lesions or gastrointestinal abnormalities but had mild facial weakness. Muscle imaging of LGMD1E and 2G revealed a more uniform involvement than did other LGMD types. Conclusion Our study revealed that detailed clinical manifestation together with muscle pathology and imaging remain critical in guiding further molecular analyses and are crucial for establishing genotype–phenotype correlations. We also determined the common mutations and prevalence for different subtypes of LGMD in our cohort, which could be useful when providing specific care and personalized therapy to patients with LGMD.

Maintenance hemodialysis (MHD) patients display reduced daily physical activity (DPA) and physical performance (PP). Previous studies did not differentiate the effects of kidney failure and MHD treatments from comorbidities as causes for reduced DPA and PP. In relatively healthy MHD patients and normal adults, we evaluated DPA and PP and examined relationships between DPA and PP and possible associations between anxiety or depression and DPA and PP. DPA, 6-minute walk distance (6-MWD), sit-to-stand (STS), and stair-climbing tests were measured in 72 MHD patients (40% diabetics) with limited comorbidities and 39 normal adults of similar age and gender mix. Anxiety and depression were measured by the Beck anxiety and depression inventories. DPA, time-averaged over 7 days, and all 3 PP tests were impaired in MHD patients, to about 60% to 70% of normal values (P < .0001 for each measurement). MHD patients spent more time sleeping or physically inactive (P < .0001) and less time in ≥ moderate activity (P < .0001). Adjusted DPA correlated with 6-MWD but not STS or stair-climbing. Anxiety and depression were identified in 43% and 33% of MHD patients and 2.5% and 5.1% of normals (P < .0001 for each comparison). Most of the impairment in DPA and PP tests were also observed in MHD patients without anxiety or depression. However, MHD patients with both anxiety and depression generally had the most impaired DPA and PP. In MHD patients, higher adjusted anxiety scores were correlated with impaired 6-MWD and STS, whereas adjusted average DPA was negatively correlated with depression (r = -0.33, P = .006) but not anxiety. DPA on the hemodialysis day (P = .01), day after dialysis (P = .03), and day 2 after dialysis (P = .03) each correlated negatively with degree of depression but not with anxiety. MHD patients displayed negative-adjusted correlations between anxiety and 6-MWD (P = .03) and STS (P = .04). In relatively healthy MHD patients, DPA and PP are substantially impaired and correlated with each other, even in patients without evidence for anxiety or depression. Anxiety and depression are common in MHD patients and are associated with further impairment in DPA and PP.

The Arase satellite observed the precipitation of monoenergetic electrons accelerated from a very high altitude above 32,000 km altitude on 16 September 2017. The event was selected in the period when the high‐angular resolution channel of the electron detector looked at pitch angles within ∼5° from the ambient magnetic field direction, and thereby was the first to examine the detailed distribution of electron flux near the energy‐dependent loss cone at such high altitudes. The potential energy below the satellite estimated from the observed energy‐dependence of the loss cone was consistent with the energy of the upgoing ion beams, indicating that ionospheric ions were accelerated by a lower‐altitude acceleration region. The accelerated electrons inside the loss cone carried a significant net field‐aligned current (FAC) density corresponding to ionospheric‐altitude FAC of up to ∼3μA/m2. Based on the anisotropy of the accelerated electrons, we estimated the height of the upper boundary of the acceleration region to be >∼2 RE above the satellite. The height distribution of the acceleration region below the satellite, estimated from the frequency of auroral kilometric radiation, was ∼4,000–13,000 km altitude, suggesting that the very‐high‐altitude acceleration region was separated from the lower acceleration region. Additionally, we observed time domain structure (TDS) electric fields on a subsecond time scale with a thin FAC indicated by magnetic deflections. Such a TDS may be generated by the formation of double layers in the magnetotail, and its potential drop could significantly contribute (∼40%–60%) to the parallel energization of precipitating auroral electrons. Plain Language Summary: The auroral arc is produced by electrons in the magnetosphere accelerated downward by a quasi‐static electric field. The region of the electric field, so called the auroral acceleration region, is typically located just above the ionosphere, at altitudes of a few thousand kilometers. However, recent studies have shown that it can be extended to altitudes higher than 30,000 km. The mechanism and impact of such a very‐high‐altitude acceleration region remain a mystery. The high‐angular resolution electron detector on board the Arase satellite successfully measured current and energy flows carried by the electron accelerated at the very‐high‐altitude acceleration region above the satellite altitude of 32,000 km. This acceleration at very‐high‐altitudes contributed significantly to the energy flow into the ionosphere. Based on the anisotropy of the accelerated electrons, the frequency of auroral kilometric radiation, and the presence of spiky electrostatic waves, we estimate that the very‐high‐altitude acceleration region was located more than 12,000 km above the satellite as a thin charge separation layer, apart from the acceleration region below the satellite. Our results suggest that localized electric fields at very high altitudes, which were not previously associated with the aurora, can energize auroral electrons and affect auroral visibility. Key Points: We comprehensively analyzed a very‐high‐altitude (>32,000 km) auroral acceleration eventNet precipitation of accelerated electrons significantly contributes to the field‐aligned current and energy flux into the ionosphereDouble layers in the magnetotail are possible candidates for very‐high‐altitude auroral accelerations [ABSTRACT FROM AUTHOR]

Point mutations at m.8993T>C and m.8993T>G of the mtDNA ATPase 6 gene cause the neurogenic weakness, ataxia and retinitis pigmentosa (NARP) syndrome, a mitochondrial disorder characterized by retinal, central and peripheral neurodegeneration. We performed detailed neurological, neuropsychological and ophthalmological phenotyping of a mother and four daughters with NARP syndrome from the mtDNA m.8993T>C ATPase 6 mutation, including 3-T brain MRI, spectral domain optical coherence tomography (SD-OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), electromyography and nerve conduction studies (EMG-NCS) and formal neuropsychological testing. The degree of mutant heteroplasmy for the m.8993T>C mutation was evaluated by real-time allele refractory mutation system quantitative PCR of mtDNA from hair bulbs (ectoderm) and blood leukocytes (mesoderm). There were marked phenotypic differences between family members, even between individuals with the greatest degrees of ectodermal and mesodermal heteroplasmy. 3-T MRI revealed cerebellar atrophy and cystic and cavitary T2 hyperintensities in the basal ganglia. SD-OCT demonstrated similarly heterogeneous areas of neuronal and axonal loss in inner and outer retinal layers. AOSLO showed increased cone spacing due to photoreceptor loss. EMG-NCS revealed varying degrees of length-dependent sensorimotor axonal polyneuropathy. On formal neuropsychological testing, there were varying deficits in processing speed, visual-spatial functioning and verbal fluency and high rates of severe depression. Many of these cognitive deficits likely localize to cerebellar and/or basal ganglia dysfunction. High-resolution retinal and brain imaging in NARP syndrome revealed analogous patterns of tissue injury characterized by heterogeneous areas of neuronal loss.

Abstract Background 15O-oxygen inhalation PET is unique in its ability to provide fundamental information regarding cerebral hemodynamics and energy metabolism in man. However, the use of 15O-oxygen has been limited in a clinical environment largely attributed to logistical complexity, in relation to a long study period, and the need to produce and inhale three sets of radiopharmaceuticals. Despite the recent works that enabled shortening of the PET examination period, radiopharmaceutical production has still been a limiting factor. This study was aimed to evaluate a recently developed radiosynthesis/inhalation system that automatically supplies a series of 15O-labeled gaseous radiopharmaceuticals of C15O, 15O2, and C15O2 at short intervals. Methods The system consists of a radiosynthesizer which produces C15O, 15O2, and C15O2; an inhalation controller; and an inhalation/scavenging unit. All three parts are controlled by a common sequencer, enabling automated production and inhalation at intervals less than 4.5 min. The gas inhalation/scavenging unit controls to sequentially supply of qualified radiopharmaceuticals at given radioactivity for given periods at given intervals. The unit also scavenges effectively the non-inhaled radioactive gases. Performance and reproducibility are evaluated. Results Using an 15O-dedicated cyclotron with deuteron of 3.5 MeV at 40 μA, C15O, 15O2, and C15O2 were sequentially produced at a constant rate of 1400, 2400, and 2000 MBq/min, respectively. Each of radiopharmaceuticals were stably inhaled at

PurposeThis study was designed to assess the effect of mitochondrial DNA (mtDNA) mutation T8993C on cone structure in a family expressing neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome.MethodsFive family members were studied, using clinical examination, nerve conduction studies, perimetry, optical coherence tomography (OCT) measures of central retinal thickness, and electroretinography. High-resolution images of cone structure using adaptive optics scanning laser ophthalmoscopy (AOSLO) were obtained in four subjects with stable fixation. Cone spacing was compared to 18 age-similar normal subjects and converted to z-scores at each location where unambiguous cones were identified. Tissue levels of T8993C mutant heteroplasmy in blood and hair follicles were quantified using real-time allele-refractory mutations system (ARMS) quantitative polymerase chain reaction (qPCR).ResultsSubjects expressing the T8993C mutation showed varying levels of disease severity. The subject with the lowest mutant load (42%-54%) showed no neurologic or retinal abnormalities. The remaining four subjects with over 77% mutant load all expressed severe neurologic and/or retinal abnormalities. AOSLO images revealed three patterns of cone spacing: pattern 1, normal; pattern 2, increased cone spacing within a contiguous cone mosaic; and pattern 3, patchy cone loss with increased cone spacing. Visual function was most severely affected in pattern 3.ConclusionsHigh levels of T8993C mutant load were associated with severe neurologic or visual dysfunction, while lower levels caused no detectable abnormalities. Visual function was better in patients with a contiguous and regular cone mosaic. Patients expressing high levels of the mtDNA T8993C mutation show abnormal cone structure, suggesting normal mitochondrial DNA is necessary for normal waveguiding by cones.