Progression of Parkinson's disease is associated with gut dysbiosis: Two-year follow-up study.

BACKGROUND: We previously reported gut dysbiosis in patients with Parkinson's disease (PD). OBJECTIVE: The aim of this study is to examine whether gut dysbiosis correlates with the progression of PD. METHODS: We examined changes in gut microbiota and demographic features in 2 years in 36 PD patients. RESULTS: A change of total UPDRS scores in 2 years was predicted by the counts of Bifidobacterium and Atopobium cluster at year 0 with a correlation coefficient of 0.52. Correlation analysis additionally revealed that low counts of Bifidobacterium and Bacteroides fragilis at year 0 were associated with worsening of UPDRS I scores in 2 years. In addition, low counts of Bifidobacterium at year 0 were associated with worsening of hallucinations/delusions in 2 years. Similarly, low counts of B. fragilis at year 0 were associated with worsening of motivation/initiative in 2 years. The patients were evenly divided into the deteriorated and stable groups based on the degree of worsening of total UPDRS scores. The deteriorated group had lower counts of Bifidobacterium, B. fragilis, and Clostridium leptium than the stable group at year 0 but not at year 2, suggesting that the deteriorated group may demonstrate accelerated lowering of these bacteria at year 0. CONCLUSIONS: The total counts of intestinal bacterial decrease in the course of PD progression. Temporal profiles of lowering of bacterial counts are likely to be different from bacteria to bacteria, and also between the deteriorating and stable groups, which may be able to be exploited to differentiate patients with rapidly and slowly progressive PD pathology.

Association between changes in visual evoked magnetic fields and non-motor features in Parkinson's disease.

Visual dysfunction can be caused by several abnormalities, including dysfunctions in the visual cortex and retina. Our aim was to investigate changes in visual evoked brain responses in the primary visual cortex associated with Parkinson's disease (PD). Sixteen healthy control subjects and ten patients with PD participated in this study. We assessed the visual evoked magnetic field (VEF) using magnetoencephalography (MEG). Checkerboard pattern reversal (CPR) and monotonous grating pattern (MGP) stimulations were used. Magnetic resonance imaging (MRI) was performed to analyze brain volume and generate a tractogram. Cognitive and olfactory function, and Unified Parkinson's Disease Rating Scale (UPDRS) scores were evaluated in patients with PD. Four components of the VEF (1M, 2M, 3M, 4M) were observed following stimulation. For both stimuli, results from the 1M and 2M components were significantly greater and the latency of the 1M component was increased markedly in the PD group compared with the healthy control group. In the PD group, 1M latency correlated with the UPDRS score of 1 for both stimuli, and a correlation was observed between olfactory function and the UPDRS score of 3 for the CPR stimulation alone. We suggest that the conduction delay observed following visual stimulation occurs peripherally rather than in the primary visual cortex. Degeneration of selective elements of the visual system in the retina, possibly midget cells, may be involved.

Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson's Disease.

BACKGROUND: The intestine is one of the first affected organs in Parkinson's disease (PD). PD subjects show abnormal staining for Escherichia coli and α-synuclein in the colon. METHODS: We recruited 52 PD patients and 36 healthy cohabitants. We measured serum markers and quantified the numbers of 19 fecal bacterial groups/genera/species by quantitative RT-PCR of 16S or 23S rRNA. Although the six most predominant bacterial groups/genera/species covered on average 71.3% of total intestinal bacteria, our analysis was not comprehensive compared to metagenome analysis or 16S rRNA amplicon sequencing. RESULTS: In PD, the number of Lactobacillus was higher, while the sum of analyzed bacteria, Clostridium coccoides group, and Bacteroides fragilis group were lower than controls. Additionally, the sum of putative hydrogen-producing bacteria was lower in PD. A linear regression model to predict disease durations demonstrated that C. coccoides group and Lactobacillus gasseri subgroup had the largest negative and positive coefficients, respectively. As a linear regression model to predict stool frequencies showed that these bacteria were not associated with constipation, changes in these bacteria were unlikely to represent worsening of constipation in the course of progression of PD. In PD, the serum lipopolysaccharide (LPS)-binding protein levels were lower than controls, while the levels of serum diamine oxidase, a marker for intestinal mucosal integrity, remained unchanged in PD. CONCLUSIONS: The permeability to LPS is likely to be increased without compromising the integrity of intestinal mucosa in PD. The increased intestinal permeability in PD may make the patients susceptible to intestinal dysbiosis. Conversely, intestinal dysbiosis may lead to the increased intestinal permeability. One or both of the two mechanisms may be operational in development and progression of PD.

Disinhibitory shift of recovery curve of somatosensory-evoked response in elderly: A magnetoencephalographic study.

OBJECTIVE: The aim of the study was to investigate the functional differences between N20m and P30m components of somatosensory-evoked magnetic cortical field (SEF) in young and senior subjects. METHODS: Twenty-nine healthy subjects, 13 younger (mean age: 21.8years) and 16 senior (63.8 years), participated. Magnetic fields were measured using a 160-channel, whole head MEG. Single- and paired-pulse stimulations of 200 artifact-free MEG signal epochs were averaged separately. We calculated how aging affects recovery function of SEFs. RESULTS: The senior showed a prolonged N20m peak latency compared to the younger, although the P30m peak latency was not significantly different between groups. The N20m ratios at 60 and 80 ms in the senior were significantly increased compared to the ratios in the younger (60 ms: P<0.05, 80 ms: P<0.001). The P30m ratios at inter-stimulus interval (ISI) of 80 and 100 ms showed even disinhibition in the senior than in the younger (P<0.05). The younger also showed a significantly negative correlation between P30m and N20m components' recovery curves (R=0.72, P<0.05). CONCLUSION: Aging-related changes that occurred in recovery functioning were the decrease in N20m component suppression and the increase in P30m component recovery, indicating that the N20m and P30m components have different functions in aging-related recovery changes. SIGNIFICANCE: Our results show that the N20m ratio at an ISI of 80 ms was significantly increased in the senior group, indicating that the second stimulus-evoked SEF was less inhibited by the initial stimulus at this ISI, suggesting less refractory effect or increased disinhibition.

Results of orbital preservation for advanced malignant maxillary sinus tumors.

OBJECTIVE: The purpose of the study was to examine the oncological and functional outcomes of multimodality therapy for patients with advanced malignant maxillary sinus tumors that invaded the orbit. STUDY DESIGN: Retrospective study. METHODS: The medical records of 26 patients with orbital invasion were retrospectively analyzed. The patient group consisted of 16 men and 10 women, with a median age of 58 years. The mean follow-up period was 73 months. The most common disease was squamous cell carcinoma. Seven patients had nodal disease. All patients underwent simultaneous combined therapy consisting of conservative surgery through a sublabial incision, radiotherapy, and regional chemotherapy. Patients with nodal disease were treated with either irradiation or selective neck dissection. RESULTS: The 5- and 10-year overall survival rates were 68% and 51%, respectively. The 5- and 10-year local control rates were 66% and 51%, respectively. Overall survival rates and local control rates were significantly worse in patients with disease other than squamous cell carcinoma. Local control rates were significantly worse in patients with orbital apex disease than in patients without orbital apex disease. All 26 patients, despite orbital involvement, retained their orbital contents. Nineteen of these patients demonstrated adequate ocular function. CONCLUSIONS: Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy is an effective method for local control and preservation of ocular function. However, performing orbital conservation procedure in patients with disease other than squamous cell carcinoma and with orbital apex disease must be considered carefully.