ABSTRACT
Many pathogenic genes have been identified in early-onset Parkinson′s disease, but the early-onset Parkinson′s disease with 22q11.2 deletion has not been reported in Chinese. A case of early-onset Parkinson′s disease with 22q11.2 deletion was confirmed by whole-exome sequencing-based copy number variation detection in Fujian Medical University Union Hospital. This article reports its clinical characteristics and discusses its pathogenesis, diagnosis and treatment management.
ABSTRACT
Objective:To evaluate the sleep disorders in patients with Parkinson′s disease (PD) with different onset sides, and to analyze the correlation between PD kinesia-onset side and sleep disorders.Methods:A total of 658 patients with primary PD admitted to the Special Outpatient Department of Parkinson′s disease in Fujian Medical University Union Hospital from January 2015 to March 2021 were collected. According to the onset side of motor symptoms, they were divided into the left group (313 cases) and the right group (345 cases). The medical history collection and physical examination were conducted to evaluate the motor symptoms, non-motor symptoms [Non-Motor Symptom Scale (NMSS)], depression state and cognitive function of the patients. Parkinson′s Disease Sleep Sclale-2 (PDSS-2) and the Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) were used to evaluate and analyze their sleep status, and comparisons were made between groups. Binary multivariate Logistic regression analysis was used to access the risk factors associated with sleep disorders in Parkinson′s disease.Results:The scores of daytime fatigue [2.00(0, 4.00)] and unexplained limb pain [4.00(0, 4.00)] in NMSS assessment of PD patients in the left onset group were significantly higher than those in the right onset group [1.00(0, 3.00), Z=-2.545, P=0.001; 2.00(0, 4.00), Z=-2.797, P=0.005]. There was no significant difference in the total score of PDSS-2 between the two groups, but there were significant differences in limb restlessness, periodic limb activity, muscle spasm and early drowsiness between the two groups. In the evaluation of rapid eye movement sleep behavior disorder (RBD), the total score of RBDSQ in the left onset group [2.00(0, 4.00)] was significantly higher than that in the right onset group [1.00(0, 3.00), Z=-4.363, P<0.001]. The incidence of dream content, nocturnal behavior, nocturnal exercise, self-injury and bed partner in dream, abnormal behavior at night, nighttime awakening, dream memory and sleep disorder in the left onset group was also higher than that in the right onset group. In addition, binary multivariate Logistic regression showed that PD-related sleep disorders were associated with onset of advanced age ( OR=1.037, 95% CI 1.018-1.057, P<0.001), course of disease ( OR=1.014, 95% CI 1.010-1.018, P<0.001) and onset of abnormal postural gait ( OR=1.505,95% CI 1.058-2.141, P=0.023). RBD in patients with PD was associated with left onset ( OR=2.215,95% CI 1.395-3.515, P=0.001), advanced age onset ( OR=1.045,95% CI 1.019-1.072, P=0.001) and course of disease ( OR=1.014,95% CI 1.009-1.019, P<0.001). Conclusions:PD patients with left onset are more likely to have sleep disorders such as limb restlessness, periodic limb activity, muscle spasm and early drowsiness. At the same time, the incidence and severity of RBD in patients with left onset of PD are significantly higher than those of patients with right onset of PD. The onset side of motor symptoms of PD is an important factor affecting sleep disorders, and the onset of left side may be a risk factor for PD patients with RBD.
ABSTRACT
Objective:To investigate the clinical manifestations of familial amyloid multiple neuropathy (FAP) caused by Ala117Ser mutation, and to improve the clinical recognition of FAP.Methods:The clinical manifestations, electrophysiological examination, pathology and gene mutation characteristics of a case of FAP, who admitted to Fujian Medical University Union Hospital on November 25, 2014, were analyzed, and the literatures on the FAP cases caused by Ala117Ser mutation were reviewed and summarized.Results:The patient was a 59-year-old male from Fujian province. The first symptom was numbness in the extremities, followed by obvious autonomic nerve symptoms and motor disorder, and fatal cardiac dysfunction occurred in the later stage of the disease. The skin biopsy showed amyloidosis, and transthyretin gene analysis indicated the mutation of c.349G>T p.Ala117Ser. The clinical manifestations of FAP caused by Ala117Ser mutation reported in literatures are consistent with this case. And the reported FAP cases in China are concentrated in southern regions such as Fujian Province and Guangdong Province.Conclusions:Ala117Ser mutation in FAP patients is usually late onset and clinically manifested as multiple sensorimotor peripheral neuropathy, accompanied by prominent autonomic symptoms. The distribution of the patients has significant regional characteristics. Histopathological and genetic tests for the clinical diagnosis are of great significance.
ABSTRACT
Objective To investigate the possible effect of ginsenoside Rg1 and oligo Aβ1-42 on PKA/CREB pathway.Methods The damage was induced by oligomeric Aβ1-42 in primary cortical neuron.Neurons were incubated with or without glutamate,or incubated in Aβ,or pre-incubated in Rg1 and then co-incubated in Aβ.The proteins of p-CREB,t-CREB,PKA Ⅱ α and BDNF were detected by Western blot.Results After the treatment with Oligo Aβ1-42 for 2 h,the p-CREB/t-CREB level induced by glutamate was obviously lower (P＜ 0.001).However,in neurons pre incubatedwith 2.5,5.0,10.0 μmol/L of ginsenoside Rg1 and then co-incubated with 5μmol/L of oligo Aβ1-42,the p-CREB/t-CREB induced by glutamate was significantly increased as compared with that of Aβ1-42 group (P＜0.05).Upon Aβ1-42 exposure for 2 h,cortical neurons showed a statistically significant increase in PKA Ⅱ α as compared to the control group (P ＜ 0.001).Pre-treatmentwith varying doses of ginsenoside Rg1 (2.5,5,10μmol/L) showed a decrease in PKA Ⅱ α as compared to neurons treated with Aβ1-42 alone for 2 h (P＜0.001).Furthermore,BDNF level significantly increased in Rgl-pretreated cells as compared to cells treated with Aβ1-42 alone for 24h (P＜0.05).Conclusions Ginsenoside Rg1 attenuates the oligo Aβ142 inhibition of PKA/CREB pathway.
ABSTRACT
Objective To systematically assess the efficacy of memantine on moderate to severe Alzheimer's disease (AD).Methods With the evaluation method of the Cochrane system,searches were made in the Cochrane Library,MEDLINE,Embase,Forest Laboratories,CNKI,Wanfang Data,and VIP Data up to February 2013 for double blind,randomized,and placebo-controlled trials (RCTs) evaluating the efficacy of memantine for moderate to severe AD.A meta-analysis of included clinical trials was conducted using the Revman 5.2 software to evaluate the efficacy of memantine on overall clinical status,cognitive function activities of daily living,and behavioral and psychological disturbances.Results A total of 8 RCTs were included (2 527 patients with moderate to severe AD).Results of the meta-analysis showed that,for patients with moderate to severe AD,memantine had better efficacy than placebo on overall clinical status,cognitive function,and activities of daily living (MD=-0.24,95％CI:0.340.15;SMD=-0.26,95％CI:-0.340.18;SMD=-0.13,95％CI:-0.21-0.05),but there was no significant difference in efficacy on behavioral and psychological function between memantine and placebo (P =0.08).Analysis of subgroups showed that memantine had better efficacy than placebo on cognitive function in moderate AD patients (SMD =-0.22,95％CI:-0.37 0.06) and on overall clinical status,cognitive function,and activities of daily living in severe AD patients (MD-0.29,95％CI:-0.40 0.18;SMD=-0.31,95％CI:0.46-0.15;SMD=-0.16,95％ CI:-0.25 0.06;MD=-3.13,95％ CI:-4.88-1.39;respectively).Conclusions Memantine has efficacy on overall clinical status,cognitive function and activities of daily living in patients with moderate to severe AD,especially in patients with severe AD.
ABSTRACT
Aim To explore the possible protective effect of ginsenoside Rg1 on oligomeric Aβ1-42 induced apoptosis and its possible mechanism. Methods The damage was induced by oligomeric Aβ1-42 in primary cortical neurons. Cells were incubated in the absence or presence of Aβ, or co-incubated in sp600125 with Aβ, or pre-incubated in ginsenoside Rg1 then co-incu-bated in Aβ. The p-JNK, JNK, caspase-3 activity and TUNEL-positive cells were detected. Results In Aβ1-42 treated group, the ratio of p-JNK/JNK level was increased more than that in non-treated group for 15 min. However, in neurons preincubated with (2. 5, 5, 10 μmol·L-1 ) ginsenoside Rg1 and then co-incuba-ted with 5 μmol·L-1 oligomeric Aβ1-42 , the p-JNK/JNK ratio, caspase-3 activity and TUNEL positive neu-rons were significantly decreased compared with those of Aβ1-42 treated group. Conclusion Ginsenoside Rg1 can attenuate the oligomeric Aβ1-42-induced apop-tosis by JNK pathway.