Efficacy of Poria Cocos Extract on Sleep Quality Enhancement: A Clinical Perspective with Implications for Functional Foods.

BACKGROUND: Since the outbreak of the pandemic started, an increase in the number of sleep disorders, including insomnia and poor sleep quality, has been seen. The pattern will probably continue. METHODS: This study focuses on the preparation and clinical testing of Poria cocos extract in treating suboptimal sleep quality. The optimal extraction method utilized a 75% ethanol concentration, and the clinical investigation involved subjects with defined poor sleep taking 800 mg of the extract nightly, assessed using the Sleep Questionnaire and polysomnography. The non-parametric Wilcoxon signed-rank test was used for statistical analysis due to the non-normal distribution of the collected data. RESULTS: The study involved 21 insomnia sufferers with a mean age of 55 who were administered Poria cocos extracts. The findings of the study indicate a statistically significant rise in the overall duration of sleep (from 327.395 ± 43.2 min to 356.516 ± 63.21 min, p = 0.014). Additionally, there was a notable decrease in the level of arousal during sleep (from 76.316 ± 44.78 min to 47.989 ± 42.38 min, p = 0.009), and an improvement in the sleep severity index of the sleep questionnaire test. CONCLUSIONS: Poria cocos as a natural substance could improve quality of sleep, based on the findings. The study investigates Pachymic acid, a substance found in Poria cocos, as a potential indicator for the development of sleeping aids.

Application of Static Headspace GC-MS Method for Selective 1,4-Dioxane Detection in Food Additives.

Efficient detection methods must be developed for 1,4-dioxane due to its suspected status as a human carcinogen, which is highly mobile in food and environmental resources. In this regard, this experiment has been conducted to develop reliable and selective detection and measurement methods by using static headspace (SH) isolation, followed by gas chromatography-mass spectrometry (GC-MS). A new method was developed for determining the spiked 1,4-dioxane contents in a polyethylene glycol 600 (PEG 600). The optimal condition for SH-GC-MS was discussed. The representative ions of 1,4-dioxane and 1,4-dioxane-d8 in the SIM mode of MS are 88 and 96, respectively, and the peaks of the SIM mode were separated and confirmed. The linear range for the method covers 0.25 to 100 mg/L with a coefficient of determination (R2) ≥ 0.999. The method applicability was demonstrated by spike recovery across a variety of food additives (i.e., chlorine bitartrate, choline chloride, polysorbate 20 and 60, and PEG 1000). All spike recovery from the tested samples was in the range of 89.50-102.68% with a precision of 0.44-11.22%. These findings suggest a new analytical method for food safety inspection, and could be applicable for ensuring the safety of foods and environmental and public health on a broad scale.

Efficacy and safety of oxiracetam in patients with vascular cognitive impairment: A multicenter, randomized, double-blinded, placebo-controlled, phase IV clinical trial.

BACKGROUND: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022. CONCLUSION: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).

The Positive Effects of Poria cocos Extract on Quality of Sleep in Insomnia Rat Models.

Sleep disorders may have various causes and can incur mental and/or physical symptoms, and affect an individual's quality of life. In this study, we confirm that the Poria cocos extract (PCET) can improve sleep quality and structure by promoting inhibitory neurotransmission via the γ-aminobutyric acid (GABA) type A (GABAA) receptors based on the mechanisms revealed in the experiment with superior cervical ganglion neurons. Pentobarbital-induced sleep tests were conducted in order to determine whether the PCET extract improves the sleep quality and structure in normal ICR mice. Sleep latency and duration were checked with the righting reflex. To simulate the state of awakening as well as a normal sleep state, caffeine was administered orally before the PCET diet. After oral gavage of PCET, sleep latency was decreased, and total sleep duration was increased in normal and caffeine-induced sleep disturbance state. In the ACTH-induced sleep disturbed models, administration of PCET significantly reduced the sleep latency and increased the non-REM sleep duration, which was analyzed in real-time EEG by implanting wireless electrodes in SD rats. PCET was found to improve the sleep quality under a normal sleep state through the GABAA receptor; it also promoted and improved the sleep quality and sleep structure in both the arousal activation state and stress-based sleep disturbance.

Predictive value of the videofluoroscopic swallowing study for long-term mortality in patients with subacute stroke.

ABSTRACT: To investigate the usefulness of the videofluoroscopic swallowing study (VFSS) for subacute stroke in predicting long-term all-cause mortality, including not only simple parameters obtained from VFSS results, but also recommended dietary type as an integrated parameter.This was a retrospective study of patients with subacute (<1 month) stroke at a university hospital between February 2014 and September 2019. The independent risk factors were investigated using stepwise Cox regression analysis, which increased the all-cause mortality of patients with stroke among VFSS parameters.A total of 242 patients with subacute stroke were enrolled. The significant mortality-associated factors were age, history of cancer, recommended dietary type (modified dysphagia diet; adjusted hazard ratio [HR], 6.971; P = .014; tube diet, adjusted HR: 10.169; P = .019), and Modified Barthel Index. In the subgroup survival analysis of the modified dysphagia diet group (n = 173), the parameters for fluid penetration (adjusted HR: 1.911; 95% confidence interval, 1.086-3.363; P = .025) and fluid aspiration (adjusted HR: 2.236; 95% confidence interval, 1.274-3.927; P = .005) were significantly associated with mortality.The recommended dietary type determined after VFSS in subacute stroke was a significant risk factor for all-cause mortality as an integrated parameter for dysphagia. Among the VFSS parameters, fluid penetration and aspiration were important risk factors for all-cause mortality in patients with moderate dysphagia after stroke. Therefore, it is important to classify the degree of dysphagia by performing the VFSS test in the subacute period of stroke and to determine the appropriate diet and rehabilitation intervention for mortality-related prognosis.

Significantly Reduced Alanine Aminotransferase Level Increases All-Cause Mortality Rate in the Elderly after Ischemic Stroke.

(1) Background: A significantly reduced alanine aminotransferase (ALT) level is being recognized as a risk factor of increasing mortality in the elderly in relation to frailty. In the elderly, both frailty and ischemic stroke are not only common, but are also associated with mortality. The aim of this research was to investigate whether a significantly reduced ALT level increases the all-cause mortality rate in the elderly with ischemic stroke. (2) Methods: Between February 2014 and April 2019, a retrospective study of 901 patients with ischemic stroke admitted to a university-affiliated hospital was conducted. Cox proportional hazard regression was used to determine whether a significantly reduced ALT level is an independent risk factor for mortality in elderly patients after an ischemic stroke. (3) Results: This study enrolled 323 older adults (age ≥ 65 years) who were first diagnosed with ischemic stroke. The mean age of the participants was 76.5 ± 6.6 years, the mean survival time was 37.1 ± 20.4 months, and the number of deaths was 96 (29.7%). Our results showed that reduced ALT level (less than 10 U/L) increased the risk of all-cause mortality in the elderly after ischemic stroke (adjusted HR: 3.24, 95% CI: 1.95-5.41; p < 0.001). (4) Conclusions: A significantly reduced ALT level at the time of diagnosis (less than 10 U/L) is an independent risk factor that increases the mortality rate in the elderly after ischemic stroke.

The Association between Nonalcoholic Fatty Liver Disease and Stroke: Results from the Korean Genome and Epidemiology Study (KoGES).

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is associated with various cardiometabolic diseases. However, the association between NAFLD and stroke is not well known. The purpose of our study is to reveal the relationship between NAFLD and Stroke incidence. (2) Methods: Using data from a Korean prospective cohort study, we excluded participants with heavy alcohol consumption and a history of stroke; hence, 7964 adults aged 40-69 years were included in this study. According to their fatty liver index (FLI), participants were divided into three groups: <30 (n = 4550, non-NAFLD), 30-59.9 (n = 2229, intermediate), and ≥60 (n = 1185, NAFLD). The incidence of stroke according to the degree of FLI was evaluated using the Cox proportional hazard model. (3) Results: During the 12-year follow-up period, 168 strokes occurred. A graded association between NAFLD and stroke incidence was observed, i.e., 1.7% (n = 76), 2.5% (n = 56), and 3.0% (n = 36) for non-NAFLD, intermediate, and NAFLD FLI groups, respectively. After adjusting for confounding variables and compared to the risk of stroke in the non-NAFLD group, the risk of stroke in the NAFLD group was the highest (hazard ratio [HR]: 1.98, 95% confidence interval [CI]: 1.17-3.34), followed by the risk of stroke in the intermediate group (HR: 1.41, 95% CI: 0.94-2.21) (p for trend < 0.001). However, the level of aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyltransferase alone did not show any significant association with stroke. (4) Conclusions: This study demonstrated that the risk of stroke incidence gradually increased with the degree of FLI. Individuals with NAFLD should be properly counseled and monitored for risk for stroke.

The Impact of Time-Restricted Diet on Sleep and Metabolism in Obese Volunteers.

Background and objectives: A time-restricted diet is one of the various ways to improve metabolic condition and weight control. However, until now, there have been few pieces of evidence and research to verify the methods and effectiveness of time-restricted diets on metabolic improvement and health promoting. We designed this study to make a healthy diet program and to verify the effectiveness of a time-restricted diet on general health, including sleep and metabolism, in healthy volunteers. Materials and Methods: This study was conducted in healthy adults who are obese but do not have related metabolic disease. Fifteen participants were recruited. Before and after this program, serologic tests including ketone level, questionnaires-daytime sleepiness evaluation such as the Epworth sleepiness scale and the Stanford sleepiness scale, the Korean version of the Pittsburgh sleep questionnaire index, STOP BANG to evaluate sleep apnea, the Hospital Anxiety and Depression Scale for emotion/sleep-and polysomnography (PSG) were conducted to evaluate the effects on sleep of the program. They were divided into two groups based on ketone levels that could reflect the constancy of participation in this study. We analyzed the before and after results of each group. Results: Fifteen participants (nine males and six females) completed this program without significant adverse events. Body weight after this program decreased to 78.2 ± 14.1 from 82.0 ± 15.6 kg (p = 0.539), and BMI decreased to 27.9 ± 3.8 from 29.3 ± 4.6 kg/m2 (p = 0.233). Weight loss was observed in 14 subjects except 1 participant. The results from questionnaires before and after this were not significant changes. They were classified into high/low-ketone groups according to the ketone level of the participants. In the results of the PSG, the apnea hypopnea index (25.27 ± 12.67→15.11 ± 11.50/hr, p = 0.25) and oxygen desaturation (18.43 ± 12.79→10.69 ± 10.0/hr, p = 0.004), which are indicators of sleep apnea, also improved in the high-ketone group, compared with the low-ketone group. Satisfaction interviews for this restricted diet program showed that 86% of the participants were willing to participate in the same program again. Conclusion: The time-restricted diet was successful in weight loss for a period of 4 weeks in obese participants, which did not affect the efficiency and architecture of sleep. In addition, successful weight loss and significant improvement of sleep apnea were showed in the high-ketone group. Further research is needed to demonstrate mechanisms for weight loss, sleep apnea, and time-restricted diets.

Effect of Forest Therapy for Menopausal Women with Insomnia.

Female hormone changes during menopause can affect the autonomic nervous system, circadian rhythm, and secretion of cortisol/melatonin, resulting in a vulnerability to insomnia. In this light, therapy has been gaining attention as a way to reduce stress hormones by stabilizing the autonomic nervous system. Thus, this study aims to objectively and scientifically analyze the impact of forest therapy in postmenopausal insomnia patients. The forest therapy program lasted 6 days, wherein 35 postmenopausal women performed activities such as trekking, leg massages, stretches, and bathing in warm and cold water. They also underwent serologic tests, participated in polysomnography (PSG), and answered sleep questionnaires before and after the program. Further, a statistical analysis compared the results. Serologic tests showed a significant reduction of cortisol from 10.2 ± 3.79 to 7.75 ± 2.81, while PSGs showed how sleep efficiency increased to 89.3 ± 4.3% (p < 0.01), and how waking after sleep onset reduced to 47.4 ± 22.3 min (p < 0.01). The total sleep time also increased to 428.5 min and sleep latency was 11.1 ± 11.0 min. Despite its limitations, forest therapy could be a good alternative to nonpharmacological treatment for mitigating insomnia in postmenopausal women.

An Exploratory Study on the Effects of Forest Therapy on Sleep Quality in Patients with Gastrointestinal Tract Cancers.

The improvement of sleep quality in patients with cancer has a positive therapeutic effect on them. However, there are no specific treatment guidelines for treating sleep disturbance in cancer patients. We investigated the effect of forest therapy on the quality of sleep in patients with cancer. This study was conducted on nine patients (one male, eight female; mean age, 53.6 ± 5.8 years) with gastrointestinal tract cancer. All patients participated in forest therapy for six days. They underwent polysomnography (PSG) and answered questionnaires on sleep apnea (STOP BANG), subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI), sleepiness (Stanford and Epworth Sleepiness Scales), and anxiety and depression (Hospital Anxiety and Depression Scale) to evaluate the quality of sleep before and after forest therapy. Sleep efficiency from the PSG results was shown to have increased from 79.6 ± 6.8% before forest therapy to 88.8 ± 4.9% after forest therapy (p = 0.027) in those patients, and total sleep time was also increased, from 367.2 ± 33.4 min to 398 ± 33.8 min (p = 0.020). There was no significant difference in the STOP BANG score, PSQI scores, daytime sleepiness based on the results of the Stanford and Epworth Sleepiness Scales, and depression and anxiety scores. Based on the results of this study, we suggest that forest therapy may be helpful in improving sleep quality in patients with gastrointestinal cancers.

Unblinded, randomized multicenter trial comparing lamotrigine and valproate combination with controlled-release carbamazepine monotherapy as initial drug regimen in untreated epilepsy.

PURPOSE: To compare controlled-release carbamazepine monotherapy (CBZ-CR) with lamotrigine and valproate combination therapy (LTG + VPA) in equivalent total drug load, as initial drug regimen in untreated patients with partial and/or generalized tonic-clonic seizures (GTCS). METHODS: This unblinded, randomized, 60-week superiority trial recruited patients having two or more unprovoked seizures with at least one seizure during previous three months. After randomization into CBZ-CR or LTG + VPA, patients entered into eight-week titration phase (TP), followed by 52-week maintenance phase (MP). Median doses of CBZ-CR and LTG + VPA were 600 mg/day and 75 mg/day + 500 mg/day, respectively. Primary outcome measure was completion rate (CR), a proportion of patients who have completed the 60-week study as planned. Secondary efficacy measures included seizure-free rate (SFR) for 52-week of MP and time to first seizure (TTFS) during MP. RESULTS: Among 207 randomized patients, 202 underwent outcome analysis (104 in CBZ-CR, 98 in LTG + VPA). CR was 62.5% in CBZ-CR and 65.3% in LTG + VPA (p = 0.678). SFR during MP was higher in LTG + VPA (64.1%) than CBZ-CR (47.8%) (P = 0.034). TTFS was shorter with CBZ-CR (p = 0.041). Incidence of adverse effects (AEs) were 57.7% in CBZ-CR and 60.2% in LTG + VPA and premature drug withdrawal rates due to AEs were 12.5% and 7.1%, respectively, which were not significantly different. CONCLUSION: CR was comparable between LTG + VPA and CBZ-CR, however, both SFR for 52-week MP and TTFS during MP were in favor of LTG + VPA than CBZ-CR. The study suggested that LTG + VPA can be an option as initial drug regimen for untreated patients with partial seizures and/or GTCS except for women of reproductive age.

Efficacy and safety of stem cell therapies for patients with stroke: a systematic review and single arm meta-analysis.

BACKGROUND AND OBJECTIVES: Stem cell-based therapy is a potential new approach in the treatment of stroke. However, the efficacy and safety of these treatments are not yet fully understood. Therefore, we performed a meta-analysis of available single-arm studies using stem cell-based therapy in patients with stroke. METHODS: We searched MEDLINE, EMBASE, and the Cochrane database for studies of stem cell therapy in patients with stroke from its inception through July 2014. The articles included in the search were restricted to the English language, studies with at least 5 patients, and those using cell-based therapies for treating stroke. RESULTS: Fourteen studies included in the meta-analysis. The pooled mean difference in National Institutes of Health Stroke Scale (NIHSS) scores from baseline to follow-up points was 5.7 points (95%CI: -8.2 to -3.2, I(2) =91.5%) decreased. Also the pooled mean difference in modified Bathel index (BI) score was increased by 31.5 points (95%CI: 35.6∼14.9, I(2) =52.7%) and the pooled incidence rate to achieve on modified Rankin score (mRS)≤2 was 40% (95% CI: 30%∼51%, I(2) =35.4%) at follow-up points. The pooled incidence rates of death, seizure, and infection were 13% (95%CI, 8∼23%), 15% (95%CI, 8∼25%), and 15% (95%CI, 8∼23%), respectively. CONCLUSIONS: The published data suggest that stem cell-based therapy for patients with stroke can be judged as effective based on single arm clinical studies. However, clinical benefits of stem cell therapy for patients with stroke need further investigation and reevaluation to test the clinical efficacy.

Nighttime blood pressure and white matter hyperintensities in patients with Parkinson disease.

Increasing evidence indicates that nocturnal blood pressure level and/or loss of nocturnal blood pressure dips are sensitive markers of cardiovascular morbidity and mortality. Several studies have suggested that blunted heart rate variability and nocturnal decline in heart rate are also associated with target organ damage. These phenomena occur relatively commonly in patients with Parkinson disease (PD); however, few studies have assessed the consequences of these abnormalities in patients with PD. We investigated the influence of circadian changes in blood pressure and heart rate on white matter hyperintensities (WMHs) in patients with PD. The presence of nocturnal hypertension was associated with increased WMH score, and nighttime systolic pressure was closely related with white matter changes. Blunted heart rate variability and nocturnal decline in heart rate were also related to increasing WMH scores. The non-dipping phenomenon did not influence WMHs. These findings suggest that white matter changes are related to circadian autonomic dysfunction, particularly nocturnal hypertension in patients with PD. Therefore, it is important to monitor nocturnal blood pressure status, because modifying these circadian regulatory disturbances can be beneficial to protect against vascular brain damage in patients with PD.

The effect of levetiracetam on status epilepticus-induced neuronal death in the rat hippocampus.

PURPOSE: Levetiracetam has been reported to be well tolerated and effective in status epilepticus (SE) refractory to benzodiazepine. Because of little preclinical or clinical data concerning the outcomes of LEV in SE-induced neuronal death and vasogenic edema, we investigated the effect of LEV on SE-induced injury in comparison to diazepam (DZP), and valproate (VPA). METHODS: Two hours after pilocarpine-induced SE, rats were given one of the following drugs; (1) DZP, (2) LEV, (3) VPA, (4) DZP+LEV, (5) DZP+VPA, and (6) DZP+oxiracetam. Three-four days after SE, neuronal damage and vasogenic edema were evaluated by Fluoro-Jade B (FJB) staining and serum-protein extravasation, respectively. RESULTS: LEV (≥50 mg/kg) was effective to protect neuronal damage from SE in comparison to DZP and VPA. LEV as an add-on drug with DZP could not alleviate neuronal damage as compared to LEV alone. VPA (≥100 mg/kg) was effective to protect neuronal damage from SE, as compared to DZP. VPA as an add-on drug with DZP reduced neuronal damage, as compared to DZP alone. CONCLUSION: These findings suggest that LEV may negatively interact with DZP, and be more effective to prevent SE-induced neuronal death as a first line drug than as a second line therapy after BDZ treatment.

Combined use of ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter (DAT) positron emission tomography (PET) predicts prognosis in drug-induced Parkinsonism (DIP): a 2-year follow-up study.

DIP is a heterogeneous clinical syndrome; some patients develop persistent and worsening of parkinsonian symptoms after discontinuation of the offending drug, or Parkinson's disease (PD) reappears later after a full remission from DIP. However, it is difficult to predict the prognosis in patients with DIP. Herein, we evaluated whether the combined use of (18)F-N-(3-fluoropropyl)-2 beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET and cardiac MIBG scintigraphy can be used to help distinguish the prognosis in patients with DIP. Among 20 patients enrolled, 16 showed normal DAT uptake and normal myocardial sympathetic innervation. After withdrawal of the suspected drugs, the patients experienced a clinical remission of parkinsonian motor symptoms within 3 months and did not experience any new movement symptoms after at least 2 years of follow-up. Two patients with a moderate decrease in DAT uptake and impaired sympathetic denervation showed worsening of motor manifestations 3 months after discontinuation of the drugs. Another two patients with normal DAT uptake and decreased MIBG uptake, presented full remission of motor symptoms within 2 months after discontinuation of the drugs. However, these two patients eventually developed parkinsonism within 2 years of the follow-up period. The follow-up scans revealed severe decreased DAT uptake in the putamen and similar ranges of cardiac sympathetic denervation. The results suggest that the combined use of these techniques can predict the prognosis of DIP and suggest a proper therapeutic plan for DIP.

Low bone mineral density is associated with poor clinical outcome in acute ischemic stroke.

BACKGROUND: Chronic low bone mineral density is associated with an increased risk of stroke. However, little is known about the influence of bone mineral density at the time of stroke on clinical outcome. We investigated the association between bone mineral density and functional disability at three-months in patients with acute ischemic stroke. METHODS: We retrospectively examined consecutive acute ischemic stroke patients who underwent bone densitometry tests within seven-days of stroke symptom onset. Patient demographics, risk factors, and initial National Institute of Health Stroke Scale scores were assessed. Bone mineral density was measured at the lumbar spine and bilateral femoral necks. Osteoporosis was defined as bone mineral density ≤-2·5 T-scores at each site. The primary outcome was modified Rankin Scale at 90 days poststroke. A favorable outcome was defined as modified Rankin Scale 0-1 and poor outcome as modified Rankin Scale 2-6. RESULTS: Of the 191 patients included, 61 (31·9%) were men. Mean age (±standard deviation) was 69·8 ± 11·1 years. Patients with osteoporosis of the right femoral neck were more likely to have poor outcome (25/82; 30·5%) than those without (12/109; 11·0%, P = 0·001). After adjustment for age, sex, and initial National Institute of Health Stroke Scale score, osteoporosis of the right femoral neck was significantly associated with poor outcome (odds ratio, 2·97; 95% confidence interval 1·21 to 7·32, P = 0·018). CONCLUSIONS: Low bone mineral density of the right femur in the acute poststroke period is associated with poor outcome at three-months. Assessment of bone mineral density in acute stroke patients may be a useful prognosticator and facilitate early intervention.

Orthostatic hypotension, non-dipping and striatal dopamine in Parkinson disease.

Orthostatic hypotension and non-dipping are relatively common autonomic dysfunctions in patients with Parkinson disease (PD). These abnormalities have been thought to occur independently of striatal dopaminergic depletion; however, only little preliminary information is available. In this study, we investigated the association of neurocirculatory changes with striatal dopamine transporter status in 69 patients with early PD. Seventeen patients had orthostatic hypotension and 55 patients were non-dippers. A comparison between cases with and without orthostatic hypotension was insignificant for striatal dopamine transporter uptake. These insignificances continued in a comparison of dippers and non-dippers. These results suggest that sympathetic noradrenergic dysfunctions in PD are independent of striatal dopamine transporter depletion.

Anorectal manometric dysfunctions in newly diagnosed, early-stage Parkinson's disease.

BACKGROUND AND PURPOSE: Anorectal dysmotility is common in advanced Parkinson's disease (PD), but there have been few evaluations in newly diagnosed PD patients. METHODS: We conducted anorectal manometric evaluations in 19 newly diagnosed, drug-naïve, early-stage PD patients. All of the PD patients were questioned regarding the presence of anorectal symptoms. RESULTS: Anorectal manometry was abnormal in 12 of the 19 patients. These abnormalities were more common in patients with more severe anorectal symptoms, as measured using a self-reported scale. However, more than 40% of patients with no or minimal symptoms also exhibited manometric abnormalities. CONCLUSIONS: These results suggest that anorectal dysmotility manifests in many early-stage PD patients, which this represent evidence for the involvement of neuronal structures in such nonmotor manifestations in PD.

Association of cognitive dysfunction with neurocirculatory abnormalities in early Parkinson disease.

OBJECTIVE: Cognitive impairment and neurocirculatory abnormalities such as orthostatic hypotension (OH), supine hypertension (SH), and failure to decrease blood pressure at night (nondipping) occur relatively commonly in Parkinson disease (PD); however, whether cognitive dysfunction in early PD is related to neurocirculatory abnormalities has not been established. Cognitive dysfunction in PD is associated with white matter hyperintensities on MRI. We report results of an analysis of neuropsychological and hemodynamic parameters in patients with early PD. METHODS: Among 87 patients, 25 had normal cognition, 48 had mild cognitive impairment, and 14 had dementia, based on comprehensive neuropsychological tests. Orthostatic vital signs and ambulatory 24-hour blood pressure monitoring were recorded, and brain magnetic resonance scans were obtained for all patients. RESULTS: Cognitive impairment was associated with OH, SH, and white matter hyperintensities but not with nondipping. Dementia and white matter hyperintensities were common in SH. Of 13 patients with OH + SH, every one had mild cognitive impairment or dementia. CONCLUSIONS: Cognitive dysfunction is related to neurocirculatory abnormalities, especially OH + SH, in early PD, raising the possibility that early detection and effective treatment of those abnormalities might slow the rate of cognitive decline.

Changes in glucose metabolism and metabolites during the epileptogenic process in the lithium-pilocarpine model of epilepsy.

PURPOSE: The metabolic and biochemical changes that occur during epileptogenesis remain to be determined. (18) F-Fluorodeoxyglucose positron emission tomography (FDG-PET) and proton magnetic resonance spectroscopy ((1) H MRS) are noninvasive techniques that provide indirect information on ongoing pathologic changes. We, therefore, utilized these methods to assess changes in glucose metabolism and metabolites in the rat lithium-pilocarpine model of epilepsy as markers of epileptogenesis from baseline to chronic spontaneous recurrent seizures (SRS). METHODS: PET and MRS were performed at baseline, and during the acute, subacute, silent, and chronic periods after lithium-pilocarpine induced status epilepticus (SE). Sequential changes in glucose metabolism on (18) F-FDG PET using SPM2 and the ratios of percent injected dose per gram (%ID)/g of regions of interest (ROIs) in the bilateral amygdala, hippocampus, basal ganglia with the thalamus, cortex, and hypothalamus normalized to the pons were determined. Voxels of interest (VOIs) on (1) H MRS were obtained at the right hippocampus and the basal ganglia. NAA/Cr levels and Cho/Cr at various time points were compared to baseline values. KEY FINDINGS: Of 81 male Sprague-Dawley rats, 30 progressed to SRS. (18) F-FDG PET showed widespread global hypometabolism during the acute period, returning to baseline level during the subacute period. Glucose metabolism, however, declined in part of the hippocampus during the silent period, with the hypometabolic area progressively expanding to the entire limbic area during the chronic period. (1) H MRS showed that the NAA/Cr levels in the hippocampus and basal ganglia were reduced during the acute period and were not restored subsequently from the subacute to the chronic period without any significant change in the Cho/Cr ratio throughout the entire experiment. SIGNIFICANCE: Serial metabolic and biochemical changes in the lithium-pilocarpine model of epilepsy indirectly represent the process of human epileptogenesis. Following initial irreversible neural damage by SE, global glucose metabolism transiently recovered during the subacute period without neuronal recovery. Progressive glucose hypometabolism in the limbic area during the silent and chronic periods may reflect the important role of the hippocampus in the formation of ongoing epileptic network during epileptogenesis.