Cognitive dysfunction and mental fatigue in childhood chronic fatigue syndrome--a 6-month follow-up study

Objectives: Cognitive function was investigated in patients with childhood type chronic fatigue syndrome (CCFS) using the modified advanced trail making test (mATMT). Methods: mATMT was performed on 19 patients with CCFS and 25 healthy controls of comparable age and sex. The effectiveness of combined treatment with cognitive behavioral therapy (CBT) and pharmacotherapy and its relationship to cognitive function was investigated by evaluation of Chalder’s fatigue scale and behavior state before and after treatment for 6 consecutive months. Results: All three tasks (motor skill, selective and alternative attention, and spatial working memory) of the mATMT, especially the difference in reaction time of the alternative attention task, could discriminate CCFS patients from control subjects with 70.5% accuracy (P = 0.007). CCFS patients showed significantly lower alternative attention and Chalder’s fatigue score before treatment (P = 0.037 and 0.002, respectively). A significant improvement in performance status scores was found during the 6 months follow-up period with combined treatment with CBT and medication (P < 0.001). Improvement of their cognitive symptoms was significantly correlated with improvement of alternative attention (r = 0.653, P = 0.002). Conclusions: Higher-order level cognitive dysfunction affects CCFS pathogenesis. Alternative attention performance evaluated by the mATMT may be used to monitor improvement in patients with CCFS. Combined treatment with CBT and medication may be effective to improve poor attention characteristics associated with CCFS.     

Validation of Addenbrooke's cognitive examination for detecting early dementia in a Japanese population

There is a clear need for brief, but sensitive and specific, cognitive screening instruments for dementia. We assessed the diagnostic accuracy of the Japanese version of Addenbrooke's Cognitive Examination (ACE) in identifying early dementia in comparison with the conventional Mini-Mental State Examination (MMSE). Standard tests for evaluating dementia screening tests were applied. A total of 201 subjects (Alzheimer's disease (AD) = 65, frontotemporal dementia (FTD) = 24, vascular dementia = 26, dementia with Lewy bodies = 11, mild cognitive impairment (MCI) = 13, and controls = 62) participated in this study. The reliability of the ACE was very good (alpha coefficient = 0.82). In our patient series, the sensitivity for diagnosing dementia with an ACE score of ≤ 74 was 0.889 with a specificity of 0.987, and the sensitivity of an ACE score of ≤ 80 was 0.984 with a specificity of 0.867. The Japanese version of the ACE is a very accurate instrument for the detection of early dementia, and should be widely used in clinical practice.     

Phosphorylated TDP-43 pathology and hippocampal sclerosis in progressive supranuclear palsy

TDP-43 is characteristically accumulated in TDP-43 proteinopathies such as frontotemporal lobar degeneration and motor neurone disease, but is also present in some tauopathies, including Alzheimer’s disease, argyrophilic grain disease, and corticobasal degeneration (CBD). However, several studies have suggested that cases of progressive supranuclear palsy (PSP) lack TDP-43 pathology. We have therefore examined limbic regions of the brain in 19 PSP cases, as well as in 12 CBD cases, using phosphorylation-dependent anti-TDP-43 antibodies. We observed TDP-43-positive inclusions in five PSP cases (26%), as well as in two CBD cases (17%). The amygdala and hippocampal dentate gyrus were most frequently affected in PSP. Regional tau burden tended to be higher in TDP-43-positive PSP cases, and a significant correlation between tau and TDP-43 burden was noted in the occipitotemporal gyrus. Hippocampal sclerosis (HS) was found in 3/5 TDP-43-positive PSP cases, but HS was significantly more frequent in TDP-43-positive than TDP-43 negative PSP cases. Dementia was present in 13/19 (58%) of the PSP cases, in 4/5 TDP-43-positive cases, in all 3 TDP-43-positive cases with HS, in 1/2 TDP-43-positive cases without HS, and 7/14 cases lacking both. TDP-43 and tau were frequently colocalized in the amygdala, but not in the hippocampal dentate gyrus. Immunoblotting demonstrated the characteristic (for TDP-43 proteinopathies) 45 and 25 kDa bands and high molecular weight smear in the TDP-43-positive PSP case. These findings suggest that (1) although PSP is nominally a tauopathy, pathological TDP-43 can accumulate in the limbic system in some cases, and (2) TDP-43 pathology may be concurrent with HS.     

Inhibition of the adhesive ability of Streptococcus mutans on hydroxyapatite pellet using a toothbrush equipped with TiO2 semiconductor and solar panel

TiO₂ has an antibacterial effect against Streptococcus mutans (S. mutans). The objective of this study was to show the Inhibition of the adhesive ability of S. mutans on hydroxyapatite pellet using a toothbrush equipped with TiO₂ semiconductor and solar panel. Gradual brushing of 9 hydroxyapatite pellets was done by the same person using a solar toothbrush under 750/LUX light source in water. As a control, pellets brushed with a placebo toothbrush were done using the same procedure by the same person. All the pellets were inoculated in 10 ml Brain Heart Infusion (BHI) broth containing 100μl of 10⁸ CFU/ml S. mutans and 1% sucrose and then incubated at 37°C for 12 hours. After incubation, the adherence conditions of S. mutans on each pellet were checked. The bacterial count of S. mutans on the brushed pellets using solar toothbrush were fewer than those using placebo toothbrush. The quantities of adherence of S. mutans decreased according to number of brushing and adhesion on pellets brushed more than 50 times could not be recognized. However, adhesion of S. mutans on the pellets brushed using placebo toothbrush were recognized and the adhesive quantities were visually the same. These results occurred because of some electronic charges on the brushed pellets using solar toothbrush. Soladey-3 toothbrush prevented S. mutans adhesion to the hydroxyapatite pellet under a light source.     

Contribution of germline mutations to PARK2 gene inactivation in lung adenocarcinoma

Homozygous germline mutations of the PARK2 gene are responsible for the development of early-onset Parkinson's disease (PD). Homozygous PARK2 mutations have been also detected in lung adenocarcinoma (LADC). However, since heterozygous PARK2 germline mutations are present in a subset of non-PD individuals, the timing for the occurrence of two-hit PARK2 mutations in LADC progression is unclear. Therefore, we comprehensively analyzed mutations, expression and copy number variations of the PARK2 gene in 267 primary LADCs together with the corresponding noncancerous lung cells and 39 LADC cell lines. Heterozygous germline exonic deletions were detected in five patients with LADC, and loss of heterozygosity including the PARK2 locus was detected in 31/267 (11.6%) LADCs. However, homozygous PARK2 inactivation was not detected in any of them, including the five patients with germline mutations. Homozygous PARK2 inactivation was detected in 6/39 (15%) cell lines, two exonic deletions, one exonic duplication, and three point mutations, while heterozygous PARK2 inactivation was detected in two cell lines (both by exonic deletions). These results strongly indicate that somatic PARK2 mutations occur rarely (or do not occur) in LADC development and that germline PARK2 mutations could contribute to LADC progression but not to LADC development.     

Optimal scanning protocol of arterial dominant phase for hypervascular hepatocellular carcinoma with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MR

Purpose:

To investigate optimal delay time of hepatic arterial phase in Gadoxetate‐enhanced MR for detecting hypervascular hepatocellular carcinoma (HCC).

Materials and Methods:

Forty‐five patients with 85 hypervascular HCCs and 9 patients with 16 hypervascular HCCs underwent Gadoxetate‐ and Gd‐DTPA‐enhanced MR at 1.5 Tesla (T) system, respectively. All HCCs were analyzed 10–38 s after injection using a time‐resolved dynamic MR sequence with keyhole data sampling. Seven sequential phase images (1 phase = 4 s) were obtained during a single breath hold of 28 s. Time–intensity curves of the abdominal aorta, liver parenchyma, and HCC were obtained, then aortic contrast arrival time, time of peak HCC enhancement, duration time of HCC and aortic enhancement, and time delay from aortic contrast arrival to peak enhancement of HCC were measured.

Results:

Aortic contrast arrival time was 15.1 ± 2.9 s, time of peak HCC enhancement 29.9 ± 4.6 s, duration time of HCC enhancement 17.4 ± 6.4 s postinjection of Gadoxetate. Duration of aortic enhancement (23.6 ± 3.5 s) of Gadoxetate‐enhanced MR was significantly less than that of Gd‐DTPA‐enhanced MR (26.3 ± 2.8 s) (P < 0.0059).

Conclusion:

Peak enhancement time of HCC on Gadoxetate‐enhanced MR imaging occurred at 14.6 ± 4.6 s after aortic contrast arrival. J. Magn. Reson. Imaging 2011;33:864–872. © 2011 Wiley‐Liss, Inc.     

Diagnostic performance of percutaneous core needle lung biopsy under multi-CT fluoroscopic guidance for ground-glass opacity pulmonary lesions

Objective

The diagnostic performance of percutaneous core needle lung biopsy under multi-CT fluoroscopic guidance for ground-glass opacity (GGO) pulmonary lesions was evaluated.

Materials and methods

Out of 90 patients who underwent CT fluoroscopy-guided core needle biopsy of GGO lesions at our institution, the biopsy results and the final diagnoses were retrospectively compared in 67 patients with available data (one lesion per patient). Diagnostic performance was also compared according to the lesion size (≤10 mm (n = 8) versus 11-20 mm (n = 42) versus >20 mm (n = 17)), the percentage of GGO component (50-90% (n = 31) versus >90% (n = 36)), and the length of needle path (≤7 cm (n = 45) versus >7 cm (n = 22)). Finally, all 90 cases were reviewed for complications.

Results

The overall sensitivity, specificity, and accuracy were 97%, 100%, and 97%, respectively. The diagnostic sensitivity and accuracy tended to be lower in smaller lesions (≤10 mm; 86 and 88%, 11-20 mm; 97 and 98%, >20 mm; 100 and 100%, respectively, p > 0.05), and in lesions with lower percentage of GGO component (50-90%; 93 and 94%, >90%; 100 and 100%, respectively, p = 0.21), but statistical significances were not reached. The sensitivity and accuracy were not significantly affected by the length of needle path (≤7 cm; 98 and 98%, >7 cm; 95 and 96%, respectively, p = 1.00). Fourteen patients (16%) developed pneumothoraces, and 13 patients (14%) experienced mild hemoptysis, all of which resolved conservatively.

Conclusion

The diagnostic performance was satisfactory, and it was considered that the procedure was appropriate for GGO lesions regardless of lesion size, the percentage of GGO component, or the length of needle path. The procedure was also feasible without any major complications.