Effect of acute levodopa challenge test on cerebral blood flow in Parkinson's disease with the supine-to-standing transcranial Doppler test.

BACKGROUND: Levodopa, a common drug that improves symptoms of Parkinson's disease (PD), can induce a reduction in blood pressure (BP); however, the effect of levodopa on cerebral blood flow (CBF) remains unclear. OBJECTIVES: To observe the changes in BP and CBF during active standing before and after the acute levodopa challenge test (ALCT) and analyse the influencing factors of CBF in patients with PD. METHODS: BP and CBF velocity were simultaneously recorded by continuous beat-to-beat non-invasive BP monitoring and transcranial Doppler at supine and orthostatic positions twice, before and after ALCT. The patients were divided into two groups according to those with increased and decreased CBF at baseline after ALCT to analyse the influencing factors. RESULTS: We examined 64 patients with PD (59.2 ± 11.6 years, 33 males). BP decreased at all timepoints after ALCT, while there was no significant change in the magnitude of the drop in BP induced by standing. CBF was reduced after ALCT, especially within 15 s to 1 min of standing (15 s: 48.95 ± 13.50 vs. 44.93 ± 13.26, p < 0.001; 30 s: 52.46 ± 12.06 vs. 50.11 ± 12.56, p = 0.033; 1 min: 52.19 ± 11.83 vs. 50.17 ± 13.21, p = 0.044). Lower body mass index (ß = -0.280, p = 0.027) was an independent factor associated with CBF reduction after ALCT. CONCLUSIONS: Additional attention should be paid to changes in CBF and BP within 1 min after standing in patients with PD taking levodopa, especially in those with low bodyweight.

The differences of orthostatic hypotension in patients with Parkinson's disease and multiple system atrophy.

Background: Multiple system atrophy (MSA) and Parkinson's disease (PD) have similar clinical presentations in their early stages. Orthostatic hypotension (OH) is a common autonomic dysfunction associated with MSA and PD. Heart rate (HR) and systolic blood pressure (SBP) changes are measured in response to the active standing test, which is widely used to screen for cardiovascular autonomic function. Objectives and methods: Overall, 255 patients (67 MSA, 188 PD) underwent continuous beat-to-beat non-invasive BP monitoring and active standing test. The total standing time was 10 min, and the BP differences between both groups were compared to determine whether the ΔHR/ΔSBP can differentiate both conditions. Results: Classical orthostatic hypotension (COH) (52%) and initial OH (19%) were most common in MSA and PD, respectively. MSA had a higher HR (75.0 ± 9.7 vs. 71.0 ± 10.7, P = 0.008) than PD in the supine position. SBP (135.70 ± 15.68 mmHg vs. 127.31 ± 15.14 mmHg, P = 0.106), diastolic BP (78.45 ± 12.36 mmHg vs. 67.15 ± 13.39 mmHg, P = 0.009) and HR (73.94 ± 8.39 bpm vs. 71.08 ± 13.52 bpm, P = 0.389) at baseline were higher in MSA-COH than in PD-COH. After adjusting for age and disease duration, the ΔHR/ΔSBP-10 min significantly discriminated MSA-COH from PD-COH (P = 0.031). An ΔHR/ΔSBP-10 min of 0.517 showed a sensitivity of 67% and specificity of 84% (AUC = 0.77, 95% CI: 0.63-0.91). Conclusion: The SBP, diastolic BP, and HR were higher in the supine position; however, ΔHR and ΔSBP were lower after standing in MSA patients than in PD patients. The ΔHR/ΔSBP-10 min discriminated between MSA-COH and PD-COH with quiet acceptable accuracy.

The mechanism of impaired delayed recall verbal memory function in Parkinson's disease with orthostatic hypotension: a multiple imaging study.

Introduction: Orthostatic hypotension (OH) frequently accompanies autonomic dysfunction and is an important risk factor for cognitive impairment in Parkinson's disease (PD). However, the association between different cognitive functions and OH in PD patients is not yet fully understood. Methods: This study aimed to evaluate the scores of different cognitive domains and multiple parameters using different imaging techniques on PD patients with or without OH. A total number of 31 PD patients with OH (n = 20) and without OH (n = 11) were recruited from the Department of Neurology, Beijing Xuanwu Hospital for this study. All patients underwent beat-to-beat non-invasive blood pressure recordings and an active standing test to evaluate neurogenic OH and a global neuropsychological test to assess cognitive function. All patients underwent dynamic cerebral autoregulation (dCA) measurement, brain magnetic resonance imaging (MRI), and brain 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Results: The results showed that OH patients had poor delayed recall verbal memory when compared with the PD patients without OH (1.75 ± 1.59 vs. 3.10 ± 1.73, p = 0.042). The dCA test indicated a significant difference in the right very low-frequency (VLF) gain between two groups (1.27 ± 0.17 vs. 1.10 ± 0.26, p = 0.045) and the brain 18F-FDG PET/CT indicated a significant difference in the SUV (right medial temporal lobe) to SUV (occipital lobe) ratio (0.60 ± 0.08 vs. 0.67 ± 0.11, p = 0.049). Meanwhile, these two imaging parameters were negatively correlated (p < 0.001). Furthermore, the score of a delayed recall verbal memory in the OH group was positively correlated with the right medial temporal lobe to occipital lobe ratio (p < 0.001) and was negatively correlated with the right VLF gain (p = 0.023). Discussion: PD with OH patients had poor delayed recall memory, which might have been caused by the decreased metabolic dysfunction of specific medial temporal lobe due to the impaired dCA ability.

Tough all-polysaccharide hydrogels with uniaxially/planarly oriented structure.

Considering that the poor mechanical performances of polysaccharide hydrogels always limit their practical applications, herein, we design and fabricate tough all-polysaccharide hydrogels by incorporating uniaxially/planarly oriented tunicate cellulose nanocrystals in physically cross-linked alginate networks. Firstly, alginate chains were loosely cross-linked by surface quaternized tunicate cellulose nanocrystals (Q-TCNCs) and Ca2+ through electrostatic interaction. Secondly, the loosely cross-linked hydrogel was pre-stretched and immersed into CaCl2 solution, obtaining uniaxially oriented hydrogel, whose tensile strength was 31.6 MPa along the pre-stretching direction. After biaxial stretching, the orientation of TCNCs in hydrogel networks converted from dominantly uniaxially oriented structure to planarly oriented structure. The tensile strength, elastic modulus, and toughness of the planarly oriented hydrogels were about 6.6-, 44- and 3.3-folds of those of isotropic Q-TCNC/alginate hydrogel. This work provided a facile and efficient strategy for developing tough hydrogels with uniaxially/planarly oriented structure from biodegradable polymers.

Two cases of rt-PA with dual antiplatelet therapies with capsular warning syndrome.

RATIONALE: Capsular warning syndrome (CWS) is a term to describe stereotyped lacunar transient ischemic attacks (TIAs). Patients with CWS are at high risk of developing completed stroke. However, the exact pathophysiology of CWS is still unclear, and there is no conclusive clinical strategy for CWS patients. PATIENT SYMPTOMS: Two cases of middle-aged men with hypertension, hyperlipidemia, and diabetes mellitus presented with fluctuating right-sided weakness, numbness, and dysarthria. DIAGNOSES: These two patients were diagnosed with CWS. INTERVENTIONS: Recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis (0.9 mg/kg) was administered first and treated with aspirin (100 mg) and clopidogrel (75 mg) after 24 h of rt-PA for 21 days following by aspirin (100 mg) alone. OUTCOMES: Both cases got favorable clinical outcomes of somatic symptoms. In addition, diffusion-weighted imaging (DWI or DW-MRI) showed that ischemic injury disappeared in case 1 while maintained within a reasonable range in case 2. LESSONS: Early recognition and rt-PA/dual antiplatelet treatment may be an effective strategy for patients with CWS.

Microstructural changes in the cingulate gyrus of patients with mild cognitive impairment induced by cerebral small vessel disease.

Objective: The purpose of our study was to distinguish the changes in the microstructure of the cingulate cortex in patients with mild cognitive impairment (MCI) induced by cerebral small vessel disease (CSVD).Method: 80 patients were diagnosed with CSVD in this study, including 55 patients with MCI and 25 patients without MCI. Diffusion kurtosis imaging (DKI) and Montreal cognitive assessment (MoCA) were performed in all patients. The anterior cingulate gyrus, posterior cingulate gyrus and middle cingulate gyrus were selected as the regions of interest, and some parameters were recorded.Results: Compared with the non-MCI group, the MCI group mainly showed obviously higher mean diffusion (MD) and radial diffusion (RD) values (P = 0.022 and P = 0.029) but lower fractional anisotropy (FA), axial kurtosis (AK), mean kurtosis (MK) and radial kurtosis (RK) values (P = 0.047, P = 0.001, P < 0.01, and P = 0.001, respectively) in the right anterior cingulate gyrus. Meanwhile, in the right posterior cingulate gyrus, the MCI group also showed higher axial diffusion (AD) and MD (P = 0.027 and P = 0.030) and lower AK (P = 0.014). Additionally, negative correlations of AD, MD, and RD with MoCA scores and positive correlations of FA, AK, MK and RK with MoCA scores were observed in some regions of the cingulate gyrus.Conclusions: DKI is a good method to examine microstructural damage in the cingulate cortex, and some parameters of DKI may be used as imaging biomarkers to detect early MCI in patients with CSVD.

Association between the SORL1 rs2070045 polymorphism and late-onset Alzheimer's disease: interaction with the ApoE genotype in the Chinese Han population.

Late-onset Alzheimer's Disease (LOAD) is a common neurodegenerative disease [1], and the two well identified pathological hallmarks of LOAD are senile plaques formed from amyloid ß peptides (Aß) and neurofibrillary tangles (NFTs) consisting of hyperphorylated tau protein [2]. The neuronal Sortilin-related receptor (SORL1) is involved in the processing and trafficking of amyloid precursor protein (APP) into recycling pathways, thus influencing Aß generation and by this AD pathology [3]. To explore the relationship between the single nucleotide polymorphism (SNP) of the SORL1 SNP 19 rs2070045 and LOAD, a case-control study was conducted in a Chinese Han cohort including 77 LOAD patients and 100 control participants. This SNP 19 rs2070045 was genotyped with a polymerase chain reaction-restriction fragment length polymorphism, (PCR-RFLP) method. The association was revealed between the polymorphism of SNP 19 rs2070045 (T/T, T/G, G/G) and the risk of LOAD. The results of this study indicated that the T allele (T/G+T/T) of SNP 19 rs2070045 was successful in exerting obvious influence in LOAD patients (χ(2)=4.884, P=0.027<0.05). However, there is no sufficient evidence to prove that the T allele of SNP 19 rs2070045 is associated with ɛ4 allele of ApoE gene in LOAD patients (χ(2)=0.771, P=0.380>0.05).