Carpets with visual cues can improve gait in Parkinson's disease patients: may be independent of executive function.

BACKGROUND: Gait impairment is common in Parkinson's disease (PD) patients, which greatly reduces their quality of life. Executive dysfunction is associated with gait impairment. Compensatory strategies, including visual cues, have been shown to be effective in improving PD gait. In this study, we aimed to understand whether carpets with visual cues could improve PD gait, and how the improvement varies across patients with different executive function state. METHODS: We designed carpets with chessboard and stripe cues. A total of 65 Chinese PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, L-dopa equivalent daily dosage, Hoehn & Yahr stage, Frontal Assessment Battery, Mini Mental State Examination Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were evaluated. Gait parameters including stride length, gait speed and fall risk were recorded by a wearable electronic device. RESULTS: The stride length and gait speed were significantly improved and the fall risk was significantly mitigated when PD patients walked on carpets with chessboard and stripe patterns. Further analysis showed the amelioration of gait parameters was independent of executive dysfunction. CONCLUSIONS: Our study demonstrates that carpets with visual cues can improve the gait of PD patients even in those with mild executive dysfunction.

Isolated unilateral oculomotor palsy caused by pure midbrain infarction: a case report.

Purpose: Multiple etiologies may cause oculomotor nerve palsies. Identification of different etiologies is very important for subsequent treatment. Midbrain infarction is a rare cause of oculomotor nerve palsy. Materials and methods: We herein present a case of isolated unilateral oculomotor paresis caused by pure midbrain infarction. Results: Her pupillary sphincter and inferior rectus muscles were selectively spared. The symptoms were completely relieved after two months of antiplatelet therapy. We proposed that fibers from Edinger-Westphal nucleus and inferior rectus nucleus do not course through the paramedian area of the midbrain. Conclusions: Our report adds to the understanding of fascicles arrangement in the midbrain.

Neck pain and absence of cranial nerve symptom are clues of cervical myelopathy mimicking stroke: Two case reports.

BACKGROUND: Cervical myelopathy is a potential stroke imitator, for which intravenous thrombolysis would be catastrophic. CASE SUMMARY: We herein present two cases of cervical myelopathy. The first patient presented with acute onset of right hemiparesis and urinary incontinence, and the second patient presented with sudden-onset right leg monoplegia. The initial diagnoses for both of them were ischemic stroke. However, both of them lacked cranial nerve symptom and suffered neck pain at the beginning of onset. Their cervical spinal cord lesions were finally confirmed by cervical computed tomography. A literature review showed that neck pain and absence of cranial nerve symptom are clues of cervical myelopathy. CONCLUSION: The current report and the review remind us to pay more attention to these two clues in suspected stroke patients, especially those within the thrombolytic time window.

Case report: Blepharospasm in peak-dose dyskinesia may benefit from amantadine in Parkinson's disease.

Introduction: Blepharospasm is uncommon in Parkinson's disease, especially in the peak-dose dyskinesia period. Case presentation: We herein present the case of a patient with PD who developed blepharospasm in the peak-dose dyskinesia period. The symptom was improved by taking amantadine. Conclusion: The current report expands the phenomenology of peak-dose dykinesia in PD to include dystonic blepharospasm. This complication of levodopa therapy may respond to amantadine despite the dystonic appearance of movements.

Parkinsonism-Hyperpyrexia Syndrome and Dyskinesia-Hyperpyrexia Syndrome in Parkinson's Disease: Two Cases and Literature Review.

Parkinsonism-hyperpyrexia syndrome (PHS) and dyskinesia-hyperpyrexia syndrome (DHS) are rare but exhibit life-threatening complications in Parkinson's disease (PD). We herein presented two cases of PD patients and performed a comprehensive and comparative literature review for these two syndromes. The first case was diagnosed as PHS with cerebral salt wasting syndrome caused by abrupt withdrawal of antiparkinsonian medication. Her symptoms were gradually remitted with reinstitution of the medication. The second one was an early-stage PD patient diagnosed as DHS in association with abuse of antiparkinsonian drugs. Her symptoms were gradually remitted with reduced dosage of dopaminergic drugs. Results of literature reviews revealed a total of 56 and 13 cases of PHS and DHS, respectively, and they were more likely to occur in elderly and long-term PD patients. These two syndromes showed different female-to-male ratio, similar mortality, and different recovery time. There were stark differences between PHS and DHS, including triggers (abrupt drug stoppage versus drug abuse), symptoms (worsened tremor and rigidity versus continuous dyskinesia), and treatment (drug reinstitution versus drug reduction). In summary, our reports and the review provide new insights into PHS and DHS in association with PD and may facilitate rapid discrimination of the syndromes for timely and proper treatment to reduce mortality.

ALDH1A1 Genetic Variations May Modulate Risk of Parkinson's Disease in Han Chinese Population.

Background: Studies in animal models have suggested that aldehyde dehydrogenase 1 (encoded by ALDH1A1) protects against Parkinson's disease (PD) by reducing toxic metabolites of dopamine. Herein we aimed to investigate whether ALDH1A1 was genetically associated with PD susceptibility in humans. Methods: A Han Chinese population of 1,039 subjects was recruited to analyze six tag-single nucleotide polymorphisms (SNPs), followed by haplotype analyses and variants interaction analyses. Real-time PCR was used to analyze mRNA levels of ALDH1A1 in peripheral blood of 42 subjects. Results: The tag-SNP rs7043217 of ALDH1A1 was significantly associated with PD susceptibility with the T serving as a risk allele (genotype frequency, P = 0.030; allele frequency, P = 0.013, OR = 1.258, 95% CI = 1.050-1.508). Multiple haplotypes were linked to abnormalities of PD risk, topped by a 4-SNP GGTA module in the order of rs4646547, rs1888202, rs7043217, and rs647880 (P = 9.610 × 10-8, OR = 6.420, 95% CI = 2.944-13.998). Interaction analyses showed that a simultaneous presence of the CC genotype of rs7043217 and the TT genotype of ALDH2 variant rs4767944 conferred an elevated protection against PD (P = 4.68 × 10-4, OR = 0.378, 95% CI = 0.219-0.652). The mRNA expression of ALDH1A1 showed a trend of reduction (P = 0.084) in PD patients compared to the controls. Conclusion: Our results provide novel genetic insights into the role of ALDH1 in PD pathogenesis.

DNA Methyltransferase 1 Is Dysregulated in Parkinson's Disease via Mediation of miR-17.

Aberrant DNA methylation is closely associated with the pathogenesis of Parkinson's disease (PD). DNA methyltransferases (DNMTs) are the enzymes for establishment and maintenance of DNA methylation patterns. It has not been clearly defined how DNMTs respond in PD and what mechanisms are associated. Models of PD were established by treatment of five different neurotoxins in cells and intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Plasma samples of PD patients were also used. Western blot, real-time PCR, immunostaining, and/or luciferase reporter were employed. DNA methylation was analyzed by the bisulfite sequencing analysis. Protein expression of DNMT1, but not of DNMT3A and DNMT3B, was reduced in the cellular and mouse models of PD. Paradoxically, mRNA levels of DNMT1 were increased in these models. After ruling out the possibility of protein degradation, we screened a set of miRNAs that potentially targeted DNMT1 3'-UTR by luciferase reporters and expression abundancies. miR-17 was identified for further investigation with miR-19a of low expression as a parallel comparison. Although exogenous transfection of either miR-17 or miR-19a mimics could inhibit DNMT1 expression, results of miRNA inhibitors showed that miR-17, but not miR-19a, endogenously regulated DNMT1 and the subsequent DNA methylation. Furthermore, levels of miR-17 were elevated in the neurotoxin-induced PD models and the plasma of PD patients. This study demonstrates that the miR-17-mediated DNMT1 downregulation underlies the aberrant DNA methylation in PD. Our results provide a link bridging environmental insults and epigenetic changes and implicate miR-17 in therapeutical modulation of DNA methylation in PD.

Structural Analysis and Antioxidant Activity of Extracellular Polysaccharides Extracted from Culinary-Medicinal White Jelly Mushroom Tremella fuciformis (Tremellomycetes) Conidium Cells.

Using Tremella fuciformis conidium cells for submerged fermentation is a cost-effective way to harvest bioactive compounds. In this study, we emphasized the structural and functional analysis of extracellular polysaccharides (EPS) extracted from T. fuciformis conidium cells. An EPS high-yield strain tyc63 was selected and a 6-day optimum fermentation period was determined. Crude EPS was extracted and three high molecular weight (5189, 171.6, and 661 kDa) polysaccharides TFP-1, TFP-2, and TFP-3 were isolated and purified. TFP-1 is mainly composed of glucose, xylose, mannose, and fucose, while both TFP-2 and TFP-3 are mainly composed of rhamnose, arabinose, mannose, galactose, and glucose. FT-IR analysis revealed that TFP-1, TFP-2, and TFP-3 have typical polysaccharide structure. The antioxidant assay revealed that the crude EPS, TFP-1, TFP-2, and TFP-3 presented high free radical scavenging activities but low ferric reducing power, suggesting that the EPS produced by liquid fermentation could be used as a potent radical scavenger.

Structural characterization and immune-enhancing activity of a novel high-molecular-weight polysaccharide from Cordyceps militaris.

A novel homogeneous polysaccharide (CMP-III) was extracted and purified from C. militaris. Structural characterization revealed that CMP-III had an average molecular weight of 4.796 × 104 kDa and consisted of glucose, mannose and galactose with the molar ratio of 8.09:1.00:0.25. The main linkage types of CMP-III consisted of 1 â†’ 4)-α-D-Glc (70.08%), 1 â†’ 4,6)-α-D-Man (9.59%), 1→)-α-D-Man (10.79%) and 1 → 2,6)-α-D-Gal (3.93%) based on methylation and NMR analysis. The immunomodulatory assay indicated that CMP-III significantly promoted macrophage phagocytosis and secretion of NO, TNF-α and IL-6. Further study suggested that macrophage activated by CMP-III involved mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-B (NF-κB) signaling pathways. Overall, these results suggested that CMP-III could be developed as a potent immunomodulatory agent for use in functional foods and dietary supplements.

Association analyses of variants of SIPA1L2, MIR4697, GCH1, VPS13C, and DDRGK1 with Parkinson's disease in East Asians.

A recent large-scale European-originated genome-wide association data meta-analysis followed by a replication study identified 6 new risk loci for Parkinson's disease (PD), which include rs10797576/SIPA1L2, rs117896735/INPP5F, rs329648/MIR4697, rs11158026/GCH1, rs2414739/VPS13C, and rs8118008/DDRGK1. However, whether these new loci are associated with PD in Asian populations remain elusive. The INPP5F is nonpolymorphic in Asians. The present study aimed to understand the effects of the other 5 new loci in a Han Chinese population comprising 579 sporadic PD patients and 642 controls. Significant associations with PD were observed in the variants of SIPA1L2 (p = 0.001) and VPS13C (p = 0.007), where the T (odd ratio [OR] = 1.484, 95% confidence interval [CI] 1.186-1.858) and A (OR = 1.362, 95% CI 1.087-1.707) alleles serve as the risk alleles, respectively. The genotype distributions in the SIPA1L2 and VPS13C variants were also different between the patients and controls (p = 0.002 and p = 0.023, respectively). In contrast, no significant association with PD was found in the variants of MIR4697, GCH1, and DDRGK1 either in allele or genotype frequencies. Noteworthy, a followed meta-analysis of East Asian studies suggested an association of the GCH1 variant with PD (p = 0.04, OR 1.08, 95% CI 1.00-1.16), while the other results are in line with those of our cohort. In conclusion, our study together with meta-analyses demonstrates that the variants of SIPA1L2 and VPS13C, potentially GCH1, but not of MIR4697 and DDRGK1, are associated with PD susceptibility in East Asians.

Mitochondrial DNA variants modulate genetic susceptibility to Parkinson's disease in Han Chinese.

It is well recognized that mitochondrial dysfunction is involved in the pathogenesis of Parkinson's disease (PD). The mtDNA displacement loop (D-loop) region is known to accumulate structural alterations and mutations. To understand how mtDNA variants contribute to the susceptibility to sporadic PD in Chinese, a total of 500 PD patients and 505 controls were recruited from East China, and their D-loop regions were sequenced. A total of 389 variants were detected out of the 1005 subjects. There were 91 variants with frequencies >1%, which included 88 single nucleotide polymorphisms (SNPs), 2 deletions and 1 insertion. Amongst, 6 SNPs were significantly associated with sporadic PD. Specifically, the SNPs 151T/C, 189G/A, 16086C/T and 16271C/T contributed to increased susceptibility, while 318C/T and 16134T/C were associated with reduced risk for PD. Further analyses of mtDNA haplogroups and their risk for PD occurrence showed that subjects carrying haplogroup A5 were susceptible while haplogroup B5 carriers were more resistant to the disease. In summary, our study for the first time systematically analyzed mtDNA variants by sequencing the D-loop region in a Chinese population to understand their associations with PD. These results demonstrate that mtDNA variants modulate risk for sporadic PD.